PATENT DOCUMENT

Abstract:
The present invention relates to a method for selecting an anti-herpes viral compound and a method for selectively inhibiting herpesvrus in a human host in need of such treatment.  
     The present invention relates to a method for selecting an anti-herpes viral compound and a method for selectively inhibiting herpesvrus in a human host in need of such treatment.

Full Description:
CROSS REFERENCE  
       [0001]    This application claims the benefit of the following provisional applications: U.S. Ser. No: 60/218,118, filed Jul. 13, 2000; Ser. No: 60/283,880, filed Apr. 13, 2001 under 35 USC 119(e)(i). 
     
    
     
       FIELD OF THE INVENTION  
         [0002]    The present invention relates to a method for selecting an anti-herpes viral compound and a method for selectively inhibiting herpes viruses in a human host in need of such treatment.  
         BACKGROUND OF THE INVENTION  
         [0003]    The herpesviruses comprise a large family of double stranded DNA viruses. Eight of the herpes viruses, herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and human herpes viruses 6, 7, and 8 (HHV-6, HHV-7, and HHV-8), have been shown to infect humans. Several of these viruses are important human pathogens.  
           [0004]    HSV-1 is estimated to affect 100 million people in the U.S. Primary infection of HSV-1 usually occurs between the ages of one and four. Cold sores, the visible symptom, typically appear at a later age, with 20-45% of the population over the age of fifteen affected (Whitley, Clin. Intect. Dis., 26:541-555, 1998).  
           [0005]    Genital herpes (HSV-2) is the second most common sexually transmitted disease, with approximately 22% of the U.S population infected with this virus (Fleming 1997).  
           [0006]    VZV is the causative agent of chicken pox upon primary infection and can recur in adults as zoster.  
           [0007]    EBV results in approximately two million cases of infectious mononucleosis in the U.S. each year. It can also cause lymphomas in immunocompromised patients and has been associated with Burkitt&#39;s lymphoma, nasopharyngeal carcinoma, and Hodgkins disease.  
           [0008]    Infection with HCMV often occurs during childhood and is typically asymptomatic except in immunocompriomised patients where it causes significant morbidity and mortality.  
           [0009]    HHV-6 is the causitive agent of roseola and may be associated with multiple sclerosis and chronic fatigue syndrome. HHV-7 disease association is unclear, but it may be involved in some cases of roseola. HHV-8 has been associated with Karposi&#39;s sarcoma, body cavity based lymphomas, and multiple myeloma.  
           [0010]    These viruses are capable of residing in a latent state within the host. Reactivation of latent virus results from response to environmental stimuli (ex. UV exposure, stress, etc.). Infections or recurrence can be life threatening in immunocompromised patients such as AIDS or transplant patients where HCMV can result in retinitis, pneumonia, and gastrointestinal disease.  
           [0011]    The increased immunocompromised population has created an unmet medical need for antivirals against herpesviruses because current therapies do not have a sufficiently broad spectrum against this family of viruses and/or they have limited utility due to toxicity. The present invention provides a method for selectively inhibiting herpesviruses DNA polymerase with compounds that have broad spectrum activity. The method offers a distinct advantage in the treatment of patients in need, particularly immunocompromised patients at risk of infection or reactivation by many members of the herpesvirus family.  
         SUMMARY OF THE INVENTION  
         [0012]    The present invention provides a method of selecting compounds that inhibit herpes viruses comprising:  
           [0013]    a) measuring IC 50  of a compound of interest that inhibits a wild type herpes virus,  
           [0014]    b) measuring IC 50  of the same compound that inhibits a binding domain mutant herpes virus which is the same strain of the wild type herpes virus,  
           [0015]    c) comparing IC 50  of step a with IC 50  of step b; and  
           [0016]    d) selecting the compound of interest wherein the IC 50  of step b is at least 3 times greater than the IC 50  of step a.  
           [0017]    In above method, the order of step a and step b are interchangeable.  
           [0018]    The present invention further provides a method of selecting compounds that inhibit herpes viruses comprising:  
           [0019]    a) measuring IC 50  of a compound of interest that inhibits a wild type HSV-1,  
           [0020]    b) measuring IC 50  of the same compound that inhibits a binding domain mutant HSV-1 which is the same strain of the wild type herpes virus,  
           [0021]    c) comparing IC 50  of step a with IC 50  of step b; and  
           [0022]    d) selecting the compound of interest wherein the IC 50  of step b is at least 3 times greater than the IC 50  of step a.  
           [0023]    In above method, the order of step a and step b are interchangeable.  
           [0024]    The present invention further provides a method of selecting compounds that inhibit herpes viruses comprising:  
           [0025]    a) measuring IC 50  of a compound of interest that inhibits a wild type HSV-2,  
           [0026]    b) measuring IC 50  of the same compound that inhibits a binding domain mutant HSV-2 which is the same strain of the wild type herpes virus,  
           [0027]    c) comparing IC 50  of step a with IC 50  of step b; and  
           [0028]    d) selecting the compound of interest wherein the IC 50  of step b is at least 3 times greater than the IC 50  of step a.  
           [0029]    In above method, the order of step a and step b are interchangeable.  
           [0030]    The present invention further provides a method of selecting compounds that inhibit herpes viruses comprising:  
           [0031]    a) measuring IC 50  of a compound of interest that inhibits a wild type HCMV,  
           [0032]    b) measuring IC 50  of the same compound that inhibits a binding domain mutant HCMV which is the same strain of the wild type herpes virus,  
           [0033]    c) comparing IC 50  of step a with IC 50  of step b; and  
           [0034]    d) selecting the compound of interest wherein the IC 50  of step b is at least 3 times greater than the IC 50  of step a.  
           [0035]    In above method, the order of step a and step b are interchangeable.  
           [0036]    The present invention further provides a method for selectively treating diseases caused by herpes viruses in a human host comprising administering a compound to a human in need of such treatment wherein said compound inhibits herpes viruses by interaction with the binding domain in the viral DNA polymerase.  
           [0037]    The present invention further provides method for selectively inhibiting herpes viruses in a human host comprising administering a compound to a human in need of such treatment wherein IC 50  of the compound that inhibits a binding domain mutant herpes virus is at lease 3 times greater than IC 50  of the compound that inhibits a wild type herpes virus which is the same strain as the mutant herpes virus.  
           [0038]    The present invention further provides a compound for treating herpesviral infections in a human host wherein IC 50  of the compound that inhibits a binding domain mutant herpes virus is at lease 5 times greater than IC 50  of the compound that inhibits a wild type herpes virus which is the same strain as the mutant herpes virus.  
           [0039]    The present invention further provides a compound for treating herpesviral infections in a human host wherein said compound inhibits the herpesvirus by interacting with the binding domain in the viral DNA polymerase.  
           [0040]    The present invention further provides a compound for the inhibiting of herpesvirus DNA polymerases wherein serial passage of a wild type herpes virus in the presence of said compound results in a change of the wild type HSV-1 polymerase at amino acid 823 from valine to alanine.  
           [0041]    The present invention further provides a compound for inhibiting herpesvirus DNA polymerases wherein serial passage of a wild type herpes virus in the presence of said compound results a change of the wild type HCMV polymerase at amino acid 823 from valine to alanine and at amino acid 824 from valine to leucine.  
           [0042]    The present invention further provides a mutant herpesvirus DNA molecule having a nucleotide sequence selected from a group consisting of SEQ.ID.NO. 1; SEQ.ID.NO. 3; SEQ.ID.NO. 5; SEQ.ID.NO. 7; SEQ.ID.NO. 9; and SEQ.ID.NO. 11.  
           [0043]    The present invention further provides a mutant herpesvirus polymerase amino acid molecule having an amino acid sequence selected from a group consisting of SEQ.ID.NO. 2; SEQ.ID.NO. 4; SEQ.ID.NO. 6; SEQ.ID.NO. 8; SEQ.ID.NO. 10 and SEQ.ID.NO. 12. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0044]    [0044]FIG. 1—examples of 4-oxo-DHQ and 4-oxo-DHTP compounds.  
         [0045]    [0045]FIG. 2—Herpesvirus&#39; polymerases amino acid conserved region.  
         [0046]    [0046]FIG. 3—Recovered virus after serial passage of HSV-1 in presence of 20 μM of compound No. 17.  
         [0047]    [0047]FIG. 4—Comparision of Wild HSV-1 and HSV-2 herpesvirus DNA polymerase amino acid sequences alligned by amino acid homology. (Seq. No: 14-19)  
         [0048]    [0048]FIG. 5—Mutant Herpes Virus DNA and amino acid sequence list. (Seq. No: 1-12)  
         [0049]    [0049]FIG. 6—Wild HCMV herpesvirus DNA polymerases amino acid sequence. (Seq. No 13) 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0050]    A key enzyme in the replication of all herpesviruses is the virus-coded DNA polymerase. Most of the currently available anti-herpes drugs target the viral DNA polymerase. Drugs such as Foscarnet acts by direct inhibition of the viral polymerase. These drugs are non-nucleoside inhibitors of herpesvirus DNA polymerases. Others such as the nucleoside analogs, Acyclovir, Penciclovir and Ganciclovir must first be phosphorylated to the monophosphate forms by virus encoded kinases and, further phosphorylated to triphosphate by cellular enzymes before they are active inhibitors. The triphosphate forms of these nucleoside analogs inhibit polymerases by competing with the binding of natural triphosphates and their subsequent insertion into growing DNA strands. These drugs are known as nucleoside inhibitors of herpesvirus DNA polymerases.  
         [0051]    One of the limitations of the currently available drugs is that they are active against only a few of the eight human herpesviruses. For example, Acyclovir and Penciclovir inhibit HSV and VZV replication but have poor activity against CMV.  
         [0052]    In order to identify antiviral compounds that would have the potential to inhibit replication of most of the human herpesviruses, compounds are in vitro screened for inhibitors of herpesvirus DNA polymerase activity. Because portions of the amino acid sequence of the polymerases are highly conserved within the herpesvirus family it is possible to discover small molecules that inhibit herpesvirus polymerases but not cellular DNA polymerases. Using this biochemical approach, several new classes of compounds such as the 4-hydroxyquinoline derivatives (4-HQ), 4-oxo-dihydroquinoline derivatives (4-oxo-DHQ) and 4-oxo-dihydrothienopyridine derivatives (4-oxo-DHTP) were discovered as potent, non-nucleoside herpesvirus DNA polymerase inhibitors. In vitro polymerase assays and/or in vivo cell culture assays have demonstrated that these compounds inhibit HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-8 replication.  
         [0053]    4-Oxo-DHQ and 4-oxo-DHTP are derivatives of formula I  
                         
 
         [0054]    wherein ring A is a saturated or unsaturated fused double or triple heterocyclic ring having 1, 2, 3 or 4 heteroatoms selected from group consisting of oxygen, sulfur, or nitrogen; and wherein R and X are the appropriated substitutents, respectively.  
         [0055]    Examples of 4-HQ compounds, 4-oxo-DHQ compounds and 4-oxo-DHTP compounds are illustrated in FIG. 1.  
         [0056]    Antiviral activity of these examples are shown in Table 1 below. As shown in Table 1, these compounds inhibit HSV-1 and HSV-2 as well or better than the current commercially available drug Acyclovir.  
                                                                                         TABLE 1                           Antiviral Activity of 4-oxo DHQ/4-oxo DTHP Against HSV-1 and HSV-2                Compound IC 50  (uM)                virus   1   2   3   4   5   ACV                    HSV-1 KOS   2.0   3.8   3.2   3.2   3.3   3.6       HSV-1 F   2.5   2.3   2.2   2.1   2.6   1.3       HSV-1 DJL   2.5   2.6   1.8   2.2   2.7   1.8       HSV-1 Patton   ND   5.3   7.7   4.3   10   9.3       HSV-2 MS   2.0   2.5   2.8   2.5   2.5   10       HSV-2 35D   ND   5.4   5.0   3.2   8.1   6.0       HSV-2 186   2.0   2.3   3.2   2.3   4.2   &gt;10                  
 
         [0057]    It has also been discovered that point mutations within the HSV-1 polymerase gene that confer resistance to Acyclovir and other nucleoside analogs do not result in resistance to the 4-HQ, 4-oxo-DHQs or 4-oxo-DHTPs. Serial passage of wild type HSV-1 in the presence of 4-oxo-DHQ results in the isolation of mutants that are highly resistant (&gt;20 fold increase in the IC 50 ) to these compounds while retaining sensitivity to nucleoside inhibitors such as Acyclovir.  
         [0058]    In order to determine the mechanism of action of 4-HQ, 4-oxo-DHQ and 4-oxo-DHTP compounds against herpes viruses, mutants resistant to these compounds are isolated by serial passage of the virus in the presence of a 4-oxo-DHQ compound. Sequencing analysis of HSV-1 and HSV-2 strains resistant to the 4-oxo-DHQ identifies that HSV-1 (KOS strain) polymerase protein and its homologous HSV-2 have a conserved region (a binding domain), which is a critical contact point for these compounds. While amino acid numbering of the DNA polymerase may vary between strains of HSV-1 and HSV-2, this binding domain encompassing the HSV-1 (KOS) strain amino acid 823 is highly conserved in herpesviruses and can be identified by alligning the homologous amino acids of this domain as shown in FIG. 2.  
         [0059]    In HSV-1 and HSV-2 strains resistant to the 4-oxo-DHQ and similar compounds, a change of valine to an alanine at the binding domain provides full resistance.  
         [0060]    In the HSV-1 DNA polymerase, resistance is also found when a valine changes to methionine at amino acid 823 but only when accompanied by a second amino acid change.  
         [0061]    Isolation of HCMV resistant to 4-oxo-DHQ&#39;s is found to be very difficult. Comparison of the amino acid sequence of the HSV polymerase (Y-G-F-T-G-V-Q-H-G) and HCMV polymerase (Y-G-F-T-G-V-V-N-G) in the region of amino acid 823 (underlined amino acid) shows that there is a second valine at position 824 in the HCMV polymerase. In vitro assay using mutant HCMV polymerases demonstrates that full resistance to the 4-oxo-DHQs requires changes at both amino acids 823 (a valine to alanine) and 824 (a valine to leucine). A HCMV polymerase gene containing V823A and V824L mutations is used in marker rescue experiments to generate a viral mutant. This mutant has an IC 50  approximately 7-fold above that of wild-type HCMV.  
         [0062]    The HSV-1, HSV-2 and HCMV mutants are also found to be resistant to other non-nucleoside inhibitors such as the 4-oxo-DHTP and similar compounds. However, when the binding domain mutants (e. g. HSV-1 V823A, HSV-2-MS V826A, HSV-2-186 V828A, and HCMV V823A/V824L mutants) are tested in plaque reduction assays against a series of nucleoside polymerase inhibitors and the non-nucleoside inhibitor such as Foscarnet, replication of the mutants is found to be inhibited by all of the currently marketed anti-herpes polymerase inhibitors tested.  
         [0063]    These studies demonstrate that certain non-nucleosides like 4-HQ, 4-oxo-DHQ and 4-oxo-DHTP compounds bind to a different site on the herpes polymerase than the nucleoside inhibitors and Foscarnet. The valine at the binding domain is conserved in the DNA polymerases of six of the eight human herpesviruses and several animal herpesviruses, and appears to play a critical role in the antiviral activity of the 4-HQ, 4-oxo-DHQ and 4-oxo-DHTP compounds. (See FIG. 2)  
         [0064]    Since mutation at the binding domain negates these non-nucleoside inhibitors&#39; activities, compounds could be tested against wild type polymerases and the mutant polymerases to establish the probability of similar binding. We refer to this property of compounds as interaction with the binding domain. Since compounds that interact with the binding domain have exhibited broad-spectrum activity against herpesviruses, this invention provides a method for selecting compounds to treat individuals such as immunocompromised patients who are afflicted with multple herpesvirus infections.  
         [0065]    Definitions  
         [0066]    The term “wild-type” refers to a gene or gene product which has the characteristics of that gene or gene product when isolated from a naturally occurring source. A wild-type gene is that which is most frequently observed in a population and is thus arbitrarily designated the “normal” or “wild-type” form of the gene.  
         [0067]    In contrast, the term “mutant” refers to a gene or gene product which displays modifications in sequence and or functional properties (i.e., altered characteristics) when compared to the wild-type gene or gene product. It is noted that naturally-occurring mutants can be isolated; these are identified by the fact that they have altered characteristics when compared to the wild-type gene or gene product.  
         [0068]    IC 50  refers to concentration of a drug that inhibits virus growth by 50%.  
         [0069]    Wild type HSV-1 and HSV-2 strains are listed in FIG. 4.  
         [0070]    Wild type HCMV is listed in SEQ. ID. NO.13.  
         [0071]    The term “Iudr” refers to antiviral drug Iododeoxyuridine.  
         [0072]    The term “Bvdu” refers to antiviral drug Bromovinyldeoxyuridine.  
         [0073]    The term “ACV” refers to antiviral drug Acyclovir.  
         [0074]    The term “AraC” refers to antiviral drug Arabinosylcytidine.  
         [0075]    The term “AraT” refers to antiviral drug Arabinosylthymine.  
         [0076]    The term “AraA” refers to antiviral drug Arabinosyladenine.  
         [0077]    The term “GCV” refers to antiviral drug Ganciclovir.  
         [0078]    The term “CDV” refers to antiviral drug Cidofovir.  
         [0079]    The term “PFA” refers to antiviral drug Foscarnet.  
         [0080]    The term “binding domain” refers to a conserved region in herpesvirus DNA polymerases. The herpesvirus DNA polymerases have seven (7) conserved regions. The binding domain is within the thrid conserved region (see FIG. 2). When the binding domain contacts with an inhibitor, at least one amino acid in the binding domain mutates and provides the resistance. In general, the binding domain is at an amino acid sequence position 818-829 of the HSV-1 DNA polymerase or the homologous region in other herpes virus DNA polymerases (see FIG. 2).  
         [0081]    The term “a binding domain mutant herpes virus” refers to a herpes virus containing a binding domain mutation.  
         [0082]    More specifically, the binding domain in HSV-1 strains, KOS, F, DJL and Patton are at amino acid sequence position 823. The binding domain in HSV-2 MS-MI strain is at amino acid sequence position 826. The binding domain in HSV-2 186 strain is at amino acid sequence position 828. The binding domain in HCMV AD 169 strains is at amino acid sequence position 823-824.  
         [0083]    The term “XxxxY” refers to an amino acid sequence position xxx, a single amino acid X in wild type is changed to an amino acid Y.  
         [0084]    For example, the term “V823A” refers to an amino acid sequence position 823, a Valine found in wild type is changed to alanine in mutant strain.  
         [0085]    The term “V824L” refers to an amino acid sequence position 824, a Valine found in wild type is changed to Leucine in mutant strain.  
         [0086]    The term “V826A” refers to an amino acid sequence position 826, a Valine found in wild type is change to alanine in mutant strain.  
         [0087]    The term “V828A” refers to an amino acid sequence position 828, a Valine found in wild type is change to alanine in mutant strain.  
         [0088]    A table of amino acids and their representative abbreviations, symbols and codons is set forth below in the following Table.  
                                                                                 Amino acid   Abbrev.   Symbol   Codon(s)                                Alanine   Ala   A   GCA   GCC   GCG   GCU               Cysteine   Cys   C   UGC   UGU       Aspartic acid   Asp   D   GAC   GAU       Glutamic acid   Glu   E   GAA   GAG       Phenylalanine   Phe   F   UUC   UUU       Glycine   Gly   G   GGA   GGC   GGG   GGU       Histidine   His   H   CAC   CAU       Isoleucine   Ile   I   AUA   AUC   AUU       Lysine   Lys   K   AAA   AAG       Leucine   Leu   L   UUA   UUG   CUA   CUC   CUG   CUU       Methionine   Met   M   AUG       Asparagine   Asn   N   AAC   AAU       Proline   Pro   P   CCA   CCC   CCG   CCU       Glutamine   Gln   Q   CAA   CAG       Arginine   Arg   R   AGA   AGG   CGA   CGC   CGG   CGU       Serine   Ser   S   AGC   AGU   UCA   UCC   UCG   UCU       Threonine   Thr   T   ACA   ACC   ACG   ACU       Valine   Val   V   GUA   GUC   GUG   GUU       Tryptophan   Trp   W   UGG       Tyrosine   Tyr   Y   UAC   UAU                  
 
       Material and Methods  
       [0089]    Cell and Viruses  
         [0090]    African green monkey kidney cells (Vero) and human foreskin fibroblast cells (HFF) and herpes viruses can be obtained from the American Type Culture Collection (ATCC). Media is defined as Dulbecco&#39;s modified Eagle media (DMEM) containing 10% fetal bovine serum (FBS) and supplemented with antibiotics. Cells are maintained in media at 37° C. in a humidified atmosphere of 5% CO 2 . HSV-1 strains F, Patton and DJL, HSV-2 strains MS, 35D and 186, and HCMV strain AD 169 are used in these studies. Strain DJL is a clinical isolate of HSV-1 isolated in our lab from a primary oral lesion.  
         [0091]    Measuring IC 50  of a Compound of Interest That Inhibits Herpes Viruses  
         [0092]    Preparation of Virus Stocks  
         [0093]    HSV-1 and HSV-2 stocks are grown in Vero cells. HCMV stocks are grown in HFF cells. Approximately 1 ml of media containing sufficient virus to infect approximately 0.1% to 1% of the cells (multiplicity of infection of 0.001 to 0.01 PFU/cell) is added to a T-150 cell culture flask containing a confluent monolayer of cells. The cells are incubated at 37° C. for approximately I hour. Approximately 50 ml of media is then added to the flask and the cells are incubated at 37° C. until viral cytopathic effect (cpe) is apparent in 100% of the cells. The flask is then placed at −80° C. for at least 30 min. The flask containing frozen media and cells is placed in a 37° C. water bath until the media is thawed. This process disrupts the cells and releases virus into the media. 1 ml aliquots of media containing virus are dispensed into tubes and stored at −80° C. These aliquots of media containing virus are referred to as virus stocks.  
         [0094]    Titrating Virus Stocks  
         [0095]    Aliquots of virus are thawed at 37° C. and serially diluted (10 fold dilutions) in media. 0.1 ml of each dilution of virus is placed in a single well of 24-well cell culture dish containing a confluent monolayer of cells (Vero cells for HSV-1 and HSV-2, HFF cells for HCMV) and incubated at 37° C. for 1 h. The virus innoculum is then removed and 1 ml of media containing 0.8% carboxymethylcellulose (CMC) is added to each well of the dish. The dish is incubated at 37° C. for approximately 2-3 days (HSV-1 and HSV-2) or 6-9 days (HCMV) to allow sufficient growth of virus to form plaques in the cell monolayer. Plaques can be observed and counted microscopically or by staining the cells with 0.1% crystal violet in 20% ethanol. The virus titer which is expressed as plaque forming units (PFU) per ml is obtained by counting the plaques in a well and correcting for the dilution of the viral innoculum.  
         [0096]    Plaque Reduction Assays  
         [0097]    Antiviral activity of compounds against herpesviruses such as HSV-1, HSV-2, or HCMV can be measured using plaque reduction assays. 0.1 ml of media containing approximately 50 PFU of virus is added to each well of a 24-well cell culture dish containing a confluent monolayer of cells (Vero cells for HSV-1 and HSV-2, HFF cells for HCMV). Compounds are dissolved in 100% DMSO and diluted in 100% DMSO as 200× stocks of the desired final drug concentration. Typically 5-6 two-fold dilutions are prepared for each compound. Dilutions of compounds are then added to media containing 0.8% CMC resulting in a final 1× drug concentration. After the virus-infected cells have incubated for 1 h at 37° C., the virus innoculum is removed and 1 ml of media containing 0.8% CMC and the various concentrations of compound is added to each well of the dish. The dish is incubated at 37° C. for approximately 2-3 days (HSV-1 and HSV-2) or 6-9 days (HCMV) to allow sufficient growth of virus to form plaques in the cell monolayer. Plaques can be observed and counted microscopically or by staining the cells with 0.1% crystal violet in 20% ethanol. Virus inhibition is determined for each drug concentration by comparing the number of plaques in drug-containing wells to control wells that did not contain drug. Antiviral activity of a compound is expressed as the concentration of compound predicted to reduce the number of plaques in a well by 50% (IC 50 ). The IC 50  values are calculated by plotting the per cent inhibition vs. concentration of compound using EXCEL software for linear regression.  
         [0098]    Selection of 4-oxo-DHQ Resistant HSV-1 and HSV-2  
         [0099]    Vero cells are plated out at a density of 3.5×10 5  cells per well in a six well tissue culture plate. Cells are infected with HSV-1 KOS at a multiplicity of infection (moi) of 0.1 pfu/cell and 1 h post infection the cells are overlayed with 3 ml media containing 20 uM of a 4-oxo-DHQ. Cultures are incubated for 20 h at 37° C., freeze/thawed to release cell-associated virus, and 0.1 ml of culture is used to infect a new monolayer of Vero cells (one passage). Serial passage is repeated seven times in the presence of 20 uM drug. Virus isolates are then plaque purified three times prior to preparation of stocks. Virus recovered from each passage in the presence of compound No. 17 is shown in FIG. 3. 4-oxo-DHQ resistant HSV-1 and HSV-2 may also be selected by the marker transfer method described below using wild-type HSV DNA and the corresponding mutant HSV polymerase gene.  
         [0100]    Marker Transfer of a HCMV Mutation  
         [0101]    A plasmid containing the wild-type HCMV polymerase gene is modified to contain the V823A or V823A and V824L mutations using a site-directed mutagenesis Kit (Stratagene Corp.) and following the manufactures&#39;s protocol. HFF cells are plated into T25 tissue culture flasks to achieve 80% confluency at the time of the transfection. Wild type HCMV AD 169 DNA and plasmid DNA containing the mutant HCMV polymerase gene are mixed at a ratio of 1:2 (2ug of viral DNA to 4 ug of plasmid DNA). DNA&#39;s are transfected using superfect transfection reagent according to methods recommended by the manufacturer (Quiagen Inc.). Cells are harvested five days posttransfection, freeze-thawed to release virus and half of the sample is used to infect HFF cell monolayers. Cells are overlayed with media containing 20 uM 4-oxo-DHQ compound 2 (see FIG. 1). Serial passage is repeated seven times in the presence of 20 uM compound 2 and virus isolates are then plaque purified three times prior to preparation of viral stock.  
         [0102]    Isolation of HSV and HCMV Viral DNA  
         [0103]    HSV DNA is purified from the cytoplasm of infected Vero cells. Vero cells (50% confluent) are infected at an multiplicity of 0.01 PFU/cell. At 3-5 days postinfection infected cells (100% cpe) are harvested by centrifugation at 1000 rpm in a Beckman GS-6R centrifuge. The pelleted cells are resuspended in TE buffer and placed on ice for 15 minutes. NP-40 is then added to a final concentration of 0.2% and incubated on ice for a further 15 minutes. The cells are centrifuged at 2000 rpm for 10 minutes in a Beckman GS-6R centrifuge. The supernatant is removed and EDTA is added to a final concentration of 20 mM followed by the addition of SDS to a final concentration of 0.3% and proteinase K to a concentration of 50 ug/ml then incubated at 45 C. for 2 hours. HCMV DNA is isolated by infecting HFF cells (25% confluency) with HCMV at an multiplicity of 0.1 PFU/cell. Cells and media are harvested 5-7 days postinfection (100% cpe) and subjected to low speed centrifugation to remove intact cells and cell debris followed by a high speed spin to pellet virus particles (2500 rpm&#39;s in a Beckman SW28 rotor for 1 hour). Following incubation of the HSV and HCMV samples, 1.5 volumes of saturated NaI is added to the digested extract and the refractive index is adjusted to 1.434-1.435. Ethidium bromide is added to a final concentration of 50 ug/ml. The samples are loaded into a VTI 50 centrifuge tube and spun for 24 hours at 45,000 rpm. The DNA band is harvested extracted three times with n-butanol, then dialyzed against TE buffer followed by a dialysis against 95% ethanol and a final dialysis against TE buffer.  
         [0104]    DNA Sequencing  
         [0105]    HSV-1, HSV-2 or HCMV viral DNA&#39;s are sequenced directly using an ABI377 fluorescence sequencer (Perkin Elmer Applied Biosystems, Foster City, Calif.) and the ABI BigDye PRISMTM dRhodamine Terminator Cycle Sequencing Ready Reaction Kit with AmpliTaq FSTM DNA polymerase (PE Applied Biosystems). Each cycle sequencing reaction contained about 1.0 ug of purified viral DNA. Cycle-sequencing is performed using an initial denaturation at 98° C. for 1 min, followed by 50 cycles: 98° C. for 30 sec, annealing at 50° C. for 30 sec, and extension at 60° C. for 4 min. Temperature cycles and times are controlled by a Perkin-Elmer 9700 thermocycler. Extension products are purified using CentriflexTM gel filtration cartridges (Edge BioSystems, Gaithersburg, Md.). Each reaction product is loaded by pipette onto the column, which is then centrifuged in a swinging bucket centrifuge (Sorvall model RT6000B table top centrifuge) at 750×g for 1.5 min at room temperature. Column-purified samples are dried under vacuum for about 40 min and then dissolved in 4 ul of a DNA loading solution (83% deionized formamide, 8.3 mM EDTA, and 1.6 mg/ml Blue Dextran). The samples are then heated to 90° C. for two min, and held at 4° C. until loading. 1.5 ul of each sample is loaded into a single well of the ABI377 sequencer. Sequence chromatogram data files from the ABI377 are analyzed with the computer program Sequencher (Gene Codes, Ann Arbor, Md., for assembly of sequence fragments and correction of ambiguous base calls. Generally sequence reads of 600-700 bp are obtained. Potential sequencing errors are minimized by obtaining sequence information from both DNA strands and by re-sequencing difficult areas using primers at different locations until all sequencing ambiguities are removed.  
         [0106]    The entire coding region of the polymerase genes from both the parent strains and the resistant viruses are sequenced. The DNA sequencing is done using viral DNA as the template thus avoiding cloning of the polymerase genes. The amino acid sequence of the DNA polymerases of HSV-1 KOS, F, Patton and DJL and HSV-2 MS and 186 are compared in FIG. 4. Amino acids that are identical for the six polymerases are shaded in black while regions where amino acid differences are found are shaded in gray. The amino acid sequence of the four HSV-1 polymerases are essentially identical with only a few minor changes noted between the different HSV-1 strains. The majority of amino acid changes are found when the sequences of the HSV-1 and HSV-2 polymerases are compared.  
         [0107]    Isolation and Characterization of HSV-1 and HSV-2 Mutants That Are Resistant To the 4-oxo-DHQ&#39;s and 4-oxo-DHTP Compounds  
         [0108]    A panel of viruses consisting of four strains of HSV-1 (KOS, F, DJL, Patton) and three strains of HSV-2 (MS, 35D, 186) are tested in a plaque reduction assay against four different 4-oxo-DHQ compounds (#1, 2, 4, 5 as shown in FIG. 1), and one 4-oxo-DHTP compound (#3 as shown in FIG. 1) and against Acyclovir. The six drugs inhibited replication of the seven virus strains with IC 50  values ranging from 2-10 μM (Table 1). In order to select for 4-oxo-DHQ resistant mutants, HSV-1 strains KOS, F, and DJL along with HSV-2 strains 186 and MS are serially passaged in the presence of 20 uM compound 1. Following the seventh passage, 4-oxo-DHQ resistant virus from each strain are plaque purified three times and high-titer stocks are made. All of the resistant HSV mutants grew to high titers in Vero cells, indicating that the mutations in the resistant isolates did not significantly impair their growth. The mutants selected with 4-oxo-DHQ compound 1 exhibited &gt;10 fold increase in IC 50  when tested in a plaque reduction assay against 4-oxo-DHQ compound 1 Data are shown in Table 2.  
                             TABLE 2                           4-oxo-DHQ Resistant Virus of HSV-1 and HSV-2                Compound 1   Amino Acid Change in HSV       Virus Mutants   IC 50  (uM)   DNA Polymerase               HSV-1 Kos-M1   &gt;20   −V823A       HSV-1 F-M1   &gt;20   −V823A       HSV-1 DJL-M1   &gt;20   −V823A       HSV-2 MS-M1   &gt;20   −V826A       HSV-2 186-M1   &gt;20   −V828A                          
 
         [0109]    DNA sequence analysis of the 4-oxo-DHQ resistant mutants (HSV-1 KOS-M1, HSV-1 F-M1, HSV-1 DJL-M1, HSV-2 186-MI, HSV-2 MS-M1) demonstrated that all five mutants contained a single point mutation of T to C at the binding domain resulting in a Valine to Alanine amino acid change.  
         [0110]    Isolation and Characterization of a HCMV Mutant that is Resistant to The 4-oxo-DHQ&#39;s and 4-oxo-DHTP Compounds  
         [0111]    In order to select for a 4-oxo-DHQ HCMV resistant mutant, virus (strain AD169) is serially passaged in the presence of 20 uM a 4-oxo-DHQ. Although we could readily select for HSV mutants using this procedure we failed to isolate an HCMV mutant, even when the virus is passaged at low drug concentrations (&lt;5 uM). Comparison of the amino acid sequence of the HSV polymerase, Y-G-F-T-G-V-Q-H-G, and HCMV polymerase, Y-G-F-T-G-V-V-N-G, in the region of amino acid 823 (underlined amino acid) showed that there is a second valine at position 824 in the HCMV polymerase. In order to determine if both valines need to be changed in order to confer resistance to the 4-oxo-DHQ&#39;s, in vitro polymerase assays are done using mutant HCMV polymerases containing either V823A or V823A plus V824L (Table 3).  
                                           TABLE 3                           HCMV Mutant Polymerase Exhibits Resistance to 4-oxo-DHQ*                Polymerase   Compound 1 IC 50  (uM)                            HCMV (wild)   4.6           HCMV V823A   17.2           HCMV V823A/V824L   42.9                                              
 
         [0112]    The V823A alone resulted in a 3.5-fold increase in the IC 50  while the polymerase with the double amino acid change had nearly 10-fold increase in the IC 50 . In order to isolate an HCMV resistant mutant marker rescue experiments are done. Plasmids containing the mutant polymerase genes are transfected into HFF cells along with wild type HCMV AD169 DNA. The resulting virus is then serially passaged in the presence of 20 uM compound 1 (see FIG. 1). A 4-oxo-DHQ resistant virus is isolated from marker rescue studies done with the HCMV polymerase gene containing mutations that result in the V823A, V824L amino acid changes, but not with the gene containing V823A change alone. The mutant selected with compound 1 (HCMV AD169-M1) exhibited ˜7-fold increase in IC 50  when tested in a plaque reduction assay compared to Ganciclovir and cidofovir which has a &lt;2-fold change in sensitivity (Table 4).  
                             TABLE 4                           Plaque reduction assay of 4-oxo-DHQ resistant HCMV*                HCMV AD169   HCMV AD169 - M1       Drug   IC 50  (μM)   IC 50  (μM)               Compound 1   0.7   4.7       Ganciclovir   0.9   1.0       Cidofovir   0.3   0.6                                  
 
         [0113]    The entire coding region of the HCMV polymerase genes from both the parent strain and the resistant virus are sequenced. The DNA sequencing is again done using viral DNA as the template thus avoiding cloning of the polymerase genes. Comparison of the DNA sequence of the two polymerase genes demonstrated that the resistant mutant contained two point mutations that resulted in the predicted V823A, V824L amino acid changes. As with the HSV resistant viruses these results demonstrate the critical role of the region encompassing amino acid 823 for inhibition of polymerase activity by these compounds.  
         [0114]    Antiviral Activity of Nucleoside and Non-Nucleoside Polymerase Inhibitors Against 4-oxo-DHQ Resistant Mutants  
         [0115]    In order to determine if the 4-HQ binding domain mutations alter the sensitivity of the HSV-1, HSV-2 and HCMV mutants to both non-nucleoside (4-oxo-DHQ&#39;s) and nucleoside inhibitors (e.g Acyclovir and ganciclovir) several of the mutants are tested in plaque reduction assays against a series of non-nucleoside compounds including Foscarnet (PFA), 4-HQ&#39;s 4-oxo-DHQ&#39;s and 4-oxo-DHTP&#39;s (Table 5). The mutants are also tested against a series of nucleoside inhibitors including acyclovir and ganciclovir (Table 5). The activity of these compounds against the mutants is compared to their activity against the wild type strains that are used to isolate the HSV and HCMV mutants. When tested against a number of 4-HQ&#39;s, 4-oxo-DHQ&#39;s and 4-oxo-DHTP&#39;s and other related classes of compounds all of the drugs are found to inhibit the wild type virus with IC 50  values ranging from &lt;0.1 uM to 30 uM. When these drugs are tested against the resistant viruses they are found to have IC 50  values 5 to 10 fold higher then the parent virus. There is little if any difference in the IC 50  values of the nucleoside compounds and the non-nucleoside PFA between the wild type and mutant HSV-1, HSV-2, and HCMV viruses. These results demonstrate that the amino acid change in the binding domain (V823A in the HSV-1 polymerase, V826A in the HSV2-MS polymerase, V828A in the HSV2-186 polymerase, and the V823A/V824L changes in the HCMV polymerase) resulted in resistance to the 4-oxo-DHQ&#39;s and 4-oxo-DHTP&#39;s, which provides further evidence that these classes of compounds share an affinity for a region we refer to as the binding domain. In contrast, these amino acid changes did not alter the activity of these viruses to other classes of polymerase inhibitors.  
                                                                                     TABLE 5                           Antiviral activity of nucleoside and non-nucleoside polymerase inhibitors       against HSV-1, HSV-2, and HCMV Isolates selected for       4-oxo-DHQ resistance*                Plaque Reduction Assay - IC 50  (μM)                HSV-2   HSV-2   HSV-1   HSV-1   HCMV   HCMV       Drug   MS   MS-M1   KOS   KOS-M1   AD169   AD169-M1                    6   28.8   &gt;50   24.6   &gt;50   5.1   &gt;16       7   8.8   27.9   6.5   &gt;50   0.3   3.4       8   2.3   &gt;50   5.1   &gt;50   &lt;0.1   1.1       9   0.9   48.7   1.9   &gt;50   &lt;0.1   3.1       10   29.2   &gt;50   15.8   &gt;50   1.1   &gt;16       11   3.0   &gt;50   3.1   &gt;50   0.7   3.9       12   0.4   12.5   1.3   &gt;50   0.2   1.1       13   5.3   &gt;50   5.5   &lt;25   2.7   &gt;16       14   1.6   &gt;50   28.4   &gt;50   0.9   18.4       2   1.3   &gt;50   3.3   &gt;50   0.4   4.0       4   2.1   28.4   4.2   &gt;50   0.6   2.1       3   0.8   &gt;50   4.0   &gt;50   1.5   6.2       15   5.9   &gt;50   &gt;50   &gt;50   0.7   7.7       Iudr   5.0   6.1   1.1   0.8   ND   ND       Bvdu   5.8   5.9   2.1   0.1   ND   ND       ACV   2.4   2.8   3.9   4.4   ND   ND       AraC   0.2   0.1   0.2   0.2   ND   ND       AraT   6.6   3.6   11.6   3.6   ND   ND       AraA   10.6   18.2   26.1   27.2   ND   ND       GCVir   ND   ND   ND   ND   0.8   0.8       CDV   ND   ND   ND   ND   0.4   0.3       PFA   ND   ND   ND   ND   38   &lt;20                                          
 
         [0116]    Antiviral compounds identified by the present invention can conveniently be administered in a pharmaceutical composition containing the compound in combination with a suitable excipient, the composition being useful in combating viral infections. Pharmaceutical compositions containing a compound appropriate for antiviral use are prepared by methods and contain excipients which are well known in the art. A generally recognized compendium of such methods and ingredients is Remington&#39;s Pharmaceutical Science by E. W. Martin (Mark Publ. Co., 15th Ed., 1975).  
         [0117]    Antiviral compounds identified by the present invention and their compositions can be administered parenterally (for example, by intravenous, intraperitoneal or intramuscular injection), topically, orally, or rectally, depending on whether the preparation is used to treat internal or external viral infections.  
         [0118]    For oral therapeutic administration, the active compound may be combined with one or more excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. Such compositions and preparations should contain at least 0.1% of active compound. The percentage of the compositions and preparations may, of course, be varied and may conveniently be between about 2 to about 60% of the weight of a given unit dosage form. The amount of active compound in such therapeutically useful compositions is such that an effective dosage level will be obtained.  
         [0119]    The tablets, troches, pills, capsules, and the like may also contain the following: binders such as gum tragacanth, acacia, corn starch or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, fructose, lactose or aspartame or a flavoring agent such as peppermint, oil of wintergreen, or cherry flavoring may be added. When the unit dosage form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier, such as a vegetable oil or a polyethylene glycol. Various other materials may be present as coatings or to otherwise modify the physical form of the solid unit dosage form. For instance, tablets, pills, or capsules may be coated with gelatin, wax, shellac or sugar and the like. A syrup or elixir may contain the active compound, sucrose or fructose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavoring such as cherry or orange flavor. Of course, any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed. In addition, the active compound may be incorporated into sustained-release preparations and devices.  
         [0120]    Antiviral compounds identified by the present invention and their compositions can also be administered intravenously or intraperitoneally by infusion or injection. Solutions of the active compound or its salts can be prepared in water, optionally mixed with a nontoxic surfactant. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, triacetin, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.  
         [0121]    Pharmaceutical dosage forms suitable for injection or infusion can include sterile aqueous solutions or dispersions or sterile powders comprising the active ingredient which are adapted for the extemporaneous preparation of sterile injectable or infusible solutions or dispersions, optionally encapsulated in liposomes. In all cases, the ultimate dosage form should be sterile, fluid and stable under the conditions of manufacture and storage. The liquid carrier or vehicle can be a solvent or liquid dispersion medium comprising, for example, water, ethanol, a polyol (for example, glycerol, propylene glycol, liquid polyethylene glycols, and the like), vegetable oils, nontoxic glyceryl esters, and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the formation of liposomes, by the maintenance of the required particle size in the case of dispersions or by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, buffers or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin.  
         [0122]    Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filter sterilization. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and the freeze drying techniques, which yield a powder of the active ingredient plus any additional desired ingredient present in the previously sterile-filtered solutions.  
         [0123]    For topical administration, the present compounds may be applied in pure form, i.e., when they are liquids. However, it will generally be desirable to administer them to the skin as compositions or formulations, in combination with a dermatologically acceptable carrier, which may be a solid or a liquid.  
         [0124]    Useful solid carriers include finely divided solids such as talc, clay, microcrystalline cellulose, silica, alumina and the like. Useful liquid carriers include water, alcohols or glycols or water-alcohol/glycol blends, in which the present compounds can be dissolved or dispersed at effective levels, optionally with the aid of non-toxic surfactants. Adjuvants such as fragrances and additional antimicrobial agents can be added to optimize the properties for a given use. The resultant liquid compositions can be applied from absorbent pads, used to impregnate bandages and other dressings, or sprayed onto the affected area using pump-type or aerosol sprayers. Thickeners such as synthetic polymers, fatty acids, fatty acid salts and esters, fatty alcohols, modified celluloses or modified mineral materials can also be employed with liquid carriers to form spreadable pastes, gels, ointments, soaps, and the like, for application directly to the skin of the user.  
         [0125]    Examples of useful dermatological compositions which can be used to deliver the compounds of formula I to the skin are known to the art; for example, see Jacquet et al. (U.S. Pat. No. 4,608,392), Geria (U.S. Pat. No. 4,992,478), Smith et al. (U.S. Pat. No. 4,559,157) and Wortzman (U.S. Pat. No. 4,820,508).  
         [0126]    Useful dosages of the compounds of formula I can be determined by comparing their in vitro activity, and in vivo activity in animal models. Methods for the extrapolation of effective dosages in mice, and other animals, to humans are known to the art; for example, see U.S. Pat. No. 4,938,949.  
         [0127]    The compound is conveniently administered in unit dosage form; for example, containing 5 to 1000 mg, conveniently 10 to 750 mg, most conveniently, 50 to 500 mg of active ingredient per unit dosage form. The desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals, for example, as two, three, four or more sub-doses per day. The sub-dose itself may be further divided, e.g., into a number of discrete loosely spaced administrations; such as multiple inhalations from an insufflator or by application of a plurality of drops into the eye.  
         [0128]    For internal infections, the compositions can be administered orally or parenterally at dose levels, calculated as the free base, of about 0.1 to 300 mg/kg, preferably 1.0 to 30 mg/kg of mammal body weight, and can be used in man in a unit dosage form, administered one to four times daily in the amount of 1 to 1000 mg per unit dose.  
         [0129]    For parenteral administration or for administration as drops, as for eye infections, the compounds are presented in aqueous solution in a concentration of from about 0.1 to about 10%, more preferably about 0.1 to about 7%. The solution may contain other ingredients, such as emulsifiers, antioxidants or buffers.  
         [0130]    Generally, the concentration of the compound(s) of formula I in a liquid composition, such as a lotion, will be from about 0.1-25 wt-%, preferably from about 0.5-10 wt-%. The concentration in a semi-solid or solid composition such as a gel or a powder will be about 0.1-5 wt-%, preferably about 0.5-2.5 wt-%.  
         [0131]    The exact regimen for administration of the compounds and compositions disclosed herein will necessarily be dependent upon the needs of the individual subject being treated, the type of treatment and, of course, the judgment of the attending practitioner.  
         [0132]    The antiviral activity of a compound of the invention can be determined using pharmacological models which are well known to the art, or using Test A described below.  
         [0133]    The compounds of formula (I) and pharmaceutically acceptable salts thereof are useful as antiviral agents. Thus, they are useful to combat viral infections in animals, including man. The compounds are generally active against herpes viruses, and are particularly useful against the varicella zoster virus, the Epstein-Barr virus, the herpes simplex virus, the human herpes virus type 8 (HHV-8) and the cytomegalovirus (CMV).  
     
       
       
         1 
         
           
             19  
           
           
             1  
             3717  
             DNA  
             herpes simplex  
           
            1 

atgttttgtg ccgcgggcgg cccgacttcc cccgggggga agtcggcggc tcgggcggcg     60 

tctgggtttt ttgcccccca caacccccgg ggagccaccc agacggcacc gccgccttgc    120 

cgccggcaga acttctacaa cccccacctc gctcagaccg gaacgcagcc aaaggccccc    180 

gggccggctc agcgccatac gtactacagc gagtgcgacg aatttcgatt tatcgccccg    240 

cgttcgctgg acgaggacgc ccccgcggag cagcgcaccg gggtccacga cggccgcctc    300 

cggcgcgccc ctaaggtgta ctgcgggggg gacgagcgcg acgtcctccg cgtgggcccg    360 

gagggcttct ggccgcgtcg cttgcgcctg tggggcggtg cggaccatgc ccccaagggg    420 

ttcgacccca ccgtcaccgt cttccacgtg tacgacatcc tggagcacgt ggaacacgcg    480 

tacagcatgc gcgccgccca gctccacgag cgatttatgg acgccatcac gcccgccggg    540 

accgtcatca cgcttctggg tctgaccccc gaaggccatc gcgtcgccgt tcacgtctac    600 

ggcacgcggc agtactttta catgaacaag gcggaggtgg atcggcacct gcagtgccgt    660 

gccccgcgcg atctctgcga gcgcctggcg gcggccctgc gcgagtcgcc gggggcgtcg    720 

ttccgcggca tctccgcgga ccacttcgag gcggaggtgg tggagcgcgc cgacgtgtac    780 

tattacgaaa cgcgcccgac cctgtactac cgcgtcttcg tgcgaagcgg gcgcgcgctg    840 

gcctacctgt gcgacaactt ttgccccgcg atcaggaagt acgagggggg cgtcgacgcc    900 

accacccggt ttatcctgga caacccgggg tttgtcacct tcggctggta ccgcctcaag    960 

cccggccgcg ggaacgcgcc ggcccaaccg cgccccccga cggcgttcgg aacctcgagc   1020 

gacgtcgagt ttaactgcac ggcggacaac ctggccgtcg agggggccat gtgtgacctg   1080 

ccggcctaca agctcatgtg cttcgatatc gaatgcaagg ccggggggga ggacgagctg   1140 

gcctttccgg tcgcggaacg cccggaagac ctcgtcatcc agatctcctg tctgctctac   1200 

gacctgtcca ccaccgccct cgagcacatc ctcctgtttt cgctcggatc ctgcgacctc   1260 

cccgagtccc acctcagcga tctcgcctcc aggggcctgc cggcccccgt cgtcctggag   1320 

tttgacagcg aattcgagat gctgctggcc ttcatgacct tcgtcaagca gtacggcccc   1380 

gagttcgtga ccgggtacaa catcatcaac ttcgactggc ccttcgtcct gaccaagctg   1440 

acggagatct acaaggtccc gctcgacggg tacgggcgca tgaacggccg gggtgtgttc   1500 

cgcgtgtggg acatcggcca gagccacttt cagaagcgca gcaagatcaa ggtgaacggg   1560 

atggtgaaca tcgacatgta cggcatcatc accgacaagg tcaaactctc cagctacaag   1620 

ctgaacgccg tcgccgaggc cgtcttgaag gacaagaaga aggatctgag ctaccgcgac   1680 

atccccgcct actacgcctc cgggcccgcg cagcgcgggg tgatcggcga gtattgtgtg   1740 

caggactcgc tgctggtcgg gcagctgttc ttcaagtttc tgccgcacct ggagctttcc   1800 

gccgtcgcgc gcctggcggg catcaacatc acccgcacca tctacgacgg ccagcagatc   1860 

cgcgtcttca cgtgcctcct gcgccttgcg ggccagaagg gcttcatcct gccggacacc   1920 

caggggcggt ttcggggcct cgacaaggag gcgcccaagc gcccggccgt gcctcggggg   1980 

gaaggggagc ggccggggga cgggaacggg gacgaggata aggacgacga cgaggacgag   2040 

gacggggacg agcgcgagga ggtcgcgcgc gagaccgggg gccggcacgt tgggtaccag   2100 

ggggcccggg tcctcgaccc cacctccggg tttcacgtcg accccgtggt ggtgtttgac   2160 

tttgccagcc tgtaccccag catcatccag gcccacaacc tgtgcttcag tacgctctcc   2220 

ctgcggcccg aggccgtcgc gcacctggag gcggaccggg actacctgga gatcgaggtg   2280 

gggggccgac ggctgttctt cgtgaaggcc cacgtacgcg agagcctgct gagcatcctg   2340 

ctgcgcgact ggctggccat gcgaaagcag atccgctcgc ggatccccca gagcaccccc   2400 

gaggaggccg tcctcctcga caagcaacag gccgccatca aggtggtgtg caactcggtg   2460 

tacgggttca ccggggcgca gcacggtctt ctgccctgcc tgcacgtggc cgccaccgtg   2520 

acgaccatcg gccgcgagat gctcctcgcg acgcgcgcgt acgtgcacgc gcgctgggcg   2580 

gagttcgatc agctgctggc cgactttccg gaggcggccg gcatgcgcgc ccccggtccg   2640 

tactccatgc gcatcatcta cggggacacg gactccattt tcgttttgtg ccgcggcctc   2700 

acggccgcgg gcctggtggc catgggcgac aagatggcga gccacatctc gcgcgcgctg   2760 

ttcctccccc cgatcaagct cgagtgcgaa aaaacgttca ccaagctgct gctcatcgcc   2820 

aagaaaaagt acatcggcgt catctgcggg ggcaagatgc tcatcaaggg cgtggatctg   2880 

gtgcgcaaaa acaactgcgc gtttatcaac cgcacctcca gggccctggt cgacctgctg   2940 

ttttacgacg ataccgtatc cggagcggcc gccgcgttag ccgagcgccc cgcagaggag   3000 

tggctggcgc gacccctgcc cgagggactg caggcgttcg gggccgtcct cgtagacgcc   3060 

catcggcgca tcaccgaccc ggagagggac atccaggact ttgtcctcac cgccgaactg   3120 

agcagacacc cgcgcgcgta caccaacaag cgcctggccc acctgacggt gtattacaag   3180 

ctcatggccc gccgcgcgca ggtcccgtcc atcaaggacc ggatcccgta cgtgatcgtg   3240 

gcccagaccc gcgaggtaga ggagacggtc gcgcggctgg ccgccctccg cgagctagac   3300 

gccgccgccc caggggacga gcccgccccc ccagcggccc tgccctcccc ggccaagcgc   3360 

ccccgggaga cgccgtcgca tgccgacccc ccgggaggcg cgtccaagcc ccgcaagctg   3420 

ctggtgtccg agctggcgga ggatcccggg tacgccatcg cccggggcgt tccgctcaac   3480 

acggactatt acttctcgca cctgctgggg gcggcctgcg tgacgttcaa ggccctgttt   3540 

ggaaataacg ccaagatcac cgagagtctg ttaaagaggt ttattcccga gacgtggcac   3600 

cccccggacg acgtggccgc gcggctcagg gccgcggggt tcgggccggc gggggccggc   3660 

gctacggcgg aggaaactcg tcgaatgttg catagagcct ttgatactct agcatga      3717 

 
           
             2  
             1238  
             PRT  
             herpes simplex  
           
            2 

Met Phe Cys Ala Ala Gly Gly Pro Thr Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro His Asn Pro Arg Gly Ala 
            20                  25                  30 

Thr Gln Thr Ala Pro Pro Pro Cys Arg Arg Gln Asn Phe Tyr Asn Pro 
        35                  40                  45 

His Leu Ala Gln Thr Gly Thr Gln Pro Lys Ala Pro Gly Pro Ala Gln 
    50                  55                  60 

Arg His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro 
65                  70                  75                  80 

Arg Ser Leu Asp Glu Asp Ala Pro Ala Glu Gln Arg Thr Gly Val His 
                85                  90                  95 

Asp Gly Arg Leu Arg Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu 
            100                 105                 110 

Arg Asp Val Leu Arg Val Gly Pro Glu Gly Phe Trp Pro Arg Arg Leu 
        115                 120                 125 

Arg Leu Trp Gly Gly Ala Asp His Ala Pro Lys Gly Phe Asp Pro Thr 
    130                 135                 140 

Val Thr Val Phe His Val Tyr Asp Ile Leu Glu His Val Glu His Ala 
145                 150                 155                 160 

Tyr Ser Met Arg Ala Ala Gln Leu His Glu Arg Phe Met Asp Ala Ile 
                165                 170                 175 

Thr Pro Ala Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly 
            180                 185                 190 

His Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met 
        195                 200                 205 

Asn Lys Ala Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp 
    210                 215                 220 

Leu Cys Glu Arg Leu Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser 
225                 230                 235                 240 

Phe Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg 
                245                 250                 255 

Ala Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Thr Leu Tyr Tyr Arg Val 
            260                 265                 270 

Phe Val Arg Ser Gly Arg Ala Leu Ala Tyr Leu Cys Asp Asn Phe Cys 
        275                 280                 285 

Pro Ala Ile Arg Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe 
    290                 295                 300 

Ile Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys 
305                 310                 315                 320 

Pro Gly Arg Gly Asn Ala Pro Ala Gln Pro Arg Pro Pro Thr Ala Phe 
                325                 330                 335 

Gly Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala 
            340                 345                 350 

Val Glu Gly Ala Met Cys Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe 
        355                 360                 365 

Asp Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val 
    370                 375                 380 

Ala Glu Arg Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr 
385                 390                 395                 400 

Asp Leu Ser Thr Thr Ala Leu Glu His Ile Leu Leu Phe Ser Leu Gly 
                405                 410                 415 

Ser Cys Asp Leu Pro Glu Ser His Leu Ser Asp Leu Ala Ser Arg Gly 
            420                 425                 430 

Leu Pro Ala Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu 
        435                 440                 445 

Leu Ala Phe Met Thr Phe Val Lys Gln Tyr Gly Pro Glu Phe Val Thr 
    450                 455                 460 

Gly Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Val Leu Thr Lys Leu 
465                 470                 475                 480 

Thr Glu Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly 
                485                 490                 495 

Arg Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys 
            500                 505                 510 

Arg Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly 
        515                 520                 525 

Ile Ile Thr Asp Lys Val Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val 
    530                 535                 540 

Ala Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp 
545                 550                 555                 560 

Ile Pro Ala Tyr Tyr Ala Ser Gly Pro Ala Gln Arg Gly Val Ile Gly 
                565                 570                 575 

Glu Tyr Cys Val Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys 
            580                 585                 590 

Phe Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile 
        595                 600                 605 

Asn Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr 
    610                 615                 620 

Cys Leu Leu Arg Leu Ala Gly Gln Lys Gly Phe Ile Leu Pro Asp Thr 
625                 630                 635                 640 

Gln Gly Arg Phe Arg Gly Leu Asp Lys Glu Ala Pro Lys Arg Pro Ala 
                645                 650                 655 

Val Pro Arg Gly Glu Gly Glu Arg Pro Gly Asp Gly Asn Gly Asp Glu 
            660                 665                 670 

Asp Lys Asp Asp Asp Glu Asp Glu Asp Gly Asp Glu Arg Glu Glu Val 
        675                 680                 685 

Ala Arg Glu Thr Gly Gly Arg His Val Gly Tyr Gln Gly Ala Arg Val 
    690                 695                 700 

Leu Asp Pro Thr Ser Gly Phe His Val Asp Pro Val Val Val Phe Asp 
705                 710                 715                 720 

Phe Ala Ser Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu Cys Phe 
                725                 730                 735 

Ser Thr Leu Ser Leu Arg Pro Glu Ala Val Ala His Leu Glu Ala Asp 
            740                 745                 750 

Arg Asp Tyr Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe Phe Val 
        755                 760                 765 

Lys Ala His Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg Asp Trp 
    770                 775                 780 

Leu Ala Met Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser Thr Pro 
785                 790                 795                 800 

Glu Glu Ala Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys Val Val 
                805                 810                 815 

Cys Asn Ser Val Tyr Gly Phe Thr Gly Ala Gln His Gly Leu Leu Pro 
            820                 825                 830 

Cys Leu His Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu Met Leu 
        835                 840                 845 

Leu Ala Thr Arg Ala Tyr Val His Ala Arg Trp Ala Glu Phe Asp Gln 
    850                 855                 860 

Leu Leu Ala Asp Phe Pro Glu Ala Ala Gly Met Arg Ala Pro Gly Pro 
865                 870                 875                 880 

Tyr Ser Met Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe Val Leu 
                885                 890                 895 

Cys Arg Gly Leu Thr Ala Ala Gly Leu Val Ala Met Gly Asp Lys Met 
            900                 905                 910 

Ala Ser His Ile Ser Arg Ala Leu Phe Leu Pro Pro Ile Lys Leu Glu 
        915                 920                 925 

Cys Glu Lys Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys Lys Tyr 
    930                 935                 940 

Ile Gly Val Ile Cys Gly Gly Lys Met Leu Ile Lys Gly Val Asp Leu 
945                 950                 955                 960 

Val Arg Lys Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg Ala Leu 
                965                 970                 975 

Val Asp Leu Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala Ala Ala 
            980                 985                 990 

Leu Ala Glu Arg Pro Ala Glu Glu  Trp Leu Ala Arg Pro  Leu Pro Glu 
        995                 1000                 1005 

Gly Leu  Gln Ala Phe Gly Ala  Val Leu Val Asp Ala  His Arg Arg 
    1010                 1015                 1020 

Ile Thr  Asp Pro Glu Arg Asp  Ile Gln Asp Phe Val  Leu Thr Ala 
    1025                 1030                 1035 

Glu Leu  Ser Arg His Pro Arg  Ala Tyr Thr Asn Lys  Arg Leu Ala 
    1040                 1045                 1050 

His Leu  Thr Val Tyr Tyr Lys  Leu Met Ala Arg Arg  Ala Gln Val 
    1055                 1060                 1065 

Pro Ser  Ile Lys Asp Arg Ile  Pro Tyr Val Ile Val  Ala Gln Thr 
    1070                 1075                 1080 

Arg Glu  Val Glu Glu Thr Val  Ala Arg Leu Ala Ala  Leu Arg Glu 
    1085                 1090                 1095 

Leu Asp  Ala Ala Ala Pro Gly  Asp Glu Pro Ala Pro  Pro Ala Ala 
    1100                 1105                 1110 

Leu Pro  Ser Pro Ala Lys Arg  Pro Arg Glu Thr Pro  Ser His Ala 
    1115                 1120                 1125 

Asp Pro  Pro Gly Gly Ala Ser  Lys Pro Arg Lys Leu  Leu Val Ser 
    1130                 1135                 1140 

Glu Leu  Ala Glu Asp Pro Gly  Tyr Ala Ile Ala Arg  Gly Val Pro 
    1145                 1150                 1155 

Leu Asn  Thr Asp Tyr Tyr Phe  Ser His Leu Leu Gly  Ala Ala Cys 
    1160                 1165                 1170 

Val Thr  Phe Lys Ala Leu Phe  Gly Asn Asn Ala Lys  Ile Thr Glu 
    1175                 1180                 1185 

Ser Leu  Leu Lys Arg Phe Ile  Pro Glu Thr Trp His  Pro Pro Asp 
    1190                 1195                 1200 

Asp Val  Ala Ala Arg Leu Arg  Ala Ala Gly Phe Gly  Pro Ala Gly 
    1205                 1210                 1215 

Ala Gly  Ala Thr Ala Glu Glu  Thr Arg Arg Met Leu  His Arg Ala 
    1220                 1225                 1230 

Phe Asp  Thr Leu Ala 
    1235 

 
           
             3  
             3723  
             DNA  
             herpes simplex  
           
            3 

atgttttgtg ccgcgggcgg cccggcttcc cccgggggga agtcggcggc tcgggcggcg     60 

tctgggtttt ttgcccccca caacccccgg ggagccaccc agacggcacc gccgccttgc    120 

cgccggcaga acttctacaa cccccacctc gctcagaccg gaacgcagcc aaaggccccc    180 

gggccggctc agcgccatac gtactacagc gagtgcgacg aatttcgatt tatcgccccg    240 

cgttcgctgg acgaggacgc ccccgcggag cagcgcaccg gggtccacga cggccgcctc    300 

cggcgcgccc ctaaggtgta ctgcgggggg gacgagcgcg acgtcctccg cgtgggcccg    360 

gagggcttct ggccgcgtcg cttgcgcctg tggggcggtg cggaccatgc ccccgagggg    420 

ttcgacccca ccgtcaccgt cttccacgtg tacgacatcc tggagcacgt ggaacacgcg    480 

tacagcatgc gcgccgccca gctccacgag cgatttatgg acgccatcac gcccgccggg    540 

accgtcatca cgcttctggg tctgaccccc gaaggccatc gcgtcgccgt tcacgtctac    600 

ggcacgcggc agtactttta catgaacaag gcggaggtgg atcggcacct gcagtgccgt    660 

gccccgcgcg atctctgcga gcgcctggcg gcggccctgc gcgagtcgcc gggggcgtcg    720 

ttccgcggca tctccgcgga ccacttcgag gcggaggtgg tggagcgcgc cgacgtgtac    780 

tattacgaaa cgcgcccgac cctgtactac cgcgtcttcg tgcgaagcgg gcgcgcgctg    840 

gcctacctgt gcgacaactt ttgccccgcg atcaggaagt acgagggggg cgtcgacgcc    900 

accacccggt ttatcctgga caacccgggg tttgtcacct tcggctggta ccgcctcaag    960 

cccggccgcg ggaacgcgcc ggcccaaccg cgccccccga cggcgttcgg aacctcgagc   1020 

gacgtcgagt ttaactgcac ggcggacaac ctggccgtcg agggggccat gtgtgacctg   1080 

ccggcctaca agctcatgtg cttcgatatc gaatgcaagg ccggggggga ggacgagctg   1140 

gcctttccgg tcgcggaacg cccggaagac ctcgtcatcc agatctcctg tctgctctac   1200 

gacctgtcca ccaccgccct cgagcacatc ctcctgtttt cgctcggatc ctgcgacctc   1260 

cccgagtccc acctcagcga tctcgcctcc aggggcctgc cggcccccgt cgtcctggag   1320 

tttgacagcg aattcgagat gctgctggcc ttcatgacct tcgtcaagca gtacggcccc   1380 

gagttcgtga ccgggtacaa catcatcaac ttcgactggc ccttcgtcct gaccaagctg   1440 

acggagatct acaaggtccc gctcgacggg tacgggcgca tgaacggccg gggtgtgttc   1500 

cgcgtgtggg acatcggcca gagccacttt cagaagcgca gcaagatcaa ggtgaacggg   1560 

atggtgaaca tcgacatgta cggcatcatc accgacaagg tcaaactctc cagctacaag   1620 

ctgaacgccg tcgccgaggc cgtcttgaag gacaagaaga aggatctgag ctaccgcgac   1680 

atccccgcct actacgcctc cgggcccgcg cagcgcgggg tgatcggcga gtattgtgtg   1740 

caggactcgc tgctggtcgg gcagctgttc ttcaagtttc tgccgcacct ggagctttcc   1800 

gccgtcgcgc gcctggcggg catcaacatc acccgcacca tctacgacgg ccagcagatc   1860 

cgcgtcttca cgtgcctcct gcgccttgcg ggccagaagg gcttcatcct gccggacacc   1920 

caggggcggt ttcggggcct cgacaaggag gcgcccaagc gcccggccgt gcctcggggg   1980 

gaaggggagc ggccggggga cgggaacggg gacgaggata aggacgacga cgaggacggg   2040 

gacgaggacg gggacgagcg cgaggaggtc gcgcgcgaga ccgggggccg gcacgttggg   2100 

taccaggggg cccgggtcct cgaccccacc tccgggtttc acgtcgaccc cgtggtggtg   2160 

tttgactttg ccagcctgta ccccagcatc atccaggccc acaacctgtg cttcagtacg   2220 

ctctccctgc ggcccgaggc cgtcgcgcac ctggaggcgg accgggacta cctggagatc   2280 

gaggtggggg gccgacggct gttcttcgtg aaggcccacg tacgcgagag cctgctgagc   2340 

atcctgctgc gcgactggct ggccatgcga aagcagatcc gctcgcggat cccccagagc   2400 

ccccccgagg aggccgtcct cctcgacaag caacaggccg ccatcaaggt ggtgtgcaac   2460 

tcggtgtacg ggttcaccgg ggcgcagcac ggtcttctgc cctgcctgca cgtggccgcc   2520 

accgtgacga ccatcggccg cgagatgctc ctcgcgacgc gcgcgtacgt gcacgcgcgc   2580 

tgggcggagt tcgatcagct gctggccgac tttccggagg cggccggcat gcgcgccccc   2640 

ggtccgtact ccatgcgcat catctacggg gacacggact ccattttcgt tttgtgccgc   2700 

ggcctcacgg ccgcgggcct ggtggccatg ggcgacaaga tggcgagcca catctcgcgc   2760 

gcgctgttcc tccccccgat caagctcgag tgcgaaaaaa cgttcaccaa gctgctgctc   2820 

atcgccaaga aaaagtacat cggcgtcatc tgcgggggca agatgctcat caagggcgtg   2880 

gatctggtgc gcaaaaacaa ctgcgcgttt atcaaccgca cctccagggc cctggtcgac   2940 

ctgctgtttt acgacgatac cgtatccgga gcggccgccg cgttagccga gcgccccgca   3000 

gaggagtggc tggcgcgacc cctgcccgag ggactgcagg cgttcggggc cgtcctcgta   3060 

gacgcccatc ggcgcatcac cgacccggag agggacatcc aggactttgt cctcaccgcc   3120 

gaactgagca gacacccgcg cgcgtacacc aacaagcgcc tggcccacct gacggtgtat   3180 

tacaagctca tggcccgccg cgcgcaggtc ccgtccatca aggaccggat cccgtacgtg   3240 

atcgtggccc agacccgcga ggtagaggag acggtcgcgc ggctggccgc cctccgcgag   3300 

ctagacgccg ccgccccagg ggacgagccc gcccccccag cggccctgcc ctccccggcc   3360 

aagcgccccc gggagacgcc gtcgcatgcc gaccccccgg gaggcgcgtc caagccccgc   3420 

aagctgctgg tgtccgagct ggcggaggat cccgggtacg ccatcgcccg gggcgttccg   3480 

ctcaacacgg actattactt ctcgcacctg ctgggggcgg cctgcgtgac gttcaaggcc   3540 

ctgtttggaa ataacgccaa gatcaccgag agtctgttaa agaggtttat tcccgagacg   3600 

tggcaccccc cggacgacgt ggccgcgcgg ctcagggccg cggggttcgg gccggcgggg   3660 

gccggcgcta cggcggagga aactcgtcga atgttgcata gagcctttga tactctagca   3720 

tga                                                                 3723 

 
           
             4  
             1240  
             PRT  
             herpes simplex  
           
            4 

Met Phe Cys Ala Ala Gly Gly Pro Ala Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro His Asn Pro Arg Gly Ala 
            20                  25                  30 

Thr Gln Thr Ala Pro Pro Pro Cys Arg Arg Gln Asn Phe Tyr Asn Pro 
        35                  40                  45 

His Leu Ala Gln Thr Gly Thr Gln Pro Lys Ala Pro Gly Pro Ala Gln 
    50                  55                  60 

Arg His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro 
65                  70                  75                  80 

Arg Ser Leu Asp Glu Asp Ala Pro Ala Glu Gln Arg Thr Gly Val His 
                85                  90                  95 

Asp Gly Arg Leu Arg Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu 
            100                 105                 110 

Arg Asp Val Leu Arg Val Gly Pro Glu Gly Phe Trp Pro Arg Arg Leu 
        115                 120                 125 

Arg Leu Trp Gly Gly Ala Asp His Ala Pro Glu Gly Phe Asp Pro Thr 
    130                 135                 140 

Val Thr Val Phe His Val Tyr Asp Ile Leu Glu His Val Glu His Ala 
145                 150                 155                 160 

Tyr Ser Met Arg Ala Ala Gln Leu His Glu Arg Phe Met Asp Ala Ile 
                165                 170                 175 

Thr Pro Ala Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly 
            180                 185                 190 

His Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met 
        195                 200                 205 

Asn Lys Ala Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp 
    210                 215                 220 

Leu Cys Glu Arg Leu Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser 
225                 230                 235                 240 

Phe Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg 
                245                 250                 255 

Ala Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Thr Leu Tyr Tyr Arg Val 
            260                 265                 270 

Phe Val Arg Ser Gly Arg Ala Leu Ala Tyr Leu Cys Asp Asn Phe Cys 
        275                 280                 285 

Pro Ala Ile Arg Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe 
    290                 295                 300 

Ile Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys 
305                 310                 315                 320 

Pro Gly Arg Gly Asn Ala Pro Ala Gln Pro Arg Pro Pro Thr Ala Phe 
                325                 330                 335 

Gly Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala 
            340                 345                 350 

Val Glu Gly Ala Met Cys Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe 
        355                 360                 365 

Asp Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val 
    370                 375                 380 

Ala Glu Arg Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr 
385                 390                 395                 400 

Asp Leu Ser Thr Thr Ala Leu Glu His Ile Leu Leu Phe Ser Leu Gly 
                405                 410                 415 

Ser Cys Asp Leu Pro Glu Ser His Leu Ser Asp Leu Ala Ser Arg Gly 
            420                 425                 430 

Leu Pro Ala Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu 
        435                 440                 445 

Leu Ala Phe Met Thr Phe Val Lys Gln Tyr Gly Pro Glu Phe Val Thr 
    450                 455                 460 

Gly Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Val Leu Thr Lys Leu 
465                 470                 475                 480 

Thr Glu Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly 
                485                 490                 495 

Arg Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys 
            500                 505                 510 

Arg Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly 
        515                 520                 525 

Ile Ile Thr Asp Lys Val Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val 
    530                 535                 540 

Ala Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp 
545                 550                 555                 560 

Ile Pro Ala Tyr Tyr Ala Ser Gly Pro Ala Gln Arg Gly Val Ile Gly 
                565                 570                 575 

Glu Tyr Cys Val Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys 
            580                 585                 590 

Phe Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile 
        595                 600                 605 

Asn Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr 
    610                 615                 620 

Cys Leu Leu Arg Leu Ala Gly Gln Lys Gly Phe Ile Leu Pro Asp Thr 
625                 630                 635                 640 

Gln Gly Arg Phe Arg Gly Leu Asp Lys Glu Ala Pro Lys Arg Pro Ala 
                645                 650                 655 

Val Pro Arg Gly Glu Gly Glu Arg Pro Gly Asp Gly Asn Gly Asp Glu 
            660                 665                 670 

Asp Lys Asp Asp Asp Glu Asp Gly Asp Glu Asp Gly Asp Glu Arg Glu 
        675                 680                 685 

Glu Val Ala Arg Glu Thr Gly Gly Arg His Val Gly Tyr Gln Gly Ala 
    690                 695                 700 

Arg Val Leu Asp Pro Thr Ser Gly Phe His Val Asp Pro Val Val Val 
705                 710                 715                 720 

Phe Asp Phe Ala Ser Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu 
                725                 730                 735 

Cys Phe Ser Thr Leu Ser Leu Arg Pro Glu Ala Val Ala His Leu Glu 
            740                 745                 750 

Ala Asp Arg Asp Tyr Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe 
        755                 760                 765 

Phe Val Lys Ala His Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg 
    770                 775                 780 

Asp Trp Leu Ala Met Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser 
785                 790                 795                 800 

Pro Pro Glu Glu Ala Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys 
                805                 810                 815 

Val Val Cys Asn Ser Val Tyr Gly Phe Thr Gly Ala Gln His Gly Leu 
            820                 825                 830 

Leu Pro Cys Leu His Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu 
        835                 840                 845 

Met Leu Leu Ala Thr Arg Ala Tyr Val His Ala Arg Trp Ala Glu Phe 
    850                 855                 860 

Asp Gln Leu Leu Ala Asp Phe Pro Glu Ala Ala Gly Met Arg Ala Pro 
865                 870                 875                 880 

Gly Pro Tyr Ser Met Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe 
                885                 890                 895 

Val Leu Cys Arg Gly Leu Thr Ala Ala Gly Leu Val Ala Met Gly Asp 
            900                 905                 910 

Lys Met Ala Ser His Ile Ser Arg Ala Leu Phe Leu Pro Pro Ile Lys 
        915                 920                 925 

Leu Glu Cys Glu Lys Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys 
    930                 935                 940 

Lys Tyr Ile Gly Val Ile Cys Gly Gly Lys Met Leu Ile Lys Gly Val 
945                 950                 955                 960 

Asp Leu Val Arg Lys Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg 
                965                 970                 975 

Ala Leu Val Asp Leu Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala 
            980                 985                 990 

Ala Ala Leu Ala Glu Arg Pro Ala  Glu Glu Trp Leu Ala  Arg Pro Leu 
        995                 1000                 1005 

Pro Glu  Gly Leu Gln Ala Phe  Gly Ala Val Leu Val  Asp Ala His 
    1010                 1015                 1020 

Arg Arg  Ile Thr Asp Pro Glu  Arg Asp Ile Gln Asp  Phe Val Leu 
    1025                 1030                 1035 

Thr Ala  Glu Leu Ser Arg His  Pro Arg Ala Tyr Thr  Asn Lys Arg 
    1040                 1045                 1050 

Leu Ala  His Leu Thr Val Tyr  Tyr Lys Leu Met Ala  Arg Arg Ala 
    1055                 1060                 1065 

Gln Val  Pro Ser Ile Lys Asp  Arg Ile Pro Tyr Val  Ile Val Ala 
    1070                 1075                 1080 

Gln Thr  Arg Glu Val Glu Glu  Thr Val Ala Arg Leu  Ala Ala Leu 
    1085                 1090                 1095 

Arg Glu  Leu Asp Ala Ala Ala  Pro Gly Asp Glu Pro  Ala Pro Pro 
    1100                 1105                 1110 

Ala Ala  Leu Pro Ser Pro Ala  Lys Arg Pro Arg Glu  Thr Pro Ser 
    1115                 1120                 1125 

His Ala  Asp Pro Pro Gly Gly  Ala Ser Lys Pro Arg  Lys Leu Leu 
    1130                 1135                 1140 

Val Ser  Glu Leu Ala Glu Asp  Pro Gly Tyr Ala Ile  Ala Arg Gly 
    1145                 1150                 1155 

Val Pro  Leu Asn Thr Asp Tyr  Tyr Phe Ser His Leu  Leu Gly Ala 
    1160                 1165                 1170 

Ala Cys  Val Thr Phe Lys Ala  Leu Phe Gly Asn Asn  Ala Lys Ile 
    1175                 1180                 1185 

Thr Glu  Ser Leu Leu Lys Arg  Phe Ile Pro Glu Thr  Trp His Pro 
    1190                 1195                 1200 

Pro Asp  Asp Val Ala Ala Arg  Leu Arg Ala Ala Gly  Phe Gly Pro 
    1205                 1210                 1215 

Ala Gly  Ala Gly Ala Thr Ala  Glu Glu Thr Arg Arg  Met Leu His 
    1220                 1225                 1230 

Arg Ala  Phe Asp Thr Leu Ala 
    1235                 1240 

 
           
             5  
             3708  
             DNA  
             herpes simplex  
           
            5 

atgttttccg gtggcggcgg cccgctgtcc cccggaggaa agtcggcggc cagggcggcg     60 

tccgggtttt ttgcgcccgc cggccctcgc ggagccggcc ggggaccccc gccttgtttg    120 

aggcaaaact tttacaaccc ctacctcgcc ccagtcggga cgcaacagaa gccgaccggg    180 

ccaacccagc gccatacgta ctatagcgaa tgcgatgaat ttcgattcat cgccccgcgg    240 

gtgctggacg aggatgcccc cccggagaag cgcgccgggg tgcacgacgg tcacctcaag    300 

cgcgccccca aggtgtactg cgggggggac gagcgcgacg tcctccgcgt cgggtcgggc    360 

ggcttctggc cgcggcgctc gcgcctgtgg ggcggcgtgg accacgcccc ggcggggttc    420 

aaccccaccg tcaccgtctt tcacgtgtac gacatcctgg agaacgtgga gcacgcgtac    480 

ggcatgcgcg cggcccagtt ccacgcgcgg tttatggacg ccatcacacc gacggggacc    540 

gtcatcacgc tcctgggcct gactccggaa ggccaccggg tggccgttca cgtttacggc    600 

acgcggcagt acttttacat gaacaaggag gaggttgaca ggcacctaca atgccgcgcc    660 

ccacgagatc tctgcgagcg catggccgcg gccctgcgcg agtccccggg cgcgtcgttc    720 

cgcggcatct ccgcggacca cttcgaggcg gaggtggtgg agcgcaccga cgtgtactac    780 

tacgagacgc gccccgctct gttttaccgc gtctacgtcc gaagcgggcg cgtgctgtcg    840 

tacctgtgcg acaacttctg cccggccatc aagaagtacg agggtggggt cgacgccacc    900 

acccggttca tcctggacaa ccccgggttc gtcaccttcg gctggtaccg tctcaaaccg    960 

ggccggaaca acacgctagc ccagccgcgg gccccgatgg ccttcgggac atccagcgac   1020 

gtcgagttta actgtacggc ggacaacctg gccatcgagg ggggcatgag cgacctaccg   1080 

gcatacaagc tcatgtgctt cgatatcgaa tgcaaggcgg ggggggagga cgagctggcc   1140 

tttccggtgg ccgggcaccc ggaggacctg gttattcaga tatcctgtct gctctacgac   1200 

ctgtccacca ccgccctgga gcacgtcctc ctgttttcgc tcggttcctg cgacctcccc   1260 

gaatcccacc tgaacgagct ggcggccagg ggcctgccca cgcccgtggt tctggaattc   1320 

gacagcgaat tcgagatgct gttggccttc atgacccttg tgaaacagta cggccccgag   1380 

ttcgtgaccg ggtacaacat catcaacttc gactggccct tcttgctggc caagttgacg   1440 

gacatttaca aggtccccct ggacgggtac ggccgcatga acggccgggg cgtgtttcgc   1500 

gtgtgggaca taggccagag ccacttccag aagcgcagca agataaaggt gaacggcatg   1560 

gtgaacatcg acatgtacgg gatcataacc gacaagatca agctctcgag ctacaagctc   1620 

aacgccgtgg ccgaagccgt cctgaaggac aagaagaagg acctgagcta tcgcgacatc   1680 

cccgcctact acgccgccgg gcccgcgcaa cgcggggtga tcggcgagta ctgcatacag   1740 

gattccctgc tggtgggcca gctgtttttt aagtttttgc cccatctgga gctctcggcc   1800 

gtcgcgcgct tggcgggtat taacatcacc cgcaccatct acgacggcca gcagatccgc   1860 

gtctttacgt gcctgctgcg cctggccgac cagaagggct ttattctgcc ggacacccag   1920 

gggcgattta ggggcgccgg gggggaggcg cccaagcgtc cggccgcagc ccgggaggac   1980 

gaggagcggc cagaggagga gggggaggac gaggacgaac gcgaggaggg cgggggcgag   2040 

cgggagccgg agggcgcgcg ggagaccgcc ggccggcacg tggggtacca gggggccagg   2100 

gtccttgacc ccacttccgg gtttcacgtg aaccccgtgg tggtgttcga ctttgccagc   2160 

ctgtacccca gcatcatcca ggcccacaac ctgtgcttca gcacgctctc cctgagggcc   2220 

gacgcagtgg cgcacctgga ggcgggcaag gactacctgg agatcgaggt gggggggcga   2280 

cggctgttct tcgtcaaggc tcacgtgcga gagagcctcc tcagcatcct cctgcgggac   2340 

tggctcgcca tgcgaaagca gatccgctcg cggattcccc agagcagccc cgaggaggcc   2400 

gtgctcctgg acaagcagca ggccgccatc aaggtcgtgt gtaactcggt gtacgggttc   2460 

acgggagcgc agcacggact cctgccgtgc ctgcacgttg ccgcgacggt gacgaccatc   2520 

ggccgcgaga tgctgctcgc gacccgcgag tacgtccacg cgcgctgggc ggccttcgaa   2580 

cagctcctgg ccgatttccc ggaggcggcc gacatgcgcg cccccgggcc ctattccatg   2640 

cgcatcatct acggggacac ggactccata tttgtgctgt gccgcggcct cacggccgcc   2700 

gggctgacgg ccatgggcga caagatggcg agccacatct cgcgcgcgct gtttctgccc   2760 

cccatcaaac tcgagtgcga aaagacgttc accaagctgc tgctgatcgc caagaaaaag   2820 

tacatcggcg tcatctacgg gggtaagatg ctcatcaagg gcgtggatct ggtgcgcaaa   2880 

aacaactgcg cgtttatcaa ccgcacctcc agggccctgg tcgacctgct gttttacgac   2940 

gataccgtat ccggagcggc cgccgcgtta gccgagcgcc ccgcagagga gtggctggcg   3000 

cgacccctgc ccgagggact gcaggcgttc ggggccgtcc tcgtagacgc ccatcggcgc   3060 

atcaccgacc cggagaggga catccaggac tttgtcctca ccgccgaact gagcagacac   3120 

ccgcgcgcgt acaccaacaa gcgcctggcc cacctgacgg tgtattacaa gctcatggcc   3180 

cgccgcgcgc aggtcccgtc catcaaggac cggatcccgt acgtgatcgt ggcccagacc   3240 

cgcgaggtag aggagacggt cgcgcggctg gccgccctcc gcgagctaga cgccgccgcc   3300 

ccaggggacg agcccgcccc ccccgcggcc ctgccctccc cggccaagcg cccccgggag   3360 

acgccgtcgc atgccgaccc cccgggaggc gcgtccaagc cccgcaagct gctggtgtcc   3420 

gagctggccg aggatcccgc atacgccatt gcccacggcg tcgccctgaa cacggactat   3480 

tacttctccc acctgttggg ggcggcgtgc gtgacattca aggccctgtt tgggaataac   3540 

gccaagatca ccgagagtct gttaaaaagg tttattcccg aagtgtggca ccccccggac   3600 

gacgtggccg cgcggctccg ggccgcaggg ttcggggcgg tgggtgccgg cgctacggcg   3660 

gaggaaactc gtcgaatgtt gcatagagcc tttgatactc tagcatga                3708 

 
           
             6  
             1235  
             PRT  
             herpes simplex  
           
            6 

Met Phe Ser Gly Gly Gly Gly Pro Leu Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro Ala Gly Pro Arg Gly Ala 
            20                  25                  30 

Gly Arg Gly Pro Pro Pro Cys Leu Arg Gln Asn Phe Tyr Asn Pro Tyr 
        35                  40                  45 

Leu Ala Pro Val Gly Thr Gln Gln Lys Pro Thr Gly Pro Thr Gln Arg 
    50                  55                  60 

His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro Arg 
65                  70                  75                  80 

Val Leu Asp Glu Asp Ala Pro Pro Glu Lys Arg Ala Gly Val His Asp 
                85                  90                  95 

Gly His Leu Lys Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu Arg 
            100                 105                 110 

Asp Val Leu Arg Val Gly Ser Gly Gly Phe Trp Pro Arg Arg Ser Arg 
        115                 120                 125 

Leu Trp Gly Gly Val Asp His Ala Pro Ala Gly Phe Asn Pro Thr Val 
    130                 135                 140 

Thr Val Phe His Val Tyr Asp Ile Leu Glu Asn Val Glu His Ala Tyr 
145                 150                 155                 160 

Gly Met Arg Ala Ala Gln Phe His Ala Arg Phe Met Asp Ala Ile Thr 
                165                 170                 175 

Pro Thr Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly His 
            180                 185                 190 

Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met Asn 
        195                 200                 205 

Lys Glu Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp Leu 
    210                 215                 220 

Cys Glu Arg Met Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser Phe 
225                 230                 235                 240 

Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg Thr 
                245                 250                 255 

Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Ala Leu Phe Tyr Arg Val Tyr 
            260                 265                 270 

Val Arg Ser Gly Arg Val Leu Ser Tyr Leu Cys Asp Asn Phe Cys Pro 
        275                 280                 285 

Ala Ile Lys Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe Ile 
    290                 295                 300 

Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys Pro 
305                 310                 315                 320 

Gly Arg Asn Asn Thr Leu Ala Gln Pro Arg Ala Pro Met Ala Phe Gly 
                325                 330                 335 

Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala Ile 
            340                 345                 350 

Glu Gly Gly Met Ser Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe Asp 
        355                 360                 365 

Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val Ala 
    370                 375                 380 

Gly His Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr Asp 
385                 390                 395                 400 

Leu Ser Thr Thr Ala Leu Glu His Val Leu Leu Phe Ser Leu Gly Ser 
                405                 410                 415 

Cys Asp Leu Pro Glu Ser His Leu Asn Glu Leu Ala Ala Arg Gly Leu 
            420                 425                 430 

Pro Thr Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu Leu 
        435                 440                 445 

Ala Phe Met Thr Leu Val Lys Gln Tyr Gly Pro Glu Phe Val Thr Gly 
    450                 455                 460 

Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Leu Leu Ala Lys Leu Thr 
465                 470                 475                 480 

Asp Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly Arg 
                485                 490                 495 

Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys Arg 
            500                 505                 510 

Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly Ile 
        515                 520                 525 

Ile Thr Asp Lys Ile Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val Ala 
    530                 535                 540 

Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp Ile 
545                 550                 555                 560 

Pro Ala Tyr Tyr Ala Ala Gly Pro Ala Gln Arg Gly Val Ile Gly Glu 
                565                 570                 575 

Tyr Cys Ile Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys Phe 
            580                 585                 590 

Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile Asn 
        595                 600                 605 

Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr Cys 
    610                 615                 620 

Leu Leu Arg Leu Ala Asp Gln Lys Gly Phe Ile Leu Pro Asp Thr Gln 
625                 630                 635                 640 

Gly Arg Phe Arg Gly Ala Gly Gly Glu Ala Pro Lys Arg Pro Ala Ala 
                645                 650                 655 

Ala Arg Glu Asp Glu Glu Arg Pro Glu Glu Glu Gly Glu Asp Glu Asp 
            660                 665                 670 

Glu Arg Glu Glu Gly Gly Gly Glu Arg Glu Pro Glu Gly Ala Arg Glu 
        675                 680                 685 

Thr Ala Gly Arg His Val Gly Tyr Gln Gly Ala Arg Val Leu Asp Pro 
    690                 695                 700 

Thr Ser Gly Phe His Val Asn Pro Val Val Val Phe Asp Phe Ala Ser 
705                 710                 715                 720 

Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu Cys Phe Ser Thr Leu 
                725                 730                 735 

Ser Leu Arg Ala Asp Ala Val Ala His Leu Glu Ala Gly Lys Asp Tyr 
            740                 745                 750 

Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe Phe Val Lys Ala His 
        755                 760                 765 

Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg Asp Trp Leu Ala Met 
    770                 775                 780 

Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser Ser Pro Glu Glu Ala 
785                 790                 795                 800 

Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys Val Val Cys Asn Ser 
                805                 810                 815 

Val Tyr Gly Phe Thr Gly Ala Gln His Gly Leu Leu Pro Cys Leu His 
            820                 825                 830 

Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu Met Leu Leu Ala Thr 
        835                 840                 845 

Arg Glu Tyr Val His Ala Arg Trp Ala Ala Phe Glu Gln Leu Leu Ala 
    850                 855                 860 

Asp Phe Pro Glu Ala Ala Asp Met Arg Ala Pro Gly Pro Tyr Ser Met 
865                 870                 875                 880 

Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe Val Leu Cys Arg Gly 
                885                 890                 895 

Leu Thr Ala Ala Gly Leu Thr Ala Met Gly Asp Lys Met Ala Ser His 
            900                 905                 910 

Ile Ser Arg Ala Leu Phe Leu Pro Pro Ile Lys Leu Glu Cys Glu Lys 
        915                 920                 925 

Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys Lys Tyr Ile Gly Val 
    930                 935                 940 

Ile Tyr Gly Gly Lys Met Leu Ile Lys Gly Val Asp Leu Val Arg Lys 
945                 950                 955                 960 

Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg Ala Leu Val Asp Leu 
                965                 970                 975 

Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala Ala Ala Leu Ala Glu 
            980                 985                 990 

Arg Pro Ala Glu Glu Trp Leu Ala  Arg Pro Leu Pro Glu  Gly Leu Gln 
        995                 1000                 1005 

Ala Phe  Gly Ala Val Leu Val  Asp Ala His Arg Arg  Ile Thr Asp 
    1010                 1015                 1020 

Pro Glu  Arg Asp Ile Gln Asp  Phe Val Leu Thr Ala  Glu Leu Ser 
    1025                 1030                 1035 

Arg His  Pro Arg Ala Tyr Thr  Asn Lys Arg Leu Ala  His Leu Thr 
    1040                 1045                 1050 

Val Tyr  Tyr Lys Leu Met Ala  Arg Arg Ala Gln Val  Pro Ser Ile 
    1055                 1060                 1065 

Lys Asp  Arg Ile Pro Tyr Val  Ile Val Ala Gln Thr  Arg Glu Val 
    1070                 1075                 1080 

Glu Glu  Thr Val Ala Arg Leu  Ala Ala Leu Arg Glu  Leu Asp Ala 
    1085                 1090                 1095 

Ala Ala  Pro Gly Asp Glu Pro  Ala Pro Pro Ala Ala  Leu Pro Ser 
    1100                 1105                 1110 

Pro Ala  Lys Arg Pro Arg Glu  Thr Pro Ser His Ala  Asp Pro Pro 
    1115                 1120                 1125 

Gly Gly  Ala Ser Lys Pro Arg  Lys Leu Leu Val Ser  Glu Leu Ala 
    1130                 1135                 1140 

Glu Asp  Pro Ala Tyr Ala Ile  Ala His Gly Val Ala  Leu Asn Thr 
    1145                 1150                 1155 

Asp Tyr  Tyr Phe Ser His Leu  Leu Gly Ala Ala Cys  Val Thr Phe 
    1160                 1165                 1170 

Lys Ala  Leu Phe Gly Asn Asn  Ala Lys Ile Thr Glu  Ser Leu Leu 
    1175                 1180                 1185 

Lys Arg  Phe Ile Pro Glu Val  Trp His Pro Pro Asp  Asp Val Ala 
    1190                 1195                 1200 

Ala Arg  Leu Arg Ala Ala Gly  Phe Gly Ala Val Gly  Ala Gly Ala 
    1205                 1210                 1215 

Thr Ala  Glu Glu Thr Arg Arg  Met Leu His Arg Ala  Phe Asp Thr 
    1220                 1225                 1230 

Leu Ala 
    1235 

 
           
             7  
             3708  
             DNA  
             herpes simplex  
           
            7 

atgttttccg gtggcggcgg cccgctgtcc cccggaggaa agtcggcggc cagggcggcg     60 

tccgggtttt ttgcgcccgc cggccctcgc ggagccggcc ggggaccccc gccttgcttg    120 

aggcaaaact tttacaaccc ctacctcgcc ccagtcggga cgcaacagaa gccgaccggg    180 

ccaacccagc gccatacgta ctatagcgaa tgcgatgaat ttcgattcat cgccccgcgg    240 

gtgctggacg aggatgcccc cccggagaag cgcgccgggg tgcacgacgg tcacctcaag    300 

cgcgccccca aggtgtactg cgggggggac gagcgcgacg tcctccgcgt cgggtcgggc    360 

ggcttctggc cgcggcgctc gcgcctgtgg ggcggcgtgg accacgcccc ggcggggttc    420 

aaccccaccg tcaccgtctt tcacgtgtac gacatcctgg agaacgtgga gcacgcgtac    480 

ggcatgcgcg cggcccagtt ccacgcgcgg tttatggacg ccatcacacc gacggggacc    540 

gtcatcacgc tcctgggcct gactccggaa ggccaccggg tggccgttca cgtttacggc    600 

acgcggcagt acttttacat gaacaaggag gaggtcgaca ggcacctaca atgccgcgcc    660 

ccacgagatc tctgcgagcg catggccgcg gccctgcgcg agtccccggg cgcgtcgttc    720 

cgcggcattt ccgcggacca cttcgaggcg gaggtggtgg agcgcaccga cgtgtactac    780 

tacgagacgc gccccgctct gttttaccgc gtctacgtcc gaagcgggcg cgtgctgtcg    840 

tacctgtgcg acaacttctg cccggccatc aagaagtacg agggtggggt cgacgccacc    900 

acccggttca tcctggacaa ccccgggttc gtcaccttcg gctggtaccg tctcaaaccg    960 

ggccggaaca acacgctagc ccagccgcgg gccccgatgg ccttcgggac atccagcgac   1020 

gtcgagttta actgtacggc ggacaacctg gccatcgagg ggggcatgag cgacctaccg   1080 

gcatacaagc tcatgtgctt cgatatcgaa tgcaaggcgg ggggggagga cgagctggcc   1140 

tttccggtgg ccgggcaccc ggaggacctg gtcatccaga tatcctgtct gctctacgac   1200 

ctgtccacca ccgccctgga gcacgtcctc ctgttttcgc tcggttcctg cgacctcccc   1260 

gaatcccacc tgaacgagct ggcggccagg ggcctgccca cgcccgtggt tctggaattc   1320 

gacagcgaat tcgagatgct gttggccttc atgacccttg tgaaacagta cggccccgag   1380 

ttcgtgaccg ggtacaacat catcaacttc gactggccct tcttgctggc caagctgacg   1440 

gacatttaca aggtccccct ggacgggtac ggccgcatga acggccgggg cgtgtttcgc   1500 

gtgtgggaca taggccagag ccacttccag aagcgcagca agataaaggt gaacggcatg   1560 

gtgaacatcg acatgtacgg gattataacc gacaagatca agctctcgag ctacaagctc   1620 

aacgccgtgg ccgaagccgt cctgaaggac aagaagaagg acctgagcta tcgcgacatc   1680 

cccgcctact acgccgccgg gcccgcgcaa cgcggggtga tcggcgagta ctgcatacag   1740 

gattccctgc tggtgggcca gctgtttttt aagtttttgc cccatctgga gctctcggcc   1800 

gtcgcgcgct tggcgggtat taacatcacc cgcaccatct acgacggcca gcagatccgc   1860 

gtctttacgt gcctgctgcg cctggccgac cagaagggct ttattctgcc ggacacccag   1920 

gggcgattta ggggcggcgg gggggaggcg cccaagcgtc cggccgcagc ccgggaggac   1980 

gaggagcggc cagaggagga gggggaggac gaggacgaac gcgaggaggg cgggggcgag   2040 

cgggagccgg agggcgcgcg ggagaccgcc ggccggcacg tggggtacca gggggccagg   2100 

gtccttgacc ccacttccgg gtttcatgtg aaccccgtgg tggtgttcga ctttgccagc   2160 

ctgtacccca gcatcatcca ggcccacaac ctgtgcttca gcacgctctc cctgagggcc   2220 

gacgcagtgg cgcacctgga ggcgggcaag gactacctgg agatcgaggt gggggggcga   2280 

cggctgttct tcgtcaaggc tcacgtgcga gagagcctcc tcagcatcct cctgcgggac   2340 

tggctcgcca tgcgaaagca gatccgctcg cggattcccc agagcagccc cgaggaggcc   2400 

gtgctcctgg acaagcagca ggccgccatc aaggtcgtgt gtaactcggt ttacgggttc   2460 

acgggagcgc agcacggact cctgccgtgc ctgcacgttg ccgcgacggt gacgaccatc   2520 

ggccgcgaga tgctgctcgc gacccgcgag tacgtccacg cgcgctgggc ggccttcgaa   2580 

cagctcctgg ccgatttccc ggaggcggcc gacatgcgcg cccccgggcc ctattccatg   2640 

cgcatcatct acggggacac ggactccatc tttgtgctgt gccgcggcct cacggccgcc   2700 

gggctgacgg ccgtgggcga caagatggcg agccacatct cgcgcgcgct gtttctgtcc   2760 

cccatcaaac tcgagtgcga aaagacgttc accaagctgc tgctgatcgc caagaaaaag   2820 

tacatcggcg tcatctacgg gggtaagatg ctcatcaagg gcgtggatct ggtgcgcaaa   2880 

aacaactgcg cgtttatcaa ccgcacctcc agggccctgg tcgacctgct gttttacgac   2940 

gataccgtat ccggagcggc cgccgcgtta gccgagcgcc ccgcagagga gtggctggcg   3000 

cgacccctgc ccgagggact gcaggcgttc ggggccgtcc tcgtagacgc ccatcggcgc   3060 

atcaccgacc cggagaggga catccaggac tttgtcctca ccgccgaact gagcagacac   3120 

ccgcgcgcgt acaccaacaa gcgcctggcc cacctgacgg tgtattacaa gctcatggcc   3180 

cgccgcgcgc aggtcccgtc catcaaggac cggatcccgt acgtgatcgt ggcccagacc   3240 

cgcgaggtag aggagacggt cgcgcggctg gccgccctcc gcgagctcga cgccgccgcc   3300 

ccaggggacg agcccgcccc ccccgcggcc ctgccctccc cggccaagcg cccccgggag   3360 

acgccgttgc atgccgaccc cccgggaggc gcgtccaagc cccgcaagct gctggtgtcc   3420 

gagctggccg aggatcccgc atacgccatt gcccacggcg tcgccctgaa cacggactat   3480 

tacttctccc acctgttggg ggcggcgtgc gtgacattca aggccctgtt tgggaataac   3540 

gccaagatca ccgagagtct gttaaaaagg tttattcccg aagtgtggca ccccccggac   3600 

gacgtggccg cgcggctccg ggccgcaggg ttcggggcgg tgggtgccgg cgctacggcg   3660 

gaggaaactc gtcgaatgtt gcatagagcc tttgatactc tagcatga                3708 

 
           
             8  
             1235  
             PRT  
             herpes simplex  
           
            8 

Met Phe Ser Gly Gly Gly Gly Pro Leu Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro Ala Gly Pro Arg Gly Ala 
            20                  25                  30 

Gly Arg Gly Pro Pro Pro Cys Leu Arg Gln Asn Phe Tyr Asn Pro Tyr 
        35                  40                  45 

Leu Ala Pro Val Gly Thr Gln Gln Lys Pro Thr Gly Pro Thr Gln Arg 
    50                  55                  60 

His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro Arg 
65                  70                  75                  80 

Val Leu Asp Glu Asp Ala Pro Pro Glu Lys Arg Ala Gly Val His Asp 
                85                  90                  95 

Gly His Leu Lys Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu Arg 
            100                 105                 110 

Asp Val Leu Arg Val Gly Ser Gly Gly Phe Trp Pro Arg Arg Ser Arg 
        115                 120                 125 

Leu Trp Gly Gly Val Asp His Ala Pro Ala Gly Phe Asn Pro Thr Val 
    130                 135                 140 

Thr Val Phe His Val Tyr Asp Ile Leu Glu Asn Val Glu His Ala Tyr 
145                 150                 155                 160 

Gly Met Arg Ala Ala Gln Phe His Ala Arg Phe Met Asp Ala Ile Thr 
                165                 170                 175 

Pro Thr Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly His 
            180                 185                 190 

Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met Asn 
        195                 200                 205 

Lys Glu Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp Leu 
    210                 215                 220 

Cys Glu Arg Met Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser Phe 
225                 230                 235                 240 

Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg Thr 
                245                 250                 255 

Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Ala Leu Phe Tyr Arg Val Tyr 
            260                 265                 270 

Val Arg Ser Gly Arg Val Leu Ser Tyr Leu Cys Asp Asn Phe Cys Pro 
        275                 280                 285 

Ala Ile Lys Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe Ile 
    290                 295                 300 

Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys Pro 
305                 310                 315                 320 

Gly Arg Asn Asn Thr Leu Ala Gln Pro Arg Ala Pro Met Ala Phe Gly 
                325                 330                 335 

Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala Ile 
            340                 345                 350 

Glu Gly Gly Met Ser Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe Asp 
        355                 360                 365 

Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val Ala 
    370                 375                 380 

Gly His Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr Asp 
385                 390                 395                 400 

Leu Ser Thr Thr Ala Leu Glu His Val Leu Leu Phe Ser Leu Gly Ser 
                405                 410                 415 

Cys Asp Leu Pro Glu Ser His Leu Asn Glu Leu Ala Ala Arg Gly Leu 
            420                 425                 430 

Pro Thr Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu Leu 
        435                 440                 445 

Ala Phe Met Thr Leu Val Lys Gln Tyr Gly Pro Glu Phe Val Thr Gly 
    450                 455                 460 

Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Leu Leu Ala Lys Leu Thr 
465                 470                 475                 480 

Asp Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly Arg 
                485                 490                 495 

Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys Arg 
            500                 505                 510 

Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly Ile 
        515                 520                 525 

Ile Thr Asp Lys Ile Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val Ala 
    530                 535                 540 

Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp Ile 
545                 550                 555                 560 

Pro Ala Tyr Tyr Ala Ala Gly Pro Ala Gln Arg Gly Val Ile Gly Glu 
                565                 570                 575 

Tyr Cys Ile Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys Phe 
            580                 585                 590 

Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile Asn 
        595                 600                 605 

Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr Cys 
    610                 615                 620 

Leu Leu Arg Leu Ala Asp Gln Lys Gly Phe Ile Leu Pro Asp Thr Gln 
625                 630                 635                 640 

Gly Arg Phe Arg Gly Gly Gly Gly Glu Ala Pro Lys Arg Pro Ala Ala 
                645                 650                 655 

Ala Arg Glu Asp Glu Glu Arg Pro Glu Glu Glu Gly Glu Asp Glu Asp 
            660                 665                 670 

Glu Arg Glu Glu Gly Gly Gly Glu Arg Glu Pro Glu Gly Ala Arg Glu 
        675                 680                 685 

Thr Ala Gly Arg His Val Gly Tyr Gln Gly Ala Arg Val Leu Asp Pro 
    690                 695                 700 

Thr Ser Gly Phe His Val Asn Pro Val Val Val Phe Asp Phe Ala Ser 
705                 710                 715                 720 

Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu Cys Phe Ser Thr Leu 
                725                 730                 735 

Ser Leu Arg Ala Asp Ala Val Ala His Leu Glu Ala Gly Lys Asp Tyr 
            740                 745                 750 

Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe Phe Val Lys Ala His 
        755                 760                 765 

Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg Asp Trp Leu Ala Met 
    770                 775                 780 

Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser Ser Pro Glu Glu Ala 
785                 790                 795                 800 

Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys Val Val Cys Asn Ser 
                805                 810                 815 

Val Tyr Gly Phe Thr Gly Ala Gln His Gly Leu Leu Pro Cys Leu His 
            820                 825                 830 

Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu Met Leu Leu Ala Thr 
        835                 840                 845 

Arg Glu Tyr Val His Ala Arg Trp Ala Ala Phe Glu Gln Leu Leu Ala 
    850                 855                 860 

Asp Phe Pro Glu Ala Ala Asp Met Arg Ala Pro Gly Pro Tyr Ser Met 
865                 870                 875                 880 

Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe Val Leu Cys Arg Gly 
                885                 890                 895 

Leu Thr Ala Ala Gly Leu Thr Ala Val Gly Asp Lys Met Ala Ser His 
            900                 905                 910 

Ile Ser Arg Ala Leu Phe Leu Ser Pro Ile Lys Leu Glu Cys Glu Lys 
        915                 920                 925 

Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys Lys Tyr Ile Gly Val 
    930                 935                 940 

Ile Tyr Gly Gly Lys Met Leu Ile Lys Gly Val Asp Leu Val Arg Lys 
945                 950                 955                 960 

Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg Ala Leu Val Asp Leu 
                965                 970                 975 

Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala Ala Ala Leu Ala Glu 
            980                 985                 990 

Arg Pro Ala Glu Glu Trp Leu Ala  Arg Pro Leu Pro Glu  Gly Leu Gln 
        995                 1000                 1005 

Ala Phe  Gly Ala Val Leu Val  Asp Ala His Arg Arg  Ile Thr Asp 
    1010                 1015                 1020 

Pro Glu  Arg Asp Ile Gln Asp  Phe Val Leu Thr Ala  Glu Leu Ser 
    1025                 1030                 1035 

Arg His  Pro Arg Ala Tyr Thr  Asn Lys Arg Leu Ala  His Leu Thr 
    1040                 1045                 1050 

Val Tyr  Tyr Lys Leu Met Ala  Arg Arg Ala Gln Val  Pro Ser Ile 
    1055                 1060                 1065 

Lys Asp  Arg Ile Pro Tyr Val  Ile Val Ala Gln Thr  Arg Glu Val 
    1070                 1075                 1080 

Glu Glu  Thr Val Ala Arg Leu  Ala Ala Leu Arg Glu  Leu Asp Ala 
    1085                 1090                 1095 

Ala Ala  Pro Gly Asp Glu Pro  Ala Pro Pro Ala Ala  Leu Pro Ser 
    1100                 1105                 1110 

Pro Ala  Lys Arg Pro Arg Glu  Thr Pro Leu His Ala  Asp Pro Pro 
    1115                 1120                 1125 

Gly Gly  Ala Ser Lys Pro Arg  Lys Leu Leu Val Ser  Glu Leu Ala 
    1130                 1135                 1140 

Glu Asp  Pro Ala Tyr Ala Ile  Ala His Gly Val Ala  Leu Asn Thr 
    1145                 1150                 1155 

Asp Tyr  Tyr Phe Ser His Leu  Leu Gly Ala Ala Cys  Val Thr Phe 
    1160                 1165                 1170 

Lys Ala  Leu Phe Gly Asn Asn  Ala Lys Ile Thr Glu  Ser Leu Leu 
    1175                 1180                 1185 

Lys Arg  Phe Ile Pro Glu Val  Trp His Pro Pro Asp  Asp Val Ala 
    1190                 1195                 1200 

Ala Arg  Leu Arg Ala Ala Gly  Phe Gly Ala Val Gly  Ala Gly Ala 
    1205                 1210                 1215 

Thr Ala  Glu Glu Thr Arg Arg  Met Leu His Arg Ala  Phe Asp Thr 
    1220                 1225                 1230 

Leu Ala 
    1235 

 
           
             9  
             3708  
             DNA  
             herpes simplex  
           
            9 

atgttttccg gtggcggcgg cccgctgtcc cccggaggaa agtcggcggc cagggcggcg     60 

tccgggtttt ttgcgcccgc cggccctcgc ggagccggcc ggggaccccc gccttgtttg    120 

aggcaaaact tttacaaccc ctacctcgcc ccagtcggga cgcaacagaa gccgaccggg    180 

ccaacccagc gccatacgta ctatagcgaa tgcgatgaat ttcgattcat cgccccgcgg    240 

gtgctggacg aggatgcccc cccggagaag cgcgccgggg tgcacgacgg tcacctcaag    300 

cgcgccccca aggtgtactg cgggggggac gagcgcgacg tcctccgcgt cgggtcgggc    360 

ggcttctggc cgcggcgctc gcgcctgtgg ggcggcgtgg accacgcccc ggcggggttc    420 

aaccccaccg tcaccgtctt tcacgtgtat gacatcctgg agaacgtgga gcacgcgtac    480 

ggcatgcgcg cggcccagtt ccacgcgcgg tttatggacg ccatcacacc gacggggacc    540 

gtcatcacgc tcctgggcct gactccggaa ggccaccggg tggccgttca cgtttacggc    600 

acgcggcagt acttttacat gaacaaggag gaggttgaca ggcacctaca atgccgcgcc    660 

ccacgagatc tctgcgagcg catggccgcg gccctgcgcg agtccccggg cgcgtcgttc    720 

cgcggcatct ccgcggacca cttcgaggcg gaggtggtgg agcgcaccga cgtgtactac    780 

tacgagacgc gccccgctct gttttaccgc gtctacgtcc gaagcgggcg cgtgctgtcg    840 

tacctgtgcg acaacttctg cccggccatc aagaagtacg agggtggggt cgacgccacc    900 

acccggttca tcctggacaa ccccgggttc gtcaccttcg gctggtaccg tctcaaaccg    960 

ggccggaaca acacgctagc ccagccgcgg gccccgatgg ccttcgggac atccagcgat   1020 

gtcgagttta actgtacggc ggacaacctg gccatcgagg ggggcatgag cgacctaccg   1080 

gcatacaagc tcatgtgctt cgatatcgaa tgcaaggcgg ggggggagga cgagctggcc   1140 

tttccggtgg ccgggcaccc ggaggacctg gtcatccaga tatcctgtct gctctacgac   1200 

ctgtccacca ccgccctgga gcacgtcctc ctgttttcgc tcggttcctg cgacctcccc   1260 

gaatcccacc tgaacgagct ggcggccagg ggcctgccca cgcccgtggt tctggaattc   1320 

gacagcgaat tcgagatgct gttggccttc atgacccttg tgaaacagta cggccccgag   1380 

ttcgtgaccg ggtacaacat aatcaacttc gactggccct tcttgctggc caagctgacg   1440 

gacatttaca aggtccccct ggacgggtac ggccgcatga acggccgggg cgtgtttcgc   1500 

gtgtgggaca taggccagag ccacttccag aagcgcagca agataaaggt gaacggcatg   1560 

gtgaacatcg acatgtacgg gattataacc gacaagatca agctctcgag ctacaagctc   1620 

aacgccgtgg ccgaagccgt cctgaaggac aagaagaagg acctgagcta tcgcgacatc   1680 

cccacctact acgccgccgg gcccgcgcaa cgcggggtga tcggcgagta ctgcatacag   1740 

gattccctgc tggtgggcca gctgtttttt aagtttttgc cccatctgga gctctcggcc   1800 

gtcgcgcgct tggcgggtat taacatcacc cgcaccatct acgacggcca gcagatccgc   1860 

gtctttacgt gcctgctgcg cctggccgac cagaagggct ttattctgcc ggacacccag   1920 

gggcgattta ggggcgccgg gggggaggcg cccaagcgtc cggccgcagc ccgggaggac   1980 

gaggagcggc cagaggagga gggggaggac gagaacgaac gcgaggaggg cgggggcgag   2040 

cgggagccgg agggcgcgcg ggagaccgcc ggccggcacg tggggtacca gggggccagg   2100 

gtccttgacc ccacttccgg gtttcacgtg aaccccgtgg tggtgttcga ctttgccagc   2160 

ctgtacccca gcatcatcca ggcccacaac ctgtgcttca gcacgctctc cctgagggcc   2220 

gacgcagtgg cgcacctgga ggcgggcaag gactacctgg agatcgaggt gggggggcga   2280 

cggctgttct tcgtcaaggc tcacgtgcga gagagcctcc tcagcatcct cctgcgggac   2340 

tggctcgcca tgcgaaagca gatccgctcg cggattcccc agagcagccc cgaggaggcc   2400 

gtgctcctgg acaagcagca ggccgccatc aaggtcgtgt gtaactcggt ttacgggttc   2460 

acgggagcgc agcacggact cctgccgtgc ctgcacgttg ccgcgacggt gacgaccatc   2520 

ggccgcgaga tgctgctcgc gacccgcgag tacgtccacg cgcgctgggc ggccttcgaa   2580 

cagctcctgg ccgatttccc ggaggcggcc gacatgcgcg cccccgggcc ctattccatg   2640 

cgcatcatct acggggacac ggactccata tttgtgctgt gccgcggcct cacggccgcc   2700 

gggctgacgg ccgtgggcga caagatggcg agccacatct cgcgcgcgct gtttctgccc   2760 

cccatcaaac tcgagtgcga aaagacgttc accaagctgc tgctgatcgc caagaaaaag   2820 

tacatcggcg tcatctacgg gggtaagatg ctcatcaagg gcgtggatct ggtgcgcaaa   2880 

aacaactgcg cgtttatcaa ccgcacctcc agggccctgg tcgacctgct gttttacgac   2940 

gataccgtat ccggagcggc cgccgcgtta gccgagcgcc ccgcagagga gtggctggcg   3000 

cgacccctgc ccgagggact gcaggcgttc ggggccgtcc tcgtagacgc ccatcggcgc   3060 

atcaccgacc cggagaggga catccaggac tttgttctca ccgccgaact gagcagacac   3120 

ccgcgcgcgt acaccaacaa gcgcctggcc cacctgacgg tgtattacaa gctcatggcc   3180 

cgccgcgcgc aggtcccgtc catcaaggac cggatcccgt acgtgatcgt ggcccagacc   3240 

cgcgaggtag aggagacggt cgcgcggctg gccgccctcc gcgagctaga cgccgccgcc   3300 

ccaggggacg agcccgcccc ccccgcggcc ctgccctccc cggccaagcg cccccgggag   3360 

acgccgtcgc ctgccgaccc cccgggaggc gcgtccaagc cccgcaagct gctggtgtcc   3420 

gagctggccg aggatcccgc atacgccatt gcccacggcg tcgccctgaa cacggactat   3480 

tacttctccc acctgttggg ggcggcgtgc gtgacattca aggccctgtt tgggaataac   3540 

gccaagatca ccgagagtct gttaaaaagg tttattcccg aagtgtggca ccccccggac   3600 

gacgtggccg cgcggctccg gaccgcaggg ttcggggcgg tgggtgccgg cgctacggcg   3660 

gaggaaactc gtcgaatgtt gcatagagcc tttgatactc tagcatga                3708 

 
           
             10  
             1235  
             PRT  
             herpes simplex  
           
            10 

Met Phe Ser Gly Gly Gly Gly Pro Leu Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro Ala Gly Pro Arg Gly Ala 
            20                  25                  30 

Gly Arg Gly Pro Pro Pro Cys Leu Arg Gln Asn Phe Tyr Asn Pro Tyr 
        35                  40                  45 

Leu Ala Pro Val Gly Thr Gln Gln Lys Pro Thr Gly Pro Thr Gln Arg 
    50                  55                  60 

His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro Arg 
65                  70                  75                  80 

Val Leu Asp Glu Asp Ala Pro Pro Glu Lys Arg Ala Gly Val His Asp 
                85                  90                  95 

Gly His Leu Lys Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu Arg 
            100                 105                 110 

Asp Val Leu Arg Val Gly Ser Gly Gly Phe Trp Pro Arg Arg Ser Arg 
        115                 120                 125 

Leu Trp Gly Gly Val Asp His Ala Pro Ala Gly Phe Asn Pro Thr Val 
    130                 135                 140 

Thr Val Phe His Val Tyr Asp Ile Leu Glu Asn Val Glu His Ala Tyr 
145                 150                 155                 160 

Gly Met Arg Ala Ala Gln Phe His Ala Arg Phe Met Asp Ala Ile Thr 
                165                 170                 175 

Pro Thr Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly His 
            180                 185                 190 

Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met Asn 
        195                 200                 205 

Lys Glu Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp Leu 
    210                 215                 220 

Cys Glu Arg Met Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser Phe 
225                 230                 235                 240 

Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg Thr 
                245                 250                 255 

Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Ala Leu Phe Tyr Arg Val Tyr 
            260                 265                 270 

Val Arg Ser Gly Arg Val Leu Ser Tyr Leu Cys Asp Asn Phe Cys Pro 
        275                 280                 285 

Ala Ile Lys Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe Ile 
    290                 295                 300 

Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys Pro 
305                 310                 315                 320 

Gly Arg Asn Asn Thr Leu Ala Gln Pro Arg Ala Pro Met Ala Phe Gly 
                325                 330                 335 

Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala Ile 
            340                 345                 350 

Glu Gly Gly Met Ser Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe Asp 
        355                 360                 365 

Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val Ala 
    370                 375                 380 

Gly His Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr Asp 
385                 390                 395                 400 

Leu Ser Thr Thr Ala Leu Glu His Val Leu Leu Phe Ser Leu Gly Ser 
                405                 410                 415 

Cys Asp Leu Pro Glu Ser His Leu Asn Glu Leu Ala Ala Arg Gly Leu 
            420                 425                 430 

Pro Thr Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu Leu 
        435                 440                 445 

Ala Phe Met Thr Leu Val Lys Gln Tyr Gly Pro Glu Phe Val Thr Gly 
    450                 455                 460 

Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Leu Leu Ala Lys Leu Thr 
465                 470                 475                 480 

Asp Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly Arg 
                485                 490                 495 

Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys Arg 
            500                 505                 510 

Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly Ile 
        515                 520                 525 

Ile Thr Asp Lys Ile Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val Ala 
    530                 535                 540 

Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp Ile 
545                 550                 555                 560 

Pro Thr Tyr Tyr Ala Ala Gly Pro Ala Gln Arg Gly Val Ile Gly Glu 
                565                 570                 575 

Tyr Cys Ile Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys Phe 
            580                 585                 590 

Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile Asn 
        595                 600                 605 

Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr Cys 
    610                 615                 620 

Leu Leu Arg Leu Ala Asp Gln Lys Gly Phe Ile Leu Pro Asp Thr Gln 
625                 630                 635                 640 

Gly Arg Phe Arg Gly Ala Gly Gly Glu Ala Pro Lys Arg Pro Ala Ala 
                645                 650                 655 

Ala Arg Glu Asp Glu Glu Arg Pro Glu Glu Glu Gly Glu Asp Glu Asn 
            660                 665                 670 

Glu Arg Glu Glu Gly Gly Gly Glu Arg Glu Pro Glu Gly Ala Arg Glu 
        675                 680                 685 

Thr Ala Gly Arg His Val Gly Tyr Gln Gly Ala Arg Val Leu Asp Pro 
    690                 695                 700 

Thr Ser Gly Phe His Val Asn Pro Val Val Val Phe Asp Phe Ala Ser 
705                 710                 715                 720 

Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu Cys Phe Ser Thr Leu 
                725                 730                 735 

Ser Leu Arg Ala Asp Ala Val Ala His Leu Glu Ala Gly Lys Asp Tyr 
            740                 745                 750 

Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe Phe Val Lys Ala His 
        755                 760                 765 

Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg Asp Trp Leu Ala Met 
    770                 775                 780 

Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser Ser Pro Glu Glu Ala 
785                 790                 795                 800 

Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys Val Val Cys Asn Ser 
                805                 810                 815 

Val Tyr Gly Phe Thr Gly Ala Gln His Gly Leu Leu Pro Cys Leu His 
            820                 825                 830 

Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu Met Leu Leu Ala Thr 
        835                 840                 845 

Arg Glu Tyr Val His Ala Arg Trp Ala Ala Phe Glu Gln Leu Leu Ala 
    850                 855                 860 

Asp Phe Pro Glu Ala Ala Asp Met Arg Ala Pro Gly Pro Tyr Ser Met 
865                 870                 875                 880 

Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe Val Leu Cys Arg Gly 
                885                 890                 895 

Leu Thr Ala Ala Gly Leu Thr Ala Val Gly Asp Lys Met Ala Ser His 
            900                 905                 910 

Ile Ser Arg Ala Leu Phe Leu Pro Pro Ile Lys Leu Glu Cys Glu Lys 
        915                 920                 925 

Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys Lys Tyr Ile Gly Val 
    930                 935                 940 

Ile Tyr Gly Gly Lys Met Leu Ile Lys Gly Val Asp Leu Val Arg Lys 
945                 950                 955                 960 

Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg Ala Leu Val Asp Leu 
                965                 970                 975 

Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala Ala Ala Leu Ala Glu 
            980                 985                 990 

Arg Pro Ala Glu Glu Trp Leu Ala  Arg Pro Leu Pro Glu  Gly Leu Gln 
        995                 1000                 1005 

Ala Phe  Gly Ala Val Leu Val  Asp Ala His Arg Arg  Ile Thr Asp 
    1010                 1015                 1020 

Pro Glu  Arg Asp Ile Gln Asp  Phe Val Leu Thr Ala  Glu Leu Ser 
    1025                 1030                 1035 

Arg His  Pro Arg Ala Tyr Thr  Asn Lys Arg Leu Ala  His Leu Thr 
    1040                 1045                 1050 

Val Tyr  Tyr Lys Leu Met Ala  Arg Arg Ala Gln Val  Pro Ser Ile 
    1055                 1060                 1065 

Lys Asp  Arg Ile Pro Tyr Val  Ile Val Ala Gln Thr  Arg Glu Val 
    1070                 1075                 1080 

Glu Glu  Thr Val Ala Arg Leu  Ala Ala Leu Arg Glu  Leu Asp Ala 
    1085                 1090                 1095 

Ala Ala  Pro Gly Asp Glu Pro  Ala Pro Pro Ala Ala  Leu Pro Ser 
    1100                 1105                 1110 

Pro Ala  Lys Arg Pro Arg Glu  Thr Pro Ser Pro Ala  Asp Pro Pro 
    1115                 1120                 1125 

Gly Gly  Ala Ser Lys Pro Arg  Lys Leu Leu Val Ser  Glu Leu Ala 
    1130                 1135                 1140 

Glu Asp  Pro Ala Tyr Ala Ile  Ala His Gly Val Ala  Leu Asn Thr 
    1145                 1150                 1155 

Asp Tyr  Tyr Phe Ser His Leu  Leu Gly Ala Ala Cys  Val Thr Phe 
    1160                 1165                 1170 

Lys Ala  Leu Phe Gly Asn Asn  Ala Lys Ile Thr Glu  Ser Leu Leu 
    1175                 1180                 1185 

Lys Arg  Phe Ile Pro Glu Val  Trp His Pro Pro Asp  Asp Val Ala 
    1190                 1195                 1200 

Ala Arg  Leu Arg Thr Ala Gly  Phe Gly Ala Val Gly  Ala Gly Ala 
    1205                 1210                 1215 

Thr Ala  Glu Glu Thr Arg Arg  Met Leu His Arg Ala  Phe Asp Thr 
    1220                 1225                 1230 

Leu Ala 
    1235 

 
           
             11  
             3729  
             DNA  
             herpes simplex  
           
            11 

atgtttttca acccgtatct gagcggcggc gtgaccggcg gtgcggtcgc gggtggccgg     60 

cgtcagcgtt cgcagcccgg ctccgcgcag ggctcgggca agcggccgcc acagaaacag    120 

tttttgcaga tcgtgccgcg aggtgtcatg ttcgacggtc agacggggtt gatcaagcat    180 

aagacgggac ggctgcctct catgttctat cgagagatta aacatttgtt gagtcatgac    240 

atggtttggc cgtgtccttg gcgcgagacc ctggtgggtc gcgtggtggg acctattcgt    300 

tttcacacct acgatcagac ggacgccgtg ctcttcttcg actcgcccga aaacgtgtcg    360 

ccgcgctatc gtcagcatct ggtgccttcg gggaacgtgt tgcgtttctt cggggccaca    420 

gaacacggct acagtatctg cgtcaacgtt ttcgggcagc gcagctactt ttactgtgag    480 

tacagcgaca ccgataggct gcgtgaggtc attgccagcg tgggcgaact agtgcccgaa    540 

ccgcggacgc catacgccgt gtctgtcacg ccggccacca agacctccat ctatgggtac    600 

gggacgcgac ccgtgcccga tttgcagtgt gtgtctatca gcaactggac catggccaga    660 

aaaatcggcg agtatctgct ggagcagggt tttcccgtgt acgaggtccg tgtggatccg    720 

ctgacgcgtt tggtcatcga tcggcggatc accacgttcg gctggtgctc cgtgaatcgt    780 

tacgactggc ggcagcaggg tcgcgcgtcg acttgtgata tcgaggtaga ctgcgatgtc    840 

tctgacctgg tggctgtgcc cgacgacagc tcgtggccgc gctatcgatg cctgtccttc    900 

gatatcgagt gcatgagcgg cgagggtggt tttccctgcg ccgagaagtc cgatgacatt    960 

gtcattcaga tctcgtgcgt gtgctacgag acggggggaa acaccgccgt ggatcagggg   1020 

atcccaaacg ggaacgatgg tcggggctgc acttcggagg gtgtgatctt tgggcactcg   1080 

ggtcttcatc tctttacgat cggcacctgc gggcaggtgg gcccagacgt ggacgtctac   1140 

gagttccctt ccgaatacga gctgctgctg ggctttatgc ttttctttca acggtacgcg   1200 

ccggcctttg tgaccggtta caacatcaac tcttttgact tgaagtacat cctcacgcgt   1260 

ctcgagtacc tgtataaggt ggactcgcag cgcttctgca agttgcctac ggcgcagggc   1320 

ggccgtttct ttttacacag ccccgccgtg ggttttaagc ggcagtacgc cgccgctttt   1380 

ccctcggctt ctcacaacaa tccggccagc acggccgcca ccaaggtgta tattgcgggt   1440 

tcggtggtta tcgacatgta ccctgtatgc atggccaaga ctaactcgcc caactataag   1500 

ctcaacacta tggccgagct ttacctgcgg caacgcaagg atgacctgtc ttacaaggac   1560 

atcccgcgtt gtttcgtggc taatgccgag ggccgcgccc aggtaggccg ttactgtctg   1620 

caggacgccg tattggtgcg cgatctgttc aacaccatta attttcacta cgaggccggg   1680 

gccatcgcgc ggctggctaa aattccgttg cggcgtgtca tctttgacgg acagcagatc   1740 

cgtatctaca cctcgctgct ggacgagtgc gcctgccgcg attttatcct gcccaaccac   1800 

tacagcaaag gtacgacggt gcccgaaacg aatagcgttg ctgtgtcacc taacgctgct   1860 

atcatctcta ccgccgctgt gcccggcgac gcgggttctg tggcggctat gtttcagatg   1920 

tcgccgccct tgcaatctgc gccgtccagt caggacggcg tttcacccgg ctccggcagt   1980 

aacagtagta gcagcgtcgg cgttttcagc gtcggctccg gcagtagtgg cggcgtcggc   2040 

gtttccaacg acaatcacgg cgccggcggt actgcggcgg tttcgtacca gggcgccacg   2100 

gtgtttgagc ccgaggtggg ttactacaac gaccccgtgg ccgtgttcga ctttgccagc   2160 

ctctaccctt ccatcatcat ggcccacaac ctctgctact ccaccctgct ggtgccgggt   2220 

ggcgagtacc ctgtggaccc cgccgacgta tacagcgtca cgctagagaa cggcgtgacc   2280 

caccgctttg tgcgtgcttc ggtgcgcgtc tcggtgctct cggaactgct caacaagtgg   2340 

gtttcgcagc ggcgtgccgt gcgcgaatgc atgcgcgagt gtcaagaccc tgtgcgccgt   2400 

atgctgctcg acaaggaaca gatggcgctc aaagtaacgt gcaacgcttt ctacggtttt   2460 

accggcgcgc tgaacggtat gatgccgtgt ctgcccatcg ccgccagcat cacgcgcatc   2520 

ggtcgcgaca tgctagagcg cacggcgcgg ttcatcaaag acaacttttc agagccgtgt   2580 

tttttgcaca atttttttaa tcaggaagac tatgtagtgg gaacgcggga gggggattcg   2640 

gaggagagca gcgcgttacc ggaggggctc gaaacatcgt cagggggctc gaacgaacgg   2700 

cgggtggagg cgcgggtcat ctacggggac acggacagcg tgtttgtccg ctttcgtggc   2760 

ctgacgccgc aggctctggt ggcgcgtggg cccagcctgg cgcactacgt gacggcctgt   2820 

ctttttgtgg agcccgtcaa gctggagttt gaaaaggtct tcgtctctct tatgatgatc   2880 

tgcaagaaac gttacatcgg caaagtggag ggcgcctcgg gtctgagcat gaagggcgtg   2940 

gatctggtgc gcaagacggc ctgcgagttc gtcaagggcg tcacgcgtga cgtcctctcg   3000 

ctgctctttg aggatcgcga ggtctcggaa gcagccgtgc gcctgtcgcg cctctcactc   3060 

gatgaagtca agaagtacgg cgtgccacgc ggtttctggc gtatcttacg ccgcttggtg   3120 

caggcccgcg acgatctgta cctgcaccgt gtgcgtgtcg aggacctggt gctttcgtcg   3180 

gtgctctcta aggacatctc gctgtaccgt caatctaacc tgccgcacat tgccgtcatt   3240 

aagcgattgg cggcccgttc tgaggagcta ccctcggtcg gggatcgggt cttttacgtt   3300 

ctgacggcgc ccggtgtccg gacggcgccg cagggttcct ccgacaacgg tgattctgta   3360 

accgccggcg tggtttcccg gtcggacgcg attgatggca cggacgacga cgctgacggc   3420 

ggcggggtag aggagagcaa caggagagga ggagagccgg caaagaagag ggcgcggaaa   3480 

ccaccgtcgg ccgtgtgcaa ctacgaggta gccgaagatc cgagctacgt gcgcgagcac   3540 

ggcgtgccca ttcacgccga caagtacttt gagcaggttc tcaaggctgt aactaacgtg   3600 

ctgtcgcccg tctttcccgg cggcgaaacc gcgcgcaagg acaagttttt gcacatggtg   3660 

ctgccgcggc gcttgcactt ggagccggct tttctgccgt acagtgtcaa ggcgcacgaa   3720 

tgctgttga                                                           3729 

 
           
             12  
             1242  
             PRT  
             herpes simplex  
           
            12 

Met Phe Phe Asn Pro Tyr Leu Ser Gly Gly Val Thr Gly Gly Ala Val 
1               5                   10                  15 

Ala Gly Gly Arg Arg Gln Arg Ser Gln Pro Gly Ser Ala Gln Gly Ser 
            20                  25                  30 

Gly Lys Arg Pro Pro Gln Lys Gln Phe Leu Gln Ile Val Pro Arg Gly 
        35                  40                  45 

Val Met Phe Asp Gly Gln Thr Gly Leu Ile Lys His Lys Thr Gly Arg 
    50                  55                  60 

Leu Pro Leu Met Phe Tyr Arg Glu Ile Lys His Leu Leu Ser His Asp 
65                  70                  75                  80 

Met Val Trp Pro Cys Pro Trp Arg Glu Thr Leu Val Gly Arg Val Val 
                85                  90                  95 

Gly Pro Ile Arg Phe His Thr Tyr Asp Gln Thr Asp Ala Val Leu Phe 
            100                 105                 110 

Phe Asp Ser Pro Glu Asn Val Ser Pro Arg Tyr Arg Gln His Leu Val 
        115                 120                 125 

Pro Ser Gly Asn Val Leu Arg Phe Phe Gly Ala Thr Glu His Gly Tyr 
    130                 135                 140 

Ser Ile Cys Val Asn Val Phe Gly Gln Arg Ser Tyr Phe Tyr Cys Glu 
145                 150                 155                 160 

Tyr Ser Asp Thr Asp Arg Leu Arg Glu Val Ile Ala Ser Val Gly Glu 
                165                 170                 175 

Leu Val Pro Glu Pro Arg Thr Pro Tyr Ala Val Ser Val Thr Pro Ala 
            180                 185                 190 

Thr Lys Thr Ser Ile Tyr Gly Tyr Gly Thr Arg Pro Val Pro Asp Leu 
        195                 200                 205 

Gln Cys Val Ser Ile Ser Asn Trp Thr Met Ala Arg Lys Ile Gly Glu 
    210                 215                 220 

Tyr Leu Leu Glu Gln Gly Phe Pro Val Tyr Glu Val Arg Val Asp Pro 
225                 230                 235                 240 

Leu Thr Arg Leu Val Ile Asp Arg Arg Ile Thr Thr Phe Gly Trp Cys 
                245                 250                 255 

Ser Val Asn Arg Tyr Asp Trp Arg Gln Gln Gly Arg Ala Ser Thr Cys 
            260                 265                 270 

Asp Ile Glu Val Asp Cys Asp Val Ser Asp Leu Val Ala Val Pro Asp 
        275                 280                 285 

Asp Ser Ser Trp Pro Arg Tyr Arg Cys Leu Ser Phe Asp Ile Glu Cys 
    290                 295                 300 

Met Ser Gly Glu Gly Gly Phe Pro Cys Ala Glu Lys Ser Asp Asp Ile 
305                 310                 315                 320 

Val Ile Gln Ile Ser Cys Val Cys Tyr Glu Thr Gly Gly Asn Thr Ala 
                325                 330                 335 

Val Asp Gln Gly Ile Pro Asn Gly Asn Asp Gly Arg Gly Cys Thr Ser 
            340                 345                 350 

Glu Gly Val Ile Phe Gly His Ser Gly Leu His Leu Phe Thr Ile Gly 
        355                 360                 365 

Thr Cys Gly Gln Val Gly Pro Asp Val Asp Val Tyr Glu Phe Pro Ser 
    370                 375                 380 

Glu Tyr Glu Leu Leu Leu Gly Phe Met Leu Phe Phe Gln Arg Tyr Ala 
385                 390                 395                 400 

Pro Ala Phe Val Thr Gly Tyr Asn Ile Asn Ser Phe Asp Leu Lys Tyr 
                405                 410                 415 

Ile Leu Thr Arg Leu Glu Tyr Leu Tyr Lys Val Asp Ser Gln Arg Phe 
            420                 425                 430 

Cys Lys Leu Pro Thr Ala Gln Gly Gly Arg Phe Phe Leu His Ser Pro 
        435                 440                 445 

Ala Val Gly Phe Lys Arg Gln Tyr Ala Ala Ala Phe Pro Ser Ala Ser 
    450                 455                 460 

His Asn Asn Pro Ala Ser Thr Ala Ala Thr Lys Val Tyr Ile Ala Gly 
465                 470                 475                 480 

Ser Val Val Ile Asp Met Tyr Pro Val Cys Met Ala Lys Thr Asn Ser 
                485                 490                 495 

Pro Asn Tyr Lys Leu Asn Thr Met Ala Glu Leu Tyr Leu Arg Gln Arg 
            500                 505                 510 

Lys Asp Asp Leu Ser Tyr Lys Asp Ile Pro Arg Cys Phe Val Ala Asn 
        515                 520                 525 

Ala Glu Gly Arg Ala Gln Val Gly Arg Tyr Cys Leu Gln Asp Ala Val 
    530                 535                 540 

Leu Val Arg Asp Leu Phe Asn Thr Ile Asn Phe His Tyr Glu Ala Gly 
545                 550                 555                 560 

Ala Ile Ala Arg Leu Ala Lys Ile Pro Leu Arg Arg Val Ile Phe Asp 
                565                 570                 575 

Gly Gln Gln Ile Arg Ile Tyr Thr Ser Leu Leu Asp Glu Cys Ala Cys 
            580                 585                 590 

Arg Asp Phe Ile Leu Pro Asn His Tyr Ser Lys Gly Thr Thr Val Pro 
        595                 600                 605 

Glu Thr Asn Ser Val Ala Val Ser Pro Asn Ala Ala Ile Ile Ser Thr 
    610                 615                 620 

Ala Ala Val Pro Gly Asp Ala Gly Ser Val Ala Ala Met Phe Gln Met 
625                 630                 635                 640 

Ser Pro Pro Leu Gln Ser Ala Pro Ser Ser Gln Asp Gly Val Ser Pro 
                645                 650                 655 

Gly Ser Gly Ser Asn Ser Ser Ser Ser Val Gly Val Phe Ser Val Gly 
            660                 665                 670 

Ser Gly Ser Ser Gly Gly Val Gly Val Ser Asn Asp Asn His Gly Ala 
        675                 680                 685 

Gly Gly Thr Ala Ala Val Ser Tyr Gln Gly Ala Thr Val Phe Glu Pro 
    690                 695                 700 

Glu Val Gly Tyr Tyr Asn Asp Pro Val Ala Val Phe Asp Phe Ala Ser 
705                 710                 715                 720 

Leu Tyr Pro Ser Ile Ile Met Ala His Asn Leu Cys Tyr Ser Thr Leu 
                725                 730                 735 

Leu Val Pro Gly Gly Glu Tyr Pro Val Asp Pro Ala Asp Val Tyr Ser 
            740                 745                 750 

Val Thr Leu Glu Asn Gly Val Thr His Arg Phe Val Arg Ala Ser Val 
        755                 760                 765 

Arg Val Ser Val Leu Ser Glu Leu Leu Asn Lys Trp Val Ser Gln Arg 
    770                 775                 780 

Arg Ala Val Arg Glu Cys Met Arg Glu Cys Gln Asp Pro Val Arg Arg 
785                 790                 795                 800 

Met Leu Leu Asp Lys Glu Gln Met Ala Leu Lys Val Thr Cys Asn Ala 
                805                 810                 815 

Phe Tyr Gly Phe Thr Gly Ala Leu Asn Gly Met Met Pro Cys Leu Pro 
            820                 825                 830 

Ile Ala Ala Ser Ile Thr Arg Ile Gly Arg Asp Met Leu Glu Arg Thr 
        835                 840                 845 

Ala Arg Phe Ile Lys Asp Asn Phe Ser Glu Pro Cys Phe Leu His Asn 
    850                 855                 860 

Phe Phe Asn Gln Glu Asp Tyr Val Val Gly Thr Arg Glu Gly Asp Ser 
865                 870                 875                 880 

Glu Glu Ser Ser Ala Leu Pro Glu Gly Leu Glu Thr Ser Ser Gly Gly 
                885                 890                 895 

Ser Asn Glu Arg Arg Val Glu Ala Arg Val Ile Tyr Gly Asp Thr Asp 
            900                 905                 910 

Ser Val Phe Val Arg Phe Arg Gly Leu Thr Pro Gln Ala Leu Val Ala 
        915                 920                 925 

Arg Gly Pro Ser Leu Ala His Tyr Val Thr Ala Cys Leu Phe Val Glu 
    930                 935                 940 

Pro Val Lys Leu Glu Phe Glu Lys Val Phe Val Ser Leu Met Met Ile 
945                 950                 955                 960 

Cys Lys Lys Arg Tyr Ile Gly Lys Val Glu Gly Ala Ser Gly Leu Ser 
                965                 970                 975 

Met Lys Gly Val Asp Leu Val Arg Lys Thr Ala Cys Glu Phe Val Lys 
            980                 985                 990 

Gly Val Thr Arg Asp Val Leu Ser  Leu Leu Phe Glu Asp  Arg Glu Val 
        995                 1000                 1005 

Ser Glu  Ala Ala Val Arg Leu  Ser Arg Leu Ser Leu  Asp Glu Val 
    1010                 1015                 1020 

Lys Lys  Tyr Gly Val Pro Arg  Gly Phe Trp Arg Ile  Leu Arg Arg 
    1025                 1030                 1035 

Leu Val  Gln Ala Arg Asp Asp  Leu Tyr Leu His Arg  Val Arg Val 
    1040                 1045                 1050 

Glu Asp  Leu Val Leu Ser Ser  Val Leu Ser Lys Asp  Ile Ser Leu 
    1055                 1060                 1065 

Tyr Arg  Gln Ser Asn Leu Pro  His Ile Ala Val Ile  Lys Arg Leu 
    1070                 1075                 1080 

Ala Ala  Arg Ser Glu Glu Leu  Pro Ser Val Gly Asp  Arg Val Phe 
    1085                 1090                 1095 

Tyr Val  Leu Thr Ala Pro Gly  Val Arg Thr Ala Pro  Gln Gly Ser 
    1100                 1105                 1110 

Ser Asp  Asn Gly Asp Ser Val  Thr Ala Gly Val Val  Ser Arg Ser 
    1115                 1120                 1125 

Asp Ala  Ile Asp Gly Thr Asp  Asp Asp Ala Asp Gly  Gly Gly Val 
    1130                 1135                 1140 

Glu Glu  Ser Asn Arg Arg Gly  Gly Glu Pro Ala Lys  Lys Arg Ala 
    1145                 1150                 1155 

Arg Lys  Pro Pro Ser Ala Val  Cys Asn Tyr Glu Val  Ala Glu Asp 
    1160                 1165                 1170 

Pro Ser  Tyr Val Arg Glu His  Gly Val Pro Ile His  Ala Asp Lys 
    1175                 1180                 1185 

Tyr Phe  Glu Gln Val Leu Lys  Ala Val Thr Asn Val  Leu Ser Pro 
    1190                 1195                 1200 

Val Phe  Pro Gly Gly Glu Thr  Ala Arg Lys Asp Lys  Phe Leu His 
    1205                 1210                 1215 

Met Val  Leu Pro Arg Arg Leu  His Leu Glu Pro Ala  Phe Leu Pro 
    1220                 1225                 1230 

Tyr Ser  Val Lys Ala His Glu  Cys Cys 
    1235                 1240 

 
           
             13  
             1242  
             PRT  
             herpes simplex  
           
            13 

Met Phe Phe Asn Pro Tyr Leu Ser Gly Gly Val Thr Gly Gly Ala Val 
1               5                   10                  15 

Ala Gly Gly Arg Arg Gln Arg Ser Gln Pro Gly Ser Ala Gln Gly Ser 
            20                  25                  30 

Gly Lys Arg Pro Pro Gln Lys Gln Phe Leu Gln Ile Val Pro Arg Gly 
        35                  40                  45 

Val Met Phe Asp Gly Gln Thr Gly Leu Ile Lys His Lys Thr Gly Arg 
    50                  55                  60 

Leu Pro Leu Met Phe Tyr Arg Glu Ile Lys His Leu Leu Ser His Asp 
65                  70                  75                  80 

Met Val Trp Pro Cys Pro Trp Arg Glu Thr Leu Val Gly Arg Val Val 
                85                  90                  95 

Gly Pro Ile Arg Phe His Thr Tyr Asp Gln Thr Asp Ala Val Leu Phe 
            100                 105                 110 

Phe Asp Ser Pro Glu Asn Val Ser Pro Arg Tyr Arg Gln His Leu Val 
        115                 120                 125 

Pro Ser Gly Asn Val Leu Arg Phe Phe Gly Ala Thr Glu His Gly Tyr 
    130                 135                 140 

Ser Ile Cys Val Asn Val Phe Gly Gln Arg Ser Tyr Phe Tyr Cys Glu 
145                 150                 155                 160 

Tyr Ser Asp Thr Asp Arg Leu Arg Glu Val Ile Ala Ser Val Gly Glu 
                165                 170                 175 

Leu Val Pro Glu Pro Arg Thr Pro Tyr Ala Val Ser Val Thr Pro Ala 
            180                 185                 190 

Thr Lys Thr Ser Ile Tyr Gly Tyr Gly Thr Arg Pro Val Pro Asp Leu 
        195                 200                 205 

Gln Cys Val Ser Ile Ser Asn Trp Thr Met Ala Arg Lys Ile Gly Glu 
    210                 215                 220 

Tyr Leu Leu Glu Gln Gly Phe Pro Val Tyr Glu Val Arg Val Asp Pro 
225                 230                 235                 240 

Leu Thr Arg Leu Val Ile Asp Arg Arg Ile Thr Thr Phe Gly Trp Cys 
                245                 250                 255 

Ser Val Asn Arg Tyr Asp Trp Arg Gln Gln Gly Arg Ala Ser Thr Cys 
            260                 265                 270 

Asp Ile Glu Val Asp Cys Asp Val Ser Asp Leu Val Ala Val Pro Asp 
        275                 280                 285 

Asp Ser Ser Trp Pro Arg Tyr Arg Cys Leu Ser Phe Asp Ile Glu Cys 
    290                 295                 300 

Met Ser Gly Glu Gly Gly Phe Pro Cys Ala Glu Lys Ser Asp Asp Ile 
305                 310                 315                 320 

Val Ile Gln Ile Ser Cys Val Cys Tyr Glu Thr Gly Gly Asn Thr Ala 
                325                 330                 335 

Val Asp Gln Gly Ile Pro Asn Gly Asn Asp Gly Arg Gly Cys Thr Ser 
            340                 345                 350 

Glu Gly Val Ile Phe Gly His Ser Gly Leu His Leu Phe Thr Ile Gly 
        355                 360                 365 

Thr Cys Gly Gln Val Gly Pro Asp Val Asp Val Tyr Glu Phe Pro Ser 
    370                 375                 380 

Glu Tyr Glu Leu Leu Leu Gly Phe Met Leu Phe Phe Gln Arg Tyr Ala 
385                 390                 395                 400 

Pro Ala Phe Val Thr Gly Tyr Asn Ile Asn Ser Phe Asp Leu Lys Tyr 
                405                 410                 415 

Ile Leu Thr Arg Leu Glu Tyr Leu Tyr Lys Val Asp Ser Gln Arg Phe 
            420                 425                 430 

Cys Lys Leu Pro Thr Ala Gln Gly Gly Arg Phe Phe Leu His Ser Pro 
        435                 440                 445 

Ala Val Gly Phe Lys Arg Gln Tyr Ala Ala Ala Phe Pro Ser Ala Ser 
    450                 455                 460 

His Asn Asn Pro Ala Ser Thr Ala Ala Thr Lys Val Tyr Ile Ala Gly 
465                 470                 475                 480 

Ser Val Val Ile Asp Met Tyr Pro Val Cys Met Ala Lys Thr Asn Ser 
                485                 490                 495 

Pro Asn Tyr Lys Leu Asn Thr Met Ala Glu Leu Tyr Leu Arg Gln Arg 
            500                 505                 510 

Lys Asp Asp Leu Ser Tyr Lys Asp Ile Pro Arg Cys Phe Val Ala Asn 
        515                 520                 525 

Ala Glu Gly Arg Ala Gln Val Gly Arg Tyr Cys Leu Gln Asp Ala Val 
    530                 535                 540 

Leu Val Arg Asp Leu Phe Asn Thr Ile Asn Phe His Tyr Glu Ala Gly 
545                 550                 555                 560 

Ala Ile Ala Arg Leu Ala Lys Ile Pro Leu Arg Arg Val Ile Phe Asp 
                565                 570                 575 

Gly Gln Gln Ile Arg Ile Tyr Thr Ser Leu Leu Asp Glu Cys Ala Cys 
            580                 585                 590 

Arg Asp Phe Ile Leu Pro Asn His Tyr Ser Lys Gly Thr Thr Val Pro 
        595                 600                 605 

Glu Thr Asn Ser Val Ala Val Ser Pro Asn Ala Ala Ile Ile Ser Thr 
    610                 615                 620 

Ala Ala Val Pro Gly Asp Ala Gly Ser Val Ala Ala Met Phe Gln Met 
625                 630                 635                 640 

Ser Pro Pro Leu Gln Ser Ala Pro Ser Ser Gln Asp Gly Val Ser Pro 
                645                 650                 655 

Gly Ser Gly Ser Asn Ser Ser Ser Ser Val Gly Val Phe Ser Val Gly 
            660                 665                 670 

Ser Gly Ser Ser Gly Gly Val Gly Val Ser Asn Asp Asn His Gly Ala 
        675                 680                 685 

Gly Gly Thr Ala Ala Val Ser Tyr Gln Gly Ala Thr Val Phe Glu Pro 
    690                 695                 700 

Glu Val Gly Tyr Tyr Asn Asp Pro Val Ala Val Phe Asp Phe Ala Ser 
705                 710                 715                 720 

Leu Tyr Pro Ser Ile Ile Met Ala His Asn Leu Cys Tyr Ser Thr Leu 
                725                 730                 735 

Leu Val Pro Gly Gly Glu Tyr Pro Val Asp Pro Ala Asp Val Tyr Ser 
            740                 745                 750 

Val Thr Leu Glu Asn Gly Val Thr His Arg Phe Val Arg Ala Ser Val 
        755                 760                 765 

Arg Val Ser Val Leu Ser Glu Leu Leu Asn Lys Trp Val Ser Gln Arg 
    770                 775                 780 

Arg Ala Val Arg Glu Cys Met Arg Glu Cys Gln Asp Pro Val Arg Arg 
785                 790                 795                 800 

Met Leu Leu Asp Lys Glu Gln Met Ala Leu Lys Val Thr Cys Asn Ala 
                805                 810                 815 

Phe Tyr Gly Phe Thr Gly Val Val Asn Gly Met Met Pro Cys Leu Pro 
            820                 825                 830 

Ile Ala Ala Ser Ile Thr Arg Ile Gly Arg Asp Met Leu Glu Arg Thr 
        835                 840                 845 

Ala Arg Phe Ile Lys Asp Asn Phe Ser Glu Pro Cys Phe Leu His Asn 
    850                 855                 860 

Phe Phe Asn Gln Glu Asp Tyr Val Val Gly Thr Arg Glu Gly Asp Ser 
865                 870                 875                 880 

Glu Glu Ser Ser Ala Leu Pro Glu Gly Leu Glu Thr Ser Ser Gly Gly 
                885                 890                 895 

Ser Asn Glu Arg Arg Val Glu Ala Arg Val Ile Tyr Gly Asp Thr Asp 
            900                 905                 910 

Ser Val Phe Val Arg Phe Arg Gly Leu Thr Pro Gln Ala Leu Val Ala 
        915                 920                 925 

Arg Gly Pro Ser Leu Ala His Tyr Val Thr Ala Cys Leu Phe Val Glu 
    930                 935                 940 

Pro Val Lys Leu Glu Phe Glu Lys Val Phe Val Ser Leu Met Met Ile 
945                 950                 955                 960 

Cys Lys Lys Arg Tyr Ile Gly Lys Val Glu Gly Ala Ser Gly Leu Ser 
                965                 970                 975 

Met Lys Gly Val Asp Leu Val Arg Lys Thr Ala Cys Glu Phe Val Lys 
            980                 985                 990 

Gly Val Thr Arg Asp Val Leu Ser  Leu Leu Phe Glu Asp  Arg Glu Val 
        995                 1000                 1005 

Ser Glu  Ala Ala Val Arg Leu  Ser Arg Leu Ser Leu  Asp Glu Val 
    1010                 1015                 1020 

Lys Lys  Tyr Gly Val Pro Arg  Gly Phe Trp Arg Ile  Leu Arg Arg 
    1025                 1030                 1035 

Leu Val  Gln Ala Arg Asp Asp  Leu Tyr Leu His Arg  Val Arg Val 
    1040                 1045                 1050 

Glu Asp  Leu Val Leu Ser Ser  Val Leu Ser Lys Asp  Ile Ser Leu 
    1055                 1060                 1065 

Tyr Arg  Gln Ser Asn Leu Pro  His Ile Ala Val Ile  Lys Arg Leu 
    1070                 1075                 1080 

Ala Ala  Arg Ser Glu Glu Leu  Pro Ser Val Gly Asp  Arg Val Phe 
    1085                 1090                 1095 

Tyr Val  Leu Thr Ala Pro Gly  Val Arg Thr Ala Pro  Gln Gly Ser 
    1100                 1105                 1110 

Ser Asp  Asn Gly Asp Ser Val  Thr Ala Gly Val Val  Ser Arg Ser 
    1115                 1120                 1125 

Asp Ala  Ile Asp Gly Thr Asp  Asp Asp Ala Asp Gly  Gly Gly Val 
    1130                 1135                 1140 

Glu Glu  Ser Asn Arg Arg Gly  Gly Glu Pro Ala Lys  Lys Arg Ala 
    1145                 1150                 1155 

Arg Lys  Pro Pro Ser Ala Val  Cys Asn Tyr Glu Val  Ala Glu Asp 
    1160                 1165                 1170 

Pro Ser  Tyr Val Arg Glu His  Gly Val Pro Ile His  Ala Asp Lys 
    1175                 1180                 1185 

Tyr Phe  Glu Gln Val Leu Lys  Ala Val Thr Asn Val  Leu Ser Pro 
    1190                 1195                 1200 

Val Phe  Pro Gly Gly Glu Thr  Ala Arg Lys Asp Lys  Phe Leu His 
    1205                 1210                 1215 

Met Val  Leu Pro Arg Arg Leu  His Leu Glu Pro Ala  Phe Leu Pro 
    1220                 1225                 1230 

Tyr Ser  Val Lys Ala His Glu  Cys Cys 
    1235                 1240 

 
           
             14  
             1238  
             PRT  
             herpes simplex  
           
            14 

Met Phe Cys Ala Ala Gly Gly Pro Thr Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro His Asn Pro Arg Gly Ala 
            20                  25                  30 

Thr Gln Thr Ala Pro Pro Pro Cys Arg Arg Gln Asn Phe Tyr Asn Pro 
        35                  40                  45 

His Leu Ala Gln Thr Gly Thr Gln Pro Lys Ala Pro Gly Pro Ala Gln 
    50                  55                  60 

Arg His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro 
65                  70                  75                  80 

Arg Ser Leu Asp Glu Asp Ala Pro Ala Glu Gln Arg Thr Gly Val His 
                85                  90                  95 

Asp Gly Arg Leu Arg Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu 
            100                 105                 110 

Arg Asp Val Leu Arg Val Gly Pro Glu Gly Phe Trp Pro Arg Arg Leu 
        115                 120                 125 

Arg Leu Trp Gly Gly Ala Asp His Ala Pro Lys Gly Phe Asp Pro Thr 
    130                 135                 140 

Val Thr Val Phe His Val Tyr Asp Ile Leu Glu His Val Glu His Ala 
145                 150                 155                 160 

Tyr Ser Met Arg Ala Ala Gln Leu His Glu Arg Phe Met Asp Ala Ile 
                165                 170                 175 

Thr Pro Ala Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly 
            180                 185                 190 

His Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met 
        195                 200                 205 

Asn Lys Ala Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp 
    210                 215                 220 

Leu Cys Glu Arg Leu Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser 
225                 230                 235                 240 

Phe Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg 
                245                 250                 255 

Ala Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Thr Leu Tyr Tyr Arg Val 
            260                 265                 270 

Phe Val Arg Ser Gly Arg Ala Leu Ala Tyr Leu Cys Asp Asn Phe Cys 
        275                 280                 285 

Pro Ala Ile Arg Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe 
    290                 295                 300 

Ile Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys 
305                 310                 315                 320 

Pro Gly Arg Gly Asn Ala Pro Ala Gln Pro Arg Pro Pro Thr Ala Phe 
                325                 330                 335 

Gly Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala 
            340                 345                 350 

Val Glu Gly Ala Met Cys Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe 
        355                 360                 365 

Asp Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val 
    370                 375                 380 

Ala Glu Arg Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr 
385                 390                 395                 400 

Asp Leu Ser Thr Thr Ala Leu Glu His Ile Leu Leu Phe Ser Leu Gly 
                405                 410                 415 

Ser Cys Asp Leu Pro Glu Ser His Leu Ser Asp Leu Ala Ser Arg Gly 
            420                 425                 430 

Leu Pro Ala Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu 
        435                 440                 445 

Leu Ala Phe Met Thr Phe Val Lys Gln Tyr Gly Pro Glu Phe Val Thr 
    450                 455                 460 

Gly Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Val Leu Thr Lys Leu 
465                 470                 475                 480 

Thr Glu Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly 
                485                 490                 495 

Arg Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys 
            500                 505                 510 

Arg Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly 
        515                 520                 525 

Ile Ile Thr Asp Lys Val Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val 
    530                 535                 540 

Ala Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp 
545                 550                 555                 560 

Ile Pro Ala Tyr Tyr Ala Ser Gly Pro Ala Gln Arg Gly Val Ile Gly 
                565                 570                 575 

Glu Tyr Cys Val Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys 
            580                 585                 590 

Phe Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile 
        595                 600                 605 

Asn Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr 
    610                 615                 620 

Cys Leu Leu Arg Leu Ala Gly Gln Lys Gly Phe Ile Leu Pro Asp Thr 
625                 630                 635                 640 

Gln Gly Arg Phe Arg Gly Leu Asp Lys Glu Ala Pro Lys Arg Pro Ala 
                645                 650                 655 

Val Pro Arg Gly Glu Gly Glu Arg Pro Gly Asp Gly Asn Gly Asp Glu 
            660                 665                 670 

Asp Lys Asp Asp Asp Glu Asp Glu Asp Gly Asp Glu Arg Glu Glu Val 
        675                 680                 685 

Ala Arg Glu Thr Gly Gly Arg His Val Gly Tyr Gln Gly Ala Arg Val 
    690                 695                 700 

Leu Asp Pro Thr Ser Gly Phe His Val Asp Pro Val Val Val Phe Asp 
705                 710                 715                 720 

Phe Ala Ser Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu Cys Phe 
                725                 730                 735 

Ser Thr Leu Ser Leu Arg Pro Glu Ala Val Ala His Leu Glu Ala Asp 
            740                 745                 750 

Arg Asp Tyr Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe Phe Val 
        755                 760                 765 

Lys Ala His Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg Asp Trp 
    770                 775                 780 

Leu Ala Met Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser Thr Pro 
785                 790                 795                 800 

Glu Glu Ala Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys Val Val 
                805                 810                 815 

Cys Asn Ser Val Tyr Gly Phe Thr Gly Val Gln His Gly Leu Leu Pro 
            820                 825                 830 

Cys Leu His Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu Met Leu 
        835                 840                 845 

Leu Ala Thr Arg Ala Tyr Val His Ala Arg Trp Ala Glu Phe Asp Gln 
    850                 855                 860 

Leu Leu Ala Asp Phe Pro Glu Ala Ala Gly Met Arg Ala Pro Gly Pro 
865                 870                 875                 880 

Tyr Ser Met Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe Val Leu 
                885                 890                 895 

Cys Arg Gly Leu Thr Ala Ala Gly Leu Val Ala Met Gly Asp Lys Met 
            900                 905                 910 

Ala Ser His Ile Ser Arg Ala Leu Phe Leu Pro Pro Ile Lys Leu Glu 
        915                 920                 925 

Cys Glu Lys Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys Lys Tyr 
    930                 935                 940 

Ile Gly Val Ile Cys Gly Gly Lys Met Leu Ile Lys Gly Val Asp Leu 
945                 950                 955                 960 

Val Arg Lys Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg Ala Leu 
                965                 970                 975 

Val Asp Leu Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala Ala Ala 
            980                 985                 990 

Leu Ala Glu Arg Pro Ala Glu Glu  Trp Leu Ala Arg Pro  Leu Pro Glu 
        995                 1000                 1005 

Gly Leu  Gln Ala Phe Gly Ala  Val Leu Val Asp Ala  His Arg Arg 
    1010                 1015                 1020 

Ile Thr  Asp Pro Glu Arg Asp  Ile Gln Asp Phe Val  Leu Thr Ala 
    1025                 1030                 1035 

Glu Leu  Ser Arg His Pro Arg  Ala Tyr Thr Asn Lys  Arg Leu Ala 
    1040                 1045                 1050 

His Leu  Thr Val Tyr Tyr Lys  Leu Met Ala Arg Arg  Ala Gln Val 
    1055                 1060                 1065 

Pro Ser  Ile Lys Asp Arg Ile  Pro Tyr Val Ile Val  Ala Gln Thr 
    1070                 1075                 1080 

Arg Glu  Val Glu Glu Thr Val  Ala Arg Leu Ala Ala  Leu Arg Glu 
    1085                 1090                 1095 

Leu Asp  Ala Ala Ala Pro Gly  Asp Glu Pro Ala Pro  Pro Ala Ala 
    1100                 1105                 1110 

Leu Pro  Ser Pro Ala Lys Arg  Pro Arg Glu Thr Pro  Ser His Ala 
    1115                 1120                 1125 

Asp Pro  Pro Gly Gly Ala Ser  Lys Pro Arg Lys Leu  Leu Val Ser 
    1130                 1135                 1140 

Glu Leu  Ala Glu Asp Pro Gly  Tyr Ala Ile Ala Arg  Gly Val Pro 
    1145                 1150                 1155 

Leu Asn  Thr Asp Tyr Tyr Phe  Ser His Leu Leu Gly  Ala Ala Cys 
    1160                 1165                 1170 

Val Thr  Phe Lys Ala Leu Phe  Gly Asn Asn Ala Lys  Ile Thr Glu 
    1175                 1180                 1185 

Ser Leu  Leu Lys Arg Phe Ile  Pro Glu Thr Trp His  Pro Pro Asp 
    1190                 1195                 1200 

Asp Val  Ala Ala Arg Leu Arg  Ala Ala Gly Phe Gly  Pro Ala Gly 
    1205                 1210                 1215 

Ala Gly  Ala Thr Ala Glu Glu  Thr Arg Arg Met Leu  His Arg Ala 
    1220                 1225                 1230 

Phe Asp  Thr Leu Ala 
    1235 

 
           
             15  
             1240  
             PRT  
             herpes simplex  
           
            15 

Met Phe Cys Ala Ala Gly Gly Pro Ala Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro His Asn Pro Arg Gly Ala 
            20                  25                  30 

Thr Gln Thr Ala Pro Pro Pro Cys Arg Arg Gln Asn Phe Tyr Asn Pro 
        35                  40                  45 

His Leu Ala Gln Thr Gly Thr Gln Pro Lys Ala Pro Gly Pro Ala Gln 
    50                  55                  60 

Arg His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro 
65                  70                  75                  80 

Arg Ser Leu Asp Glu Asp Ala Pro Ala Glu Gln Arg Thr Gly Val His 
                85                  90                  95 

Asp Gly Arg Leu Arg Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu 
            100                 105                 110 

Arg Asp Val Leu Arg Val Gly Pro Glu Gly Phe Trp Pro Arg Arg Leu 
        115                 120                 125 

Arg Leu Trp Gly Gly Ala Asp His Ala Pro Glu Gly Phe Asp Pro Thr 
    130                 135                 140 

Val Thr Val Phe His Val Tyr Asp Ile Leu Glu His Val Glu His Ala 
145                 150                 155                 160 

Tyr Ser Met Arg Ala Ala Gln Leu His Glu Arg Phe Met Asp Ala Ile 
                165                 170                 175 

Thr Pro Ala Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly 
            180                 185                 190 

His Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met 
        195                 200                 205 

Asn Lys Ala Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp 
    210                 215                 220 

Leu Cys Glu Arg Leu Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser 
225                 230                 235                 240 

Phe Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg 
                245                 250                 255 

Ala Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Thr Leu Tyr Tyr Arg Val 
            260                 265                 270 

Phe Val Arg Ser Gly Arg Ala Leu Ala Tyr Leu Cys Asp Asn Phe Cys 
        275                 280                 285 

Pro Ala Ile Arg Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe 
    290                 295                 300 

Ile Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys 
305                 310                 315                 320 

Pro Gly Arg Gly Asn Ala Pro Ala Gln Pro Arg Pro Pro Thr Ala Phe 
                325                 330                 335 

Gly Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala 
            340                 345                 350 

Val Glu Gly Ala Met Cys Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe 
        355                 360                 365 

Asp Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val 
    370                 375                 380 

Ala Glu Arg Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr 
385                 390                 395                 400 

Asp Leu Ser Thr Thr Ala Leu Glu His Ile Leu Leu Phe Ser Leu Gly 
                405                 410                 415 

Ser Cys Asp Leu Pro Glu Ser His Leu Ser Asp Leu Ala Ser Arg Gly 
            420                 425                 430 

Leu Pro Ala Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu 
        435                 440                 445 

Leu Ala Phe Met Thr Phe Val Lys Gln Tyr Gly Pro Glu Phe Val Thr 
    450                 455                 460 

Gly Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Val Leu Thr Lys Leu 
465                 470                 475                 480 

Thr Glu Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly 
                485                 490                 495 

Arg Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys 
            500                 505                 510 

Arg Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly 
        515                 520                 525 

Ile Ile Thr Asp Lys Val Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val 
    530                 535                 540 

Ala Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp 
545                 550                 555                 560 

Ile Pro Ala Tyr Tyr Ala Ser Gly Pro Ala Gln Arg Gly Val Ile Gly 
                565                 570                 575 

Glu Tyr Cys Val Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys 
            580                 585                 590 

Phe Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile 
        595                 600                 605 

Asn Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr 
    610                 615                 620 

Cys Leu Leu Arg Leu Ala Gly Gln Lys Gly Phe Ile Leu Pro Asp Thr 
625                 630                 635                 640 

Gln Gly Arg Phe Arg Gly Leu Asp Lys Glu Ala Pro Lys Arg Pro Ala 
                645                 650                 655 

Val Pro Arg Gly Glu Gly Glu Arg Pro Gly Asp Gly Asn Gly Asp Glu 
            660                 665                 670 

Asp Lys Asp Asp Asp Glu Asp Gly Asp Glu Asp Gly Asp Glu Arg Glu 
        675                 680                 685 

Glu Val Ala Arg Glu Thr Gly Gly Arg His Val Gly Tyr Gln Gly Ala 
    690                 695                 700 

Arg Val Leu Asp Pro Thr Ser Gly Phe His Val Asp Pro Val Val Val 
705                 710                 715                 720 

Phe Asp Phe Ala Ser Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu 
                725                 730                 735 

Cys Phe Ser Thr Leu Ser Leu Arg Pro Glu Ala Val Ala His Leu Glu 
            740                 745                 750 

Ala Asp Arg Asp Tyr Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe 
        755                 760                 765 

Phe Val Lys Ala His Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg 
    770                 775                 780 

Asp Trp Leu Ala Met Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser 
785                 790                 795                 800 

Pro Pro Glu Glu Ala Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys 
                805                 810                 815 

Val Val Cys Asn Ser Val Tyr Gly Phe Thr Gly Val Gln His Gly Leu 
            820                 825                 830 

Leu Pro Cys Leu His Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu 
        835                 840                 845 

Met Leu Leu Ala Thr Arg Ala Tyr Val His Ala Arg Trp Ala Glu Phe 
    850                 855                 860 

Asp Gln Leu Leu Ala Asp Phe Pro Glu Ala Ala Gly Met Arg Ala Pro 
865                 870                 875                 880 

Gly Pro Tyr Ser Met Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe 
                885                 890                 895 

Val Leu Cys Arg Gly Leu Thr Ala Ala Gly Leu Val Ala Met Gly Asp 
            900                 905                 910 

Lys Met Ala Ser His Ile Ser Arg Ala Leu Phe Leu Pro Pro Ile Lys 
        915                 920                 925 

Leu Glu Cys Glu Lys Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys 
    930                 935                 940 

Lys Tyr Ile Gly Val Ile Cys Gly Gly Lys Met Leu Ile Lys Gly Val 
945                 950                 955                 960 

Asp Leu Val Arg Lys Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg 
                965                 970                 975 

Ala Leu Val Asp Leu Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala 
            980                 985                 990 

Ala Ala Leu Ala Glu Arg Pro Ala  Glu Glu Trp Leu Ala  Arg Pro Leu 
        995                 1000                 1005 

Pro Glu  Gly Leu Gln Ala Phe  Gly Ala Val Leu Val  Asp Ala His 
    1010                 1015                 1020 

Arg Arg  Ile Thr Asp Pro Glu  Arg Asp Ile Gln Asp  Phe Val Leu 
    1025                 1030                 1035 

Thr Ala  Glu Leu Ser Arg His  Pro Arg Ala Tyr Thr  Asn Lys Arg 
    1040                 1045                 1050 

Leu Ala  His Leu Thr Val Tyr  Tyr Lys Leu Met Ala  Arg Arg Ala 
    1055                 1060                 1065 

Gln Val  Pro Ser Ile Lys Asp  Arg Ile Pro Tyr Val  Ile Val Ala 
    1070                 1075                 1080 

Gln Thr  Arg Glu Val Glu Glu  Thr Val Ala Arg Leu  Ala Ala Leu 
    1085                 1090                 1095 

Arg Glu  Leu Asp Ala Ala Ala  Pro Gly Asp Glu Pro  Ala Pro Pro 
    1100                 1105                 1110 

Ala Ala  Leu Pro Ser Pro Ala  Lys Arg Pro Arg Glu  Thr Pro Ser 
    1115                 1120                 1125 

His Ala  Asp Pro Pro Gly Gly  Ala Ser Lys Pro Arg  Lys Leu Leu 
    1130                 1135                 1140 

Val Ser  Glu Leu Ala Glu Asp  Pro Gly Tyr Ala Ile  Ala Arg Gly 
    1145                 1150                 1155 

Val Pro  Leu Asn Thr Asp Tyr  Tyr Phe Ser His Leu  Leu Gly Ala 
    1160                 1165                 1170 

Ala Cys  Val Thr Phe Lys Ala  Leu Phe Gly Asn Asn  Ala Lys Ile 
    1175                 1180                 1185 

Thr Glu  Ser Leu Leu Lys Arg  Phe Ile Pro Glu Thr  Trp His Pro 
    1190                 1195                 1200 

Pro Asp  Asp Val Ala Ala Arg  Leu Arg Ala Ala Gly  Phe Gly Pro 
    1205                 1210                 1215 

Ala Gly  Ala Gly Ala Thr Ala  Glu Glu Thr Arg Arg  Met Leu His 
    1220                 1225                 1230 

Arg Ala  Phe Asp Thr Leu Ala 
    1235                 1240 

 
           
             16  
             1235  
             PRT  
             herpes simplex  
           
            16 

Met Phe Ser Gly Gly Gly Gly Pro Leu Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro Ala Gly Pro Arg Gly Ala 
            20                  25                  30 

Gly Arg Gly Pro Pro Pro Cys Leu Arg Gln Asn Phe Tyr Asn Pro Tyr 
        35                  40                  45 

Leu Ala Pro Val Gly Thr Gln Gln Lys Pro Thr Gly Pro Thr Gln Arg 
    50                  55                  60 

His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro Arg 
65                  70                  75                  80 

Val Leu Asp Glu Asp Ala Pro Pro Glu Lys Arg Ala Gly Val His Asp 
                85                  90                  95 

Gly His Leu Lys Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu Arg 
            100                 105                 110 

Asp Val Leu Arg Val Gly Ser Gly Gly Phe Trp Pro Arg Arg Ser Arg 
        115                 120                 125 

Leu Trp Gly Gly Val Asp His Ala Pro Ala Gly Phe Asn Pro Thr Val 
    130                 135                 140 

Thr Val Phe His Val Tyr Asp Ile Leu Glu Asn Val Glu His Ala Tyr 
145                 150                 155                 160 

Gly Met Arg Ala Ala Gln Phe His Ala Arg Phe Met Asp Ala Ile Thr 
                165                 170                 175 

Pro Thr Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly His 
            180                 185                 190 

Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met Asn 
        195                 200                 205 

Lys Glu Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp Leu 
    210                 215                 220 

Cys Glu Arg Met Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser Phe 
225                 230                 235                 240 

Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg Thr 
                245                 250                 255 

Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Ala Leu Phe Tyr Arg Val Tyr 
            260                 265                 270 

Val Arg Ser Gly Arg Val Leu Ser Tyr Leu Cys Asp Asn Phe Cys Pro 
        275                 280                 285 

Ala Ile Lys Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe Ile 
    290                 295                 300 

Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys Pro 
305                 310                 315                 320 

Gly Arg Asn Asn Thr Leu Ala Gln Pro Arg Ala Pro Met Ala Phe Gly 
                325                 330                 335 

Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala Ile 
            340                 345                 350 

Glu Gly Gly Met Ser Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe Asp 
        355                 360                 365 

Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val Ala 
    370                 375                 380 

Gly His Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr Asp 
385                 390                 395                 400 

Leu Ser Thr Thr Ala Leu Glu His Val Leu Leu Phe Ser Leu Gly Ser 
                405                 410                 415 

Cys Asp Leu Pro Glu Ser His Leu Asn Glu Leu Ala Ala Arg Gly Leu 
            420                 425                 430 

Pro Thr Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu Leu 
        435                 440                 445 

Ala Phe Met Thr Leu Val Lys Gln Tyr Gly Pro Glu Phe Val Thr Gly 
    450                 455                 460 

Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Leu Leu Ala Lys Leu Thr 
465                 470                 475                 480 

Asp Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly Arg 
                485                 490                 495 

Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys Arg 
            500                 505                 510 

Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly Ile 
        515                 520                 525 

Ile Thr Asp Lys Ile Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val Ala 
    530                 535                 540 

Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp Ile 
545                 550                 555                 560 

Pro Ala Tyr Tyr Ala Ala Gly Pro Ala Gln Arg Gly Val Ile Gly Glu 
                565                 570                 575 

Tyr Cys Ile Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys Phe 
            580                 585                 590 

Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile Asn 
        595                 600                 605 

Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr Cys 
    610                 615                 620 

Leu Leu Arg Leu Ala Asp Gln Lys Gly Phe Ile Leu Pro Asp Thr Gln 
625                 630                 635                 640 

Gly Arg Phe Arg Gly Ala Gly Gly Glu Ala Pro Lys Arg Pro Ala Ala 
                645                 650                 655 

Ala Arg Glu Asp Glu Glu Arg Pro Glu Glu Glu Gly Glu Asp Glu Asp 
            660                 665                 670 

Glu Arg Glu Glu Gly Gly Gly Glu Arg Glu Pro Glu Gly Ala Arg Glu 
        675                 680                 685 

Thr Ala Gly Arg His Val Gly Tyr Gln Gly Ala Arg Val Leu Asp Pro 
    690                 695                 700 

Thr Ser Gly Phe His Val Asn Pro Val Val Val Phe Asp Phe Ala Ser 
705                 710                 715                 720 

Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu Cys Phe Ser Thr Leu 
                725                 730                 735 

Ser Leu Arg Ala Asp Ala Val Ala His Leu Glu Ala Gly Lys Asp Tyr 
            740                 745                 750 

Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe Phe Val Lys Ala His 
        755                 760                 765 

Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg Asp Trp Leu Ala Met 
    770                 775                 780 

Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser Ser Pro Glu Glu Ala 
785                 790                 795                 800 

Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys Val Val Cys Asn Ser 
                805                 810                 815 

Val Tyr Gly Phe Thr Gly Val Gln His Gly Leu Leu Pro Cys Leu His 
            820                 825                 830 

Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu Met Leu Leu Ala Thr 
        835                 840                 845 

Arg Glu Tyr Val His Ala Arg Trp Ala Ala Phe Glu Gln Leu Leu Ala 
    850                 855                 860 

Asp Phe Pro Glu Ala Ala Asp Met Arg Ala Pro Gly Pro Tyr Ser Met 
865                 870                 875                 880 

Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe Val Leu Cys Arg Gly 
                885                 890                 895 

Leu Thr Ala Ala Gly Leu Thr Ala Met Gly Asp Lys Met Ala Ser His 
            900                 905                 910 

Ile Ser Arg Ala Leu Phe Leu Pro Pro Ile Lys Leu Glu Cys Glu Lys 
        915                 920                 925 

Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys Lys Tyr Ile Gly Val 
    930                 935                 940 

Ile Tyr Gly Gly Lys Met Leu Ile Lys Gly Val Asp Leu Val Arg Lys 
945                 950                 955                 960 

Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg Ala Leu Val Asp Leu 
                965                 970                 975 

Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala Ala Ala Leu Ala Glu 
            980                 985                 990 

Arg Pro Ala Glu Glu Trp Leu Ala  Arg Pro Leu Pro Glu  Gly Leu Gln 
        995                 1000                 1005 

Ala Phe  Gly Ala Val Leu Val  Asp Ala His Arg Arg  Ile Thr Asp 
    1010                 1015                 1020 

Pro Glu  Arg Asp Ile Gln Asp  Phe Val Leu Thr Ala  Glu Leu Ser 
    1025                 1030                 1035 

Arg His  Pro Arg Ala Tyr Thr  Asn Lys Arg Leu Ala  His Leu Thr 
    1040                 1045                 1050 

Val Tyr  Tyr Lys Leu Met Ala  Arg Arg Ala Gln Val  Pro Ser Ile 
    1055                 1060                 1065 

Lys Asp  Arg Ile Pro Tyr Val  Ile Val Ala Gln Thr  Arg Glu Val 
    1070                 1075                 1080 

Glu Glu  Thr Val Ala Arg Leu  Ala Ala Leu Arg Glu  Leu Asp Ala 
    1085                 1090                 1095 

Ala Ala  Pro Gly Asp Glu Pro  Ala Pro Pro Ala Ala  Leu Pro Ser 
    1100                 1105                 1110 

Pro Ala  Lys Arg Pro Arg Glu  Thr Pro Ser His Ala  Asp Pro Pro 
    1115                 1120                 1125 

Gly Gly  Ala Ser Lys Pro Arg  Lys Leu Leu Val Ser  Glu Leu Ala 
    1130                 1135                 1140 

Glu Asp  Pro Ala Tyr Ala Ile  Ala His Gly Val Ala  Leu Asn Thr 
    1145                 1150                 1155 

Asp Tyr  Tyr Phe Ser His Leu  Leu Gly Ala Ala Cys  Val Thr Phe 
    1160                 1165                 1170 

Lys Ala  Leu Phe Gly Asn Asn  Ala Lys Ile Thr Glu  Ser Leu Leu 
    1175                 1180                 1185 

Lys Arg  Phe Ile Pro Glu Val  Trp His Pro Pro Asp  Asp Val Ala 
    1190                 1195                 1200 

Ala Arg  Leu Arg Ala Ala Gly  Phe Gly Ala Val Gly  Ala Gly Ala 
    1205                 1210                 1215 

Thr Ala  Glu Glu Thr Arg Arg  Met Leu His Arg Ala  Phe Asp Thr 
    1220                 1225                 1230 

Leu Ala 
    1235 

 
           
             17  
             1235  
             PRT  
             herpes simplex  
           
            17 

Met Phe Ser Gly Gly Gly Gly Pro Leu Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro Ala Gly Pro Arg Gly Ala 
            20                  25                  30 

Gly Arg Gly Pro Pro Pro Cys Leu Arg Gln Asn Phe Tyr Asn Pro Tyr 
        35                  40                  45 

Leu Ala Pro Val Gly Thr Gln Gln Lys Pro Thr Gly Pro Thr Gln Arg 
    50                  55                  60 

His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro Arg 
65                  70                  75                  80 

Val Leu Asp Glu Asp Ala Pro Pro Glu Lys Arg Ala Gly Val His Asp 
                85                  90                  95 

Gly His Leu Lys Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu Arg 
            100                 105                 110 

Asp Val Leu Arg Val Gly Ser Gly Gly Phe Trp Pro Arg Arg Ser Arg 
        115                 120                 125 

Leu Trp Gly Gly Val Asp His Ala Pro Ala Gly Phe Asn Pro Thr Val 
    130                 135                 140 

Thr Val Phe His Val Tyr Asp Ile Leu Glu Asn Val Glu His Ala Tyr 
145                 150                 155                 160 

Gly Met Arg Ala Ala Gln Phe His Ala Arg Phe Met Asp Ala Ile Thr 
                165                 170                 175 

Pro Thr Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly His 
            180                 185                 190 

Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met Asn 
        195                 200                 205 

Lys Glu Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp Leu 
    210                 215                 220 

Cys Glu Arg Met Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser Phe 
225                 230                 235                 240 

Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg Thr 
                245                 250                 255 

Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Ala Leu Phe Tyr Arg Val Tyr 
            260                 265                 270 

Val Arg Ser Gly Arg Val Leu Ser Tyr Leu Cys Asp Asn Phe Cys Pro 
        275                 280                 285 

Ala Ile Lys Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe Ile 
    290                 295                 300 

Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys Pro 
305                 310                 315                 320 

Gly Arg Asn Asn Thr Leu Ala Gln Pro Arg Ala Pro Met Ala Phe Gly 
                325                 330                 335 

Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala Ile 
            340                 345                 350 

Glu Gly Gly Met Ser Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe Asp 
        355                 360                 365 

Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val Ala 
    370                 375                 380 

Gly His Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr Asp 
385                 390                 395                 400 

Leu Ser Thr Thr Ala Leu Glu His Val Leu Leu Phe Ser Leu Gly Ser 
                405                 410                 415 

Cys Asp Leu Pro Glu Ser His Leu Asn Glu Leu Ala Ala Arg Gly Leu 
            420                 425                 430 

Pro Thr Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu Leu 
        435                 440                 445 

Ala Phe Met Thr Leu Val Lys Gln Tyr Gly Pro Glu Phe Val Thr Gly 
    450                 455                 460 

Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Leu Leu Ala Lys Leu Thr 
465                 470                 475                 480 

Asp Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly Arg 
                485                 490                 495 

Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys Arg 
            500                 505                 510 

Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly Ile 
        515                 520                 525 

Ile Thr Asp Lys Ile Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val Ala 
    530                 535                 540 

Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp Ile 
545                 550                 555                 560 

Pro Ala Tyr Tyr Ala Ala Gly Pro Ala Gln Arg Gly Val Ile Gly Glu 
                565                 570                 575 

Tyr Cys Ile Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys Phe 
            580                 585                 590 

Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile Asn 
        595                 600                 605 

Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr Cys 
    610                 615                 620 

Leu Leu Arg Leu Ala Asp Gln Lys Gly Phe Ile Leu Pro Asp Thr Gln 
625                 630                 635                 640 

Gly Arg Phe Arg Gly Ala Gly Gly Glu Ala Pro Lys Arg Pro Ala Ala 
                645                 650                 655 

Ala Arg Glu Asp Glu Glu Arg Pro Glu Glu Glu Gly Glu Asp Glu Asp 
            660                 665                 670 

Glu Arg Glu Glu Gly Gly Gly Glu Arg Glu Pro Glu Gly Ala Arg Glu 
        675                 680                 685 

Thr Ala Gly Arg His Val Gly Tyr Gln Gly Ala Arg Val Leu Asp Pro 
    690                 695                 700 

Ile Ser Gly Phe His Val Asn Pro Val Val Val Phe Asp Phe Ala Ser 
705                 710                 715                 720 

Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu Cys Phe Ser Thr Leu 
                725                 730                 735 

Ser Leu Arg Ala Asp Ala Val Ala His Leu Glu Ala Gly Lys Asp Tyr 
            740                 745                 750 

Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe Phe Val Lys Ala His 
        755                 760                 765 

Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg Asp Trp Leu Ala Met 
    770                 775                 780 

Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser Ser Pro Glu Glu Ala 
785                 790                 795                 800 

Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys Val Val Cys Asn Ser 
                805                 810                 815 

Val Tyr Gly Phe Thr Gly Val Gln His Gly Leu Leu Pro Cys Leu His 
            820                 825                 830 

Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu Met Leu Leu Ala Thr 
        835                 840                 845 

Arg Glu Tyr Val His Ala Arg Trp Ala Ala Phe Glu Gln Leu Leu Ala 
    850                 855                 860 

Asp Phe Pro Glu Ala Ala Asp Met Arg Ala Pro Gly Pro Tyr Ser Met 
865                 870                 875                 880 

Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe Val Leu Cys Arg Gly 
                885                 890                 895 

Leu Thr Ala Ala Gly Leu Thr Ala Met Gly Asp Lys Met Ala Ser His 
            900                 905                 910 

Ile Ser Arg Ala Leu Phe Leu Pro Pro Ile Lys Leu Glu Cys Glu Lys 
        915                 920                 925 

Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys Lys Tyr Ile Gly Val 
    930                 935                 940 

Ile Tyr Gly Gly Lys Met Leu Ile Lys Gly Val Asp Leu Val Arg Lys 
945                 950                 955                 960 

Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg Ala Leu Val Asp Leu 
                965                 970                 975 

Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala Ala Ala Leu Ala Glu 
            980                 985                 990 

Arg Pro Ala Glu Glu Trp Leu Ala  Arg Pro Leu Pro Glu  Gly Leu Gln 
        995                 1000                 1005 

Ala Phe  Gly Ala Val Leu Val  Asp Ala His Arg Arg  Ile Thr Asp 
    1010                 1015                 1020 

Pro Glu  Arg Asp Ile Gln Asp  Phe Val Leu Thr Ala  Glu Leu Ser 
    1025                 1030                 1035 

Arg His  Pro Arg Ala Tyr Thr  Asn Lys Arg Leu Ala  His Leu Thr 
    1040                 1045                 1050 

Val Tyr  Tyr Lys Leu Met Ala  Arg Arg Ala Gln Val  Pro Ser Ile 
    1055                 1060                 1065 

Lys Asp  Arg Ile Pro Tyr Val  Ile Val Ala Gln Thr  Arg Glu Val 
    1070                 1075                 1080 

Glu Glu  Thr Val Ala Arg Leu  Ala Ala Leu Arg Glu  Leu Asp Ala 
    1085                 1090                 1095 

Ala Ala  Pro Gly Asp Glu Pro  Ala Pro Pro Ala Ala  Leu Pro Ser 
    1100                 1105                 1110 

Pro Ala  Lys Arg Pro Arg Glu  Thr Pro Ser Pro Ala  Asp Pro Pro 
    1115                 1120                 1125 

Gly Gly  Ala Ser Lys Pro Arg  Lys Leu Leu Val Ser  Glu Leu Ala 
    1130                 1135                 1140 

Glu Asp  Pro Ala Tyr Ala Ile  Ala His Gly Val Ala  Leu Asn Thr 
    1145                 1150                 1155 

Asp Tyr  Tyr Phe Ser His Leu  Leu Gly Ala Ala Cys  Val Thr Phe 
    1160                 1165                 1170 

Lys Ala  Leu Phe Gly Asn Asn  Ala Lys Ile Thr Glu  Ser Leu Leu 
    1175                 1180                 1185 

Lys Arg  Phe Ile Pro Glu Val  Trp His Pro Pro Asp  Asp Val Thr 
    1190                 1195                 1200 

Ala Arg  Leu Arg Ala Ala Gly  Phe Gly Ala Val Gly  Ala Gly Ala 
    1205                 1210                 1215 

Thr Ala  Glu Glu Thr Arg Arg  Met Leu His Arg Ala  Phe Asp Thr 
    1220                 1225                 1230 

Leu Ala 
    1235 

 
           
             18  
             1235  
             PRT  
             herpes simplex  
           
            18 

Met Phe Ser Gly Gly Gly Gly Pro Leu Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro Ala Gly Pro Arg Gly Ala 
            20                  25                  30 

Gly Arg Gly Pro Pro Pro Cys Leu Arg Gln Asn Phe Tyr Asn Pro Tyr 
        35                  40                  45 

Leu Ala Pro Val Gly Thr Gln Gln Lys Pro Thr Gly Pro Thr Gln Arg 
    50                  55                  60 

His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro Arg 
65                  70                  75                  80 

Val Leu Asp Glu Asp Ala Pro Pro Glu Lys Arg Ala Gly Val His Asp 
                85                  90                  95 

Gly His Leu Lys Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu Arg 
            100                 105                 110 

Asp Val Leu Arg Val Gly Ser Gly Gly Phe Trp Pro Arg Arg Ser Arg 
        115                 120                 125 

Leu Trp Gly Gly Val Asp His Ala Pro Ala Gly Phe Asn Pro Thr Val 
    130                 135                 140 

Thr Val Phe His Val Tyr Asp Ile Leu Glu Asn Val Glu His Ala Tyr 
145                 150                 155                 160 

Gly Met Arg Ala Ala Gln Phe His Ala Arg Phe Met Asp Ala Ile Thr 
                165                 170                 175 

Pro Thr Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly His 
            180                 185                 190 

Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met Asn 
        195                 200                 205 

Lys Glu Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp Leu 
    210                 215                 220 

Cys Glu Arg Met Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser Phe 
225                 230                 235                 240 

Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg Thr 
                245                 250                 255 

Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Ala Leu Phe Tyr Arg Val Tyr 
            260                 265                 270 

Val Arg Ser Gly Arg Val Leu Ser Tyr Leu Cys Asp Asn Phe Cys Pro 
        275                 280                 285 

Ala Ile Lys Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe Ile 
    290                 295                 300 

Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys Pro 
305                 310                 315                 320 

Gly Arg Asn Asn Thr Leu Ala Gln Pro Arg Ala Pro Met Ala Phe Gly 
                325                 330                 335 

Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala Ile 
            340                 345                 350 

Glu Gly Gly Met Ser Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe Asp 
        355                 360                 365 

Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val Ala 
    370                 375                 380 

Gly His Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr Asp 
385                 390                 395                 400 

Leu Ser Thr Thr Ala Leu Glu His Val Leu Leu Phe Ser Leu Gly Ser 
                405                 410                 415 

Cys Asp Leu Pro Glu Ser His Leu Asn Glu Leu Ala Ala Arg Gly Leu 
            420                 425                 430 

Pro Thr Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu Leu 
        435                 440                 445 

Ala Phe Met Thr Leu Val Lys Gln Tyr Gly Pro Glu Phe Val Thr Gly 
    450                 455                 460 

Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Leu Leu Ala Lys Leu Thr 
465                 470                 475                 480 

Asp Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly Arg 
                485                 490                 495 

Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys Arg 
            500                 505                 510 

Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly Ile 
        515                 520                 525 

Ile Thr Asp Lys Ile Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val Ala 
    530                 535                 540 

Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp Ile 
545                 550                 555                 560 

Pro Thr Tyr Tyr Ala Ala Gly Pro Ala Gln Arg Gly Val Ile Gly Glu 
                565                 570                 575 

Tyr Cys Ile Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys Phe 
            580                 585                 590 

Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile Asn 
        595                 600                 605 

Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr Cys 
    610                 615                 620 

Leu Leu Arg Leu Ala Asp Gln Lys Gly Phe Ile Leu Pro Asp Thr Gln 
625                 630                 635                 640 

Gly Arg Phe Arg Gly Ala Gly Gly Glu Ala Pro Lys Arg Pro Ala Ala 
                645                 650                 655 

Ala Arg Glu Asp Glu Glu Arg Pro Glu Glu Glu Gly Glu Asp Glu Asn 
            660                 665                 670 

Glu Arg Glu Glu Gly Gly Gly Glu Arg Glu Pro Glu Gly Ala Arg Glu 
        675                 680                 685 

Thr Ala Gly Arg His Val Gly Tyr Gln Gly Ala Arg Val Leu Asp Pro 
    690                 695                 700 

Thr Ser Gly Phe His Val Asn Pro Val Val Val Phe Asp Phe Ala Ser 
705                 710                 715                 720 

Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu Cys Phe Ser Thr Leu 
                725                 730                 735 

Ser Leu Arg Ala Asp Ala Val Ala His Leu Glu Ala Gly Lys Asp Tyr 
            740                 745                 750 

Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe Phe Val Lys Ala His 
        755                 760                 765 

Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg Asp Trp Leu Ala Met 
    770                 775                 780 

Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser Ser Pro Glu Glu Ala 
785                 790                 795                 800 

Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys Val Val Cys Asn Ser 
                805                 810                 815 

Val Tyr Gly Phe Thr Gly Val Gln His Gly Leu Leu Pro Cys Leu His 
            820                 825                 830 

Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu Met Leu Leu Ala Thr 
        835                 840                 845 

Arg Glu Tyr Val His Ala Arg Trp Ala Ala Phe Glu Gln Leu Leu Ala 
    850                 855                 860 

Asp Phe Pro Glu Ala Ala Asp Met Arg Ala Pro Gly Pro Tyr Ser Met 
865                 870                 875                 880 

Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe Val Leu Cys Arg Gly 
                885                 890                 895 

Leu Thr Ala Ala Gly Leu Thr Ala Val Gly Asp Lys Met Ala Ser His 
            900                 905                 910 

Ile Ser Arg Ala Leu Phe Leu Pro Pro Ile Lys Leu Glu Cys Glu Lys 
        915                 920                 925 

Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys Lys Tyr Ile Gly Val 
    930                 935                 940 

Ile Tyr Gly Gly Lys Met Leu Ile Lys Gly Val Asp Leu Val Arg Lys 
945                 950                 955                 960 

Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg Ala Leu Val Asp Leu 
                965                 970                 975 

Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala Ala Ala Leu Ala Glu 
            980                 985                 990 

Arg Pro Ala Glu Glu Trp Leu Ala  Arg Pro Leu Pro Glu  Gly Leu Gln 
        995                 1000                 1005 

Ala Phe  Gly Ala Val Leu Val  Asp Ala His Arg Arg  Ile Thr Asp 
    1010                 1015                 1020 

Pro Glu  Arg Asp Ile Gln Asp  Phe Val Leu Thr Ala  Glu Leu Ser 
    1025                 1030                 1035 

Arg His  Pro Arg Ala Tyr Thr  Asn Lys Arg Leu Ala  His Leu Thr 
    1040                 1045                 1050 

Val Tyr  Tyr Lys Leu Met Ala  Arg Arg Ala Gln Val  Pro Ser Ile 
    1055                 1060                 1065 

Lys Asp  Arg Ile Pro Tyr Val  Ile Val Ala Gln Thr  Arg Glu Val 
    1070                 1075                 1080 

Glu Glu  Thr Val Ala Arg Leu  Ala Ala Leu Arg Glu  Leu Asp Ala 
    1085                 1090                 1095 

Ala Ala  Pro Gly Asp Glu Pro  Ala Pro Pro Ala Ala  Leu Pro Ser 
    1100                 1105                 1110 

Pro Ala  Lys Arg Pro Arg Glu  Thr Pro Ser Pro Ala  Asp Pro Pro 
    1115                 1120                 1125 

Gly Gly  Ala Ser Lys Pro Arg  Lys Leu Leu Val Ser  Glu Leu Ala 
    1130                 1135                 1140 

Glu Asp  Pro Ala Tyr Ala Ile  Ala His Gly Val Ala  Leu Asn Thr 
    1145                 1150                 1155 

Asp Tyr  Tyr Phe Ser His Leu  Leu Gly Ala Ala Cys  Val Thr Phe 
    1160                 1165                 1170 

Lys Ala  Leu Phe Gly Asn Asn  Ala Lys Ile Thr Glu  Ser Leu Leu 
    1175                 1180                 1185 

Lys Arg  Phe Ile Pro Glu Val  Trp His Pro Pro Asp  Asp Val Ala 
    1190                 1195                 1200 

Ala Arg  Leu Arg Thr Ala Gly  Phe Gly Ala Val Gly  Ala Gly Ala 
    1205                 1210                 1215 

Thr Ala  Glu Glu Thr Arg Arg  Met Leu His Arg Ala  Phe Asp Thr 
    1220                 1225                 1230 

Leu Ala 
    1235 

 
           
             19  
             1235  
             PRT  
             herpes simplex  
           
            19 

Met Phe Ser Gly Gly Gly Gly Pro Leu Ser Pro Gly Gly Lys Ser Ala 
1               5                   10                  15 

Ala Arg Ala Ala Ser Gly Phe Phe Ala Pro Ala Gly Pro Arg Gly Ala 
            20                  25                  30 

Gly Arg Gly Pro Pro Pro Cys Leu Arg Gln Asn Phe Tyr Asn Pro Tyr 
        35                  40                  45 

Leu Ala Pro Val Gly Thr Gln Gln Lys Pro Thr Gly Pro Thr Gln Arg 
    50                  55                  60 

His Thr Tyr Tyr Ser Glu Cys Asp Glu Phe Arg Phe Ile Ala Pro Arg 
65                  70                  75                  80 

Val Leu Asp Glu Asp Ala Pro Pro Glu Lys Arg Ala Gly Val His Asp 
                85                  90                  95 

Gly His Leu Lys Arg Ala Pro Lys Val Tyr Cys Gly Gly Asp Glu Arg 
            100                 105                 110 

Asp Val Leu Arg Val Gly Ser Gly Gly Phe Trp Pro Arg Arg Ser Arg 
        115                 120                 125 

Leu Trp Gly Gly Val Asp His Ala Pro Ala Gly Phe Asn Pro Thr Val 
    130                 135                 140 

Thr Val Phe His Val Tyr Asp Ile Leu Glu Asn Val Glu His Ala Tyr 
145                 150                 155                 160 

Gly Met Arg Ala Ala Gln Phe His Ala Arg Phe Met Asp Ala Ile Thr 
                165                 170                 175 

Pro Thr Gly Thr Val Ile Thr Leu Leu Gly Leu Thr Pro Glu Gly His 
            180                 185                 190 

Arg Val Ala Val His Val Tyr Gly Thr Arg Gln Tyr Phe Tyr Met Asn 
        195                 200                 205 

Lys Glu Glu Val Asp Arg His Leu Gln Cys Arg Ala Pro Arg Asp Leu 
    210                 215                 220 

Cys Glu Arg Met Ala Ala Ala Leu Arg Glu Ser Pro Gly Ala Ser Phe 
225                 230                 235                 240 

Arg Gly Ile Ser Ala Asp His Phe Glu Ala Glu Val Val Glu Arg Thr 
                245                 250                 255 

Asp Val Tyr Tyr Tyr Glu Thr Arg Pro Ala Leu Phe Tyr Arg Val Tyr 
            260                 265                 270 

Val Arg Ser Gly Arg Val Leu Ser Tyr Leu Cys Asp Asn Phe Cys Pro 
        275                 280                 285 

Ala Ile Lys Lys Tyr Glu Gly Gly Val Asp Ala Thr Thr Arg Phe Ile 
    290                 295                 300 

Leu Asp Asn Pro Gly Phe Val Thr Phe Gly Trp Tyr Arg Leu Lys Pro 
305                 310                 315                 320 

Gly Arg Asn Asn Thr Leu Ala Gln Pro Arg Ala Pro Met Ala Phe Gly 
                325                 330                 335 

Thr Ser Ser Asp Val Glu Phe Asn Cys Thr Ala Asp Asn Leu Ala Ile 
            340                 345                 350 

Glu Gly Gly Met Ser Asp Leu Pro Ala Tyr Lys Leu Met Cys Phe Asp 
        355                 360                 365 

Ile Glu Cys Lys Ala Gly Gly Glu Asp Glu Leu Ala Phe Pro Val Ala 
    370                 375                 380 

Gly His Pro Glu Asp Leu Val Ile Gln Ile Ser Cys Leu Leu Tyr Asp 
385                 390                 395                 400 

Leu Ser Thr Thr Ala Leu Glu His Val Leu Leu Phe Ser Leu Gly Ser 
                405                 410                 415 

Cys Asp Leu Pro Glu Ser His Leu Asn Glu Leu Ala Ala Arg Gly Leu 
            420                 425                 430 

Pro Thr Pro Val Val Leu Glu Phe Asp Ser Glu Phe Glu Met Leu Leu 
        435                 440                 445 

Ala Phe Met Thr Leu Val Lys Gln Tyr Gly Pro Glu Phe Val Thr Gly 
    450                 455                 460 

Tyr Asn Ile Ile Asn Phe Asp Trp Pro Phe Leu Leu Ala Lys Leu Thr 
465                 470                 475                 480 

Asp Ile Tyr Lys Val Pro Leu Asp Gly Tyr Gly Arg Met Asn Gly Arg 
                485                 490                 495 

Gly Val Phe Arg Val Trp Asp Ile Gly Gln Ser His Phe Gln Lys Arg 
            500                 505                 510 

Ser Lys Ile Lys Val Asn Gly Met Val Asn Ile Asp Met Tyr Gly Ile 
        515                 520                 525 

Ile Thr Asp Lys Ile Lys Leu Ser Ser Tyr Lys Leu Asn Ala Val Ala 
    530                 535                 540 

Glu Ala Val Leu Lys Asp Lys Lys Lys Asp Leu Ser Tyr Arg Asp Ile 
545                 550                 555                 560 

Pro Ala Tyr Tyr Ala Ala Gly Pro Ala Gln Arg Gly Val Ile Gly Glu 
                565                 570                 575 

Tyr Cys Ile Gln Asp Ser Leu Leu Val Gly Gln Leu Phe Phe Lys Phe 
            580                 585                 590 

Leu Pro His Leu Glu Leu Ser Ala Val Ala Arg Leu Ala Gly Ile Asn 
        595                 600                 605 

Ile Thr Arg Thr Ile Tyr Asp Gly Gln Gln Ile Arg Val Phe Thr Cys 
    610                 615                 620 

Leu Leu Arg Leu Ala Asp Gln Lys Gly Phe Ile Leu Pro Asp Thr Gln 
625                 630                 635                 640 

Gly Arg Phe Arg Gly Gly Gly Gly Glu Ala Pro Lys Arg Pro Ala Ala 
                645                 650                 655 

Ala Arg Glu Asp Glu Glu Arg Pro Glu Glu Glu Gly Glu Asp Glu Asp 
            660                 665                 670 

Glu Arg Glu Glu Gly Gly Gly Glu Arg Glu Pro Glu Gly Ala Arg Glu 
        675                 680                 685 

Thr Ala Gly Arg His Val Gly Tyr Gln Gly Ala Arg Val Leu Asp Pro 
    690                 695                 700 

Thr Ser Gly Phe His Val Asn Pro Val Val Val Phe Asp Phe Ala Ser 
705                 710                 715                 720 

Leu Tyr Pro Ser Ile Ile Gln Ala His Asn Leu Cys Phe Ser Thr Leu 
                725                 730                 735 

Ser Leu Arg Ala Asp Ala Val Ala His Leu Glu Ala Gly Lys Asp Tyr 
            740                 745                 750 

Leu Glu Ile Glu Val Gly Gly Arg Arg Leu Phe Phe Val Lys Ala His 
        755                 760                 765 

Val Arg Glu Ser Leu Leu Ser Ile Leu Leu Arg Asp Trp Leu Ala Met 
    770                 775                 780 

Arg Lys Gln Ile Arg Ser Arg Ile Pro Gln Ser Ser Pro Glu Glu Ala 
785                 790                 795                 800 

Val Leu Leu Asp Lys Gln Gln Ala Ala Ile Lys Val Val Cys Asn Ser 
                805                 810                 815 

Val Tyr Gly Phe Thr Gly Val Gln His Gly Leu Leu Pro Cys Leu His 
            820                 825                 830 

Val Ala Ala Thr Val Thr Thr Ile Gly Arg Glu Met Leu Leu Ala Thr 
        835                 840                 845 

Arg Glu Tyr Val His Ala Arg Trp Ala Ala Phe Glu Gln Leu Leu Ala 
    850                 855                 860 

Asp Phe Pro Glu Ala Ala Asp Met Arg Ala Pro Gly Pro Tyr Ser Met 
865                 870                 875                 880 

Arg Ile Ile Tyr Gly Asp Thr Asp Ser Ile Phe Val Leu Cys Arg Gly 
                885                 890                 895 

Leu Thr Ala Ala Gly Leu Thr Ala Val Gly Asp Lys Met Ala Ser His 
            900                 905                 910 

Ile Ser Arg Ala Leu Phe Leu Ser Pro Ile Lys Leu Glu Cys Glu Lys 
        915                 920                 925 

Thr Phe Thr Lys Leu Leu Leu Ile Ala Lys Lys Lys Tyr Ile Gly Val 
    930                 935                 940 

Ile Tyr Gly Gly Lys Met Leu Ile Lys Gly Val Asp Leu Val Arg Lys 
945                 950                 955                 960 

Asn Asn Cys Ala Phe Ile Asn Arg Thr Ser Arg Ala Leu Val Asp Leu 
                965                 970                 975 

Leu Phe Tyr Asp Asp Thr Val Ser Gly Ala Ala Ala Ala Leu Ala Glu 
            980                 985                 990 

Arg Pro Ala Glu Glu Trp Leu Ala  Arg Pro Leu Pro Glu  Gly Leu Gln 
        995                 1000                 1005 

Ala Phe  Gly Ala Val Leu Val  Asp Ala His Arg Arg  Ile Thr Asp 
    1010                 1015                 1020 

Pro Glu  Arg Asp Ile Gln Asp  Phe Val Leu Thr Ala  Glu Leu Ser 
    1025                 1030                 1035 

Arg His  Pro Arg Ala Tyr Thr  Asn Lys Arg Leu Ala  His Leu Thr 
    1040                 1045                 1050 

Val Tyr  Tyr Lys Leu Met Ala  Arg Arg Ala Gln Val  Pro Ser Ile 
    1055                 1060                 1065 

Lys Asp  Arg Ile Pro Tyr Val  Ile Val Ala Gln Thr  Arg Glu Val 
    1070                 1075                 1080 

Glu Glu  Thr Val Ala Arg Leu  Ala Ala Leu Arg Glu  Leu Asp Ala 
    1085                 1090                 1095 

Ala Ala  Pro Gly Asp Glu Pro  Ala Pro Pro Ala Ala  Leu Pro Ser 
    1100                 1105                 1110 

Pro Ala  Lys Arg Pro Arg Glu  Thr Pro Leu His Ala  Asp Pro Pro 
    1115                 1120                 1125 

Gly Gly  Ala Ser Lys Pro Arg  Lys Leu Leu Val Ser  Glu Leu Ala 
    1130                 1135                 1140 

Glu Asp  Pro Ala Tyr Ala Ile  Ala His Gly Val Ala  Leu Asn Thr 
    1145                 1150                 1155 

Asp Tyr  Tyr Phe Ser His Leu  Leu Gly Ala Ala Cys  Val Thr Phe 
    1160                 1165                 1170 

Lys Ala  Leu Phe Gly Asn Asn  Ala Lys Ile Thr Glu  Ser Leu Leu 
    1175                 1180                 1185 

Lys Arg  Phe Ile Pro Glu Val  Trp His Pro Pro Asp  Asp Val Ala 
    1190                 1195                 1200 

Ala Arg  Leu Arg Ala Ala Gly  Phe Gly Ala Val Gly  Ala Gly Ala 
    1205                 1210                 1215 

Thr Ala  Glu Glu Thr Arg Arg  Met Leu His Arg Ala  Phe Asp Thr 
    1220                 1225                 1230 

Leu Ala 
    1235