bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Anti-CXCL10 Monoclonal Antibody on Herpes Simplex Virus Type 1 Keratitis and Retinal Infection
Authors: Carr Daniel J. J. , Chodosh James , Ash John , Lane Thomas E. 
Published: August 2003

ABSTRACTThe inflammatory response to acute ocular herpes simplex virus type 1 (HSV-1) infection in mice involves the innate and adaptive immune response, with an associated increase in the secretion of chemokines, including CXCL10 (interferon-inducible protein 10 kDa [IP-10]). Neutralizing antibodies to mouse CXCL10 were used to determine the role of CXCL10 during the acute phase of HSV-1 ocular infection. Treatment of HSV-1-infected mice with antibody to CXCL10 significantly reduced CXCL10 levels in the eye and trigeminal ganglion and reduced mononuclear cell infiltration into the corneal stroma. These results coincided with reduced ICAM-1 and CXCR3 transcript expression, macrophage inflammatory protein-1α and CXCL10 levels, and corneal pathology but increased viral titers in the stroma and trigeminal ganglion. Progression of the virus from the corneal stroma to the retina during acute infection was significantly hindered in anti-CXCL10-treated mice. In addition, colocalization of viral antigen with infiltrating leukocytes in the iris and retina during acute infection suggests that one means by which HSV-1 traffics to the retina involves inflammatory cells (primarily CD11b+cells). Collectively, the results suggest that CXCL10 expression in the eye initially orchestrates the inflammatory response to acute HSV-1 infection, which facilitates the spread of the virus to other restricted sites within the eye.
Distinct Cycling CD4+- and CD8+-T-Cell Profiles during the Asymptomatic Phase of Simian Immunodeficiency Virus SIVmac251 Infection in Rhesus Macaques
Authors: Monceaux V. , Fang R. Ho Tsong , Cumont M. C. , Hurtrel B. , Estaquier J. 
Published: August 2003

ABSTRACTElevated CD4 T-cell turnover may lead to the exhaustion of the immune system during human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) infections. However, this hypothesis remains controversial. Most studies of this subject have concerned the blood, and information about the lymph nodes is rare and controversial. We used Ki67 expression to measure cycling T cells in the blood and lymph nodes of uninfected macaques and of macaques infected with a pathogenic SIVmac251 strain or with a nonpathogenic SIVmac251Δnef clone. During the asymptomatic phase of infection, the number of cycling CD8+T cells progressively increased (two- to eightfold) both in the blood and in the lymph nodes of macaques infected with SIVmac251. This increase was correlated with viral replication and the progression to AIDS. In contrast, no increases in the numbers of cycling CD4+T cells were found in the blood or lymph nodes of macaques infected with the pathogenic SIVmac251 strain in comparison with SIVmac251Δnef-infected or healthy macaques during this chronic phase. However, the lymph nodes of pre-AIDS stage SIVmac251-infected macaques contained more cycling CD4+T cells (low baseline CD4+-T-cell counts in the blood). Taken together, these results show that the profiles of CD4+- and CD8+-T-cell dynamics are distinct both in the lymph nodes and blood and suggest that higher CD4+-T-cell proliferation at the onset of AIDS may lead to the exhaustion of the immune system.
T Cells Cause Acute Immunopathology and Are Required for Long-Term Survival in Mouse Adenovirus Type 1-Induced Encephalomyelitis
Authors: Moore Martin L. , Brown Corrie C. , Spindler Katherine R. 
Published: August 2003

ABSTRACTInfection of adult C57BL/6 (B6) mice with mouse adenovirus type 1 (MAV-1) results in dose-dependent encephalomyelitis. Utilizing immunodeficient mice, we analyzed the roles of T cells, T-cell subsets, and T-cell-related functions in MAV-1-induced encephalomyelitis. T cells, major histocompatibility complex (MHC) class I, and perforin contributed to acute disease signs at 8 days postinfection (p.i.). Acute MAV-1-induced encephalomyelitis was absent in mice lacking T cells and in mice lacking perforin. Mice lacking α/β T cells had higher levels of infectious MAV-1 at 8 days, 21 days, and 12 weeks p.i., and these mice succumbed to MAV-1-induced encephalomyelitis at 9 to 16 weeks p.i. Thus, α/β T cells were required for clearance of MAV-1. MAV-1 was cleared in mice lacking perforin, MHC class I or II, CD4+T cells, or CD8+T cells. Our results are consistent with a model in which either CD8+or CD4+T cells are sufficient for clearance of MAV-1. Furthermore, perforin contributed to MAV-1 disease but not viral clearance. We have established two critical roles for T cells in MAV-1-induced encephalomyelitis. T cells caused acute immunopathology and were required for long-term host survival of MAV-1 infection.
Heparan Sulfates and Coxsackievirus-Adenovirus Receptor: Each One Mediates Coxsackievirus B3 PD Infection
Authors: Zautner A. E. , Körner U. , Henke A. , Badorff C. , Schmidtke M. 
Published: August 2003

ABSTRACT

Amino acid exchanges in the virus capsid protein VP1 allow the coxsackievirus B3 variant PD (CVB3 PD) to replicate in decay accelerating factor (DAF)-negative and coxsackievirus-adenovirus receptor (CAR)-negative cells. This suggests that molecules other than DAF and CAR are involved in attachment of this CVB3 variant to cell surfaces. The observation that productive infection associated with cytopathic effect occurred in Chinese hamster ovary (CHO-K1) cells, whereas heparinase-treated CHO-K1 cells, glucosaminoglycan-negative pgsA-745, heparan sulfate (HS)-negative pgsD-677, and pgsE-606 cells with significantly reduced N-sulfate expression resist CVB3 PD infection, indicates a critical role of highly sulfated HS. 2-
O
-sulfate-lacking pgsF-17 cells represented the cell line with minimum HS modifications susceptible for CVB3 PD. Inhibition of virus replication in CHO-K1 cells by polycationic compounds, pentosan polysulfate, lung heparin, and several intestinal but not kidney HS supported the hypothesis that CVB3 PD uses specific modified HS for entry. In addition, recombinant human hepatocyte growth factor blocked CVB3 PD infection. However, CAR also mediates CVB3 PD infection, because this CVB3 variant replicates in HS-lacking but CAR-bearing Raji cells, infection could be prevented by pretreatment of cells with CAR antibody, and HS-negative pgsD-677 cells transfected with CAR became susceptible for CVB3 PD. These results demonstrate that the amino acid substitutions in the viral capsid protein VP1 enable CVB3 PD to use specific modified HS as an entry receptor in addition to CAR.
Enhanced Mucosal Immunoglobulin A Response of Intranasal Adenoviral Vector Human Immunodeficiency Virus Vaccine and Localization in the Central Nervous System
Authors: Lemiale Franck , Kong Wing-pui , Akyürek Levent M. , Ling Xu , Huang Yue , Chakrabarti Bimal K. , Eckhaus Michael , Nabel Gary J. 
Published: August 2003

ABSTRACTReplication-defective adenovirus (ADV) vectors represent a promising potential platform for the development of a vaccine for AIDS. Although this vector is typically administered intramuscularly, it would be desirable to induce mucosal immunity by delivery through alternative routes. In this study, the immune response and biodistribution of ADV vectors delivered by different routes were evaluated. ADV vectors expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pol, and Env were delivered intramuscularly or intranasally into mice. Intranasal immunization induced greater HIV-specific immunoglobulin A (IgA) responses in mucosal secretions and sera than in animals with intramuscular injection, which showed stronger systemic cellular and IgG responses. Administration of the vaccine through an intranasal route failed to overcome prior ADV immunity. Animals exposed to ADV prior to vaccination displayed substantially reduced cellular and humoral immune responses to HIV antigens in both groups, though the reduction was greater in animals immunized intranasally. This inhibition was partially overcome by priming with a DNA expression vector expressing HIV-1 Gag, Pol, and Env before boosting with the viral vector. Biodistribution of recombinant adenovirus (rADV) vectors administered intranasally revealed infection of the central nervous system, specifically in the olfactory bulb, possibly via retrograde transport by olfactory neurons in the nasal epithelium, which may limit the utility of this route of delivery of ADV vector-based vaccines.
Restriction of Amino Acid Change in Influenza A Virus H3HA: Comparison of Amino Acid Changes Observed in Nature and In Vitro
Authors: Nakajima Katsuhisa , Nobusawa Eri , Tonegawa Ken , Nakajima Setsuko 
Published: August 2003

ABSTRACT
We introduced 248 single-point amino acid changes into hemagglutinin (HA) protein of the A/Aichi/2/68 (H3N2) strain by a PCR random mutation method. These changes were classified as positive or negative according to their effect on hemadsorption activity. We observed following results. (i) The percentage of surviving amino acid changes on the HA1 domain that did not abrogate hemadsorption activity was calculated to be ca. 44%. In nature, it is estimated to be ca. 39.6%. This difference in surviving amino acid changes on the HA protein between natural isolates and in vitro mutants might be due to the immune pressure against the former. (ii) A total of 26 amino acid changes in the in vitro mutants matched those at which mainstream amino acid changes had occurred in the H3HA1 polypeptide from 1968 to 2000. Of these, 25 were positive. We suggest that the majority of amino acid changes on the HA protein during evolution might be restricted to those that were positive on the HA of A/Aichi/2/68. (iii) We constructed two-point amino acid changes on the HA protein by using positive mutants. These two-point amino acid changes with a random combination did not inhibit hemadsorption activity. It is possible that an accumulation of amino acid change might occur without order. (iv) From the analysis of amino acids participating in mainstream amino acid change, each antigenic site could be further divided into smaller sites. The amino acid substitutions in the gaps between these smaller sites resulted in mostly hemadsorption-negative changes. These gap positions may play an important role in maintaining the function of the HA protein, and therefore amino acid changes are restricted at these locations.
Combinations of Two Capsid Regions Controlling Canine Host Range Determine Canine Transferrin Receptor Binding by Canine and Feline Parvoviruses
Authors: Hueffer Karsten , Govindasamy Lakshman , Agbandje-McKenna Mavis , Parrish Colin R. 
Published: August 2003

ABSTRACT
Feline panleukopenia virus (FPV) and its host range variant, canine parvovirus (CPV), can bind the feline transferrin receptor (TfR), while only CPV binds to the canine TfR. Introducing two CPV-specific changes into FPV (at VP2 residues 93 and 323) endowed that virus with the canine TfR binding property and allowed canine cell infection, although neither change alone altered either property. In CPV the reciprocal changes of VP2 residue 93 or 323 to the FPV sequences individually resulted in modest reductions in infectivity for canine cells. Changing both residues in CPV to the FPV amino acids blocked the canine cell infection, but that virus was still able to bind the canine TfR at low levels. This shows that both CPV-specific changes control canine TfR binding but that binding is not always sufficient to mediate infection.
Development of Pseudorabies Virus Strains Expressing Red Fluorescent Proteins: New Tools for Multisynaptic Labeling Applications
Authors: Banfield Bruce W. , Kaufman Jessica D. , Randall Jessica A. , Pickard Gary E. 
Published: August 2003

ABSTRACT
The transsynaptic retrograde transport of the pseudorabies virus Bartha (PRV-Bartha) strain has become an important neuroanatomical tract-tracing technique. Recently, dual viral transneuronal labeling has been introduced by employing recombinant strains of PRV-Bartha engineered to express different reporter proteins. Dual viral transsynaptic tracing has the potential of becoming an extremely powerful method for defining connections of single neurons to multiple neural circuits in the brain. However, the present use of recombinant strains of PRV expressing different reporters that are driven by different promoters, inserted in different regions of the viral genome, and detected by different methods limits the potential of these recombinant virus strains as useful reagents. We previously constructed and characterized PRV152, a PRV-Bartha derivative that expresses the enhanced green fluorescent protein. The development of a strain isogenic to PRV152 and differing only in the fluorescent reporter would have great utility for dual transsynaptic tracing. In this report, we describe the construction, characterization, and application of strain PRV614, a PRV-Bartha derivative expressing a novel monomeric red fluorescent protein, mRFP1. In contrast to viruses expressing DsRed and DsRed2, PRV614 displayed robust fluorescence both in cell culture and in vivo following transsynaptic transport through autonomic circuits afferent to the eye. Transneuronal retrograde dual PRV labeling has the potential to be a powerful addition to the neuroanatomical tools for investigation of neuronal circuits; the use of strain PRV614 in combination with strain PRV152 will eliminate many of the pitfalls associated with the presently used pairs of PRV recombinants.
Magnitude and Diversity of Cytotoxic-T-Lymphocyte Responses Elicited by Multiepitope DNA Vaccination in Rhesus Monkeys
Authors: Subbramanian Ramu A. , Kuroda Marcelo J. , Charini William A. , Barouch Dan H. , Costantino Cristina , Santra Sampa , Schmitz Jörn E. , Martin Kristi L. , Lifton Michelle A. , Gorgone Darci A. , Shiver John W. , Letvin Norman L. 
Published: August 2003

ABSTRACTIn an effort to develop an AIDS vaccine that elicits high-frequency cytotoxic-T-lymphocyte (CTL) responses with specificity for a diversity of viral epitopes, we explored two prototype multiepitope plasmid DNA vaccines in the simian-human immunodeficiency virus/rhesus monkey model to determine their efficiency in priming for such immune responses. While a simple multiepitope vaccine construct demonstrated limited immunogenicity in monkeys, this same multiepitope genetic sequence inserted into an immunogenic simian immunodeficiency virusgagDNA vaccine elicited high-frequency CTL responses specific for all of the epitopes included in the vaccine. Both multiepitope vaccine prototypes primed for robust epitope-specific CTL responses that developed following boosting with recombinant modified vaccinia virus Ankara vaccines expressing complete viral proteins. The natural hierarchy of immunodominance for these epitopes was clearly evident in the boosted monkeys. These studies suggest that multiepitope plasmid DNA vaccine-based prime-boost regimens can efficiently prime for CTL responses of increased breadth and magnitude, although they do not overcome predicted hierarchies of immunodominance.
Analysis of Early Human Immunodeficiency Virus Type 1 DNA Synthesis by Use of a New Sensitive Assay for Quantifying Integrated Provirus
Authors: Brussel Audrey , Sonigo Pierre 
Published: August 2003

ABSTRACT

A novel
Alu
-long terminal repeat (LTR)-based real-time nested-PCR assay was developed to quantify integrated human immunodeficiency virus type 1 (HIV-1) DNA in infected cells with both accuracy and high sensitivity (six proviruses within 50,000 cell equivalents). Parallel assays for total HIV-1 DNA and two-LTR HIV-1 DNA circles allowed the synthesis and fate of the different HIV-1 DNA species to be monitored upon a single round of viral replication.
Murine Cytomegalovirus Infection Inhibits Tumor Necrosis Factor Alpha Responses in Primary Macrophages
Authors: Popkin Daniel L. , Virgin Herbert W. 
Published: August 2003

ABSTRACTDespite robust host immune responses the betaherpesvirus murine cytomegalovirus (MCMV) is able to establish lifelong infection. This capacity is due at least in part to the virus utilizing multiple immune evasion mechanisms to blunt host responses. Macrophages are an important cell for MCMV infection, dissemination, and latency despite expression in the host of multiple cytokines, including tumor necrosis factor alpha (TNF-α), that can induce an antiviral state in macrophages or other cells. In this study, we found that MCMV infection of bone marrow-derived macrophages inhibited TNF-α-induced ICAM-1 surface expression and mRNA expression in infected cells via expression of immediate early and/or early viral genes. MCMV infection blocked TNF-α-induced nuclear translocation of NF-κB. This inhibition of TNF-α signaling was explained by a decrease in TNF receptor 1 (TNFR1) and TNFR2 that was due to decreased mRNA for the latter. These findings provide a mechanism by which MCMV can evade the effects of an important host cytokine in macrophages.
Hepatitis C Virus-Like Particle Budding: Role of the Core Protein and Importance of Its Asp
111
Authors: Blanchard Emmanuelle , Hourioux Christophe , Brand Denys , Ait-Goughoulte Malika , Moreau Alain , Trassard Sylvie , Sizaret Pierre-Yves , Dubois Frederic , Roingeard Philippe 
Published: August 2003

ABSTRACT
In the absence of a hepatitis C virus (HCV) culture system, the use of a Semliki Forest virus replicon expressing genes encoding HCV structural proteins that assemble into HCV-like particles provides an opportunity to study HCV morphogenesis. Using this system, we showed that the HCV core protein constitutes the budding apparatus of the virus and that its targeting to the endoplasmic reticulum by means of the signal sequence of E1 protein is essential for budding. In addition, the aspartic acid at position 111 in the HCV core protein sequence was found to be crucial for virus assembly, demonstrating the usefulness of this system for mapping amino acids critical to HCV morphogenesis.
Genetic Variability of Immunomodulatory Genes in Ectromelia Virus Isolates Detected by Denaturing High-Performance Liquid Chromatography
Authors: Ribas Gloria , Rivera Jose , Saraiva Margarida , Campbell R. Duncan , Alcami Antonio 
Published: August 2003

ABSTRACTThe genetic variability of nine genes in 12 isolates and strains of ectromelia virus, which causes a smallpox-like disease (mousepox) in mice, was determined and allows for classification of ectromelia viruses. The low genetic variability suggests that evolutionary pressure maintains the activity of immunomodulatory genes in natural poxvirus infections.
3′ to 5′ Exonuclease Activity of Herpes Simplex Virus Type 1 DNA Polymerase Modulates Its Strand Displacement Activity
Authors: Zhu Yali , Trego Kelly S. , Song Liping , Parris Deborah S. 
Published: August 2003

ABSTRACT

Using a minicircle DNA primer-template, the wild-type catalytic subunit of herpes simplex virus type 1 (HSV-1) DNA polymerase (pol) was shown to lack significant strand displacement activity with or without its processivity factor, UL42. However, an exonuclease-deficient (exo
−
) pol (D368A) was capable of slow strand displacement. Although UL42 increased the rate (2/s) and processivity of strand displacement by exo
−
pol, the rate was slower than that for gap-filling synthesis. High inherent excision rates on matched primer-templates and rapid idling-turnover (successive rounds of excision and polymerization) of exo-proficient polymerases correlated with poor strand displacement activity. The results suggest that the exo activity of HSV-1 pol modulates its ability to engage in strand displacement, a function that may be important to the viability and genome stability of the virus.
Dephosphorylation of eIF-2α Mediated by the γ
1
34.5 Protein of Herpes Simplex Virus Type 1 Is Required for Viral Response to Interferon but Is Not Sufficient for Efficient Viral Replication
Authors: Cheng Guofeng , Yang Kui , He Bin 
Published: August 2003

ABSTRACT

The γ
1
34.5 protein of herpes simplex virus type 1 (HSV-1) functions to block the shutoff of protein synthesis involving double-stranded RNA-dependent protein kinase (PKR). In this process, the γ
1
34.5 protein recruits cellular protein phosphatase 1 (PP1) to form a high-molecular-weight complex that dephosphorylates eIF-2α. Here we show that the γ
1
34.5 protein is capable of mediating eIF-2α dephosphorylation without any other viral proteins. While deletion of amino acids 1 to 52 from the γ
1
34.5 protein has no effect on eIF-2α dephosphorylation, further truncations up to amino acid 146 dramatically reduce the activity of the γ
1
34.5 protein. An additional truncation up to amino acid 188 is deleterious, indicating that the carboxyl-terminal domain alone is not functional. Like wild-type HSV-1, the γ
1
34.5 mutant with a truncation of amino acids 1 to 52 is resistant to interferon, and resistance to interferon is coupled to eIF-2α dephosphorylation. Intriguingly, this mutant exhibits a similar growth defect seen for the γ
1
34.5 null mutant in infected cells. Restoration of the wild-type γ
1
34.5 gene in the recombinant completely reverses the phenotype. These results indicate that eIF-2α dephosphorylation mediated by the γ
1
34.5 protein is required for HSV response to interferon but is not sufficient for viral replication. Additional functions or activities of the γ
1
34.5 protein contribute to efficient viral infection.
Identification of White Spot Syndrome Virus Latency-Related Genes in Specific-Pathogen-Free Shrimps by Use of a Microarray
Authors: Khadijah Siti , Neo Soek Ying , Hossain M. S. , Miller Lance D. , Mathavan S. , Kwang Jimmy 
Published: August 2003

ABSTRACT
To investigate whether specific-pathogen-free (SPF) shrimps are asymptomatic carriers of white spot syndrome virus (WSSV), we used a WSSV-specific DNA microarray to measure WSSV gene expression in SPF and WSSV-infected shrimps. Three WSSV genes were found to be relatively highly expressed in SPF shrimps. Reverse transcription-PCR using nested primers as well as real-time detection confirmed that these genes have no detectable counterparts in GenBank; structural analysis of the putative proteins revealed helix-loop-helix and leucine zipper motifs. Viral sequences could be PCR amplified from genomic DNA of SPF shrimp, further supporting the suggestion that these shrimps are asymptomatic carriers.
Interleukin-15 and Natural Killer and NKT Cells Play a Critical Role in Innate Protection against Genital Herpes Simplex Virus Type 2 Infection
Authors: Ashkar Ali A. , Rosenthal Kenneth L. 
Published: August 2003

ABSTRACTInterleukin-15 (IL-15), natural killer (NK) cells, and NK T (NKT) cells, components of the innate immune system, are known to contribute to defense against pathogens, including viruses. Here we report that IL-15−/−(NK−and NKT−/+) mice and RAG-2−/−/γc−/−(NK−and NKT−) mice that lack all lymphoid cells were very susceptible to vaginal infection with a low dose of herpes simplex virus type 2 (HSV-2). IL-15−/−and RAG-2−/−/γc−/−mice were 100-fold more susceptible and RAG-2−/−, CD-1−/−(NKT−), and gamma interferon (IFN-γ)−/−mice were 10-fold more susceptible to vaginal HSV-2 infection than control C57BL/6 mice. NK and/or NKT cells were the early source of IFN-γ in vaginal secretions following genital HSV-2 infection. This study demonstrates that IL-15 and NK-NKT cells are critical for innate protection against genital HSV-2.
Parameters Driving the Selection of Nelfinavir-Resistant Human Immunodeficiency Virus Type 1 Variants
Authors: Perrin Virginie , Mammano Fabrizio 
Published: August 2003

ABSTRACT
We investigated the parameters driving nelfinavir resistance, along the D30N and L90M evolutionary pathways. The advantage of the D30N mutant was mostly due to its resistance level, while the L90M mutation allowed preservation of infectivity coupled with minimal resistance. Emergence of secondary mutations further increased the selective advantage of viruses harboring D30N.