bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection of
Macaca nemestrina
from Disease following Pathogenic Simian Immunodeficiency Virus (SIV) Challenge: Utilization of SIV Nucleocapsid Mutant DNA Vaccines with and without an SIV Protein Boost
Authors: Gorelick Robert J. , Benveniste Raoul E. , Lifson Jeffrey D. , Yovandich Jason L. , Morton William R. , Kuller LaRene , Flynn Bernard M. , Fisher Bradley A. , Rossio Jeffrey L. , Piatak Michael , Bess Julian W. , Henderson Louis E. , Arthur Larry O. 
Published: July 2002

ABSTRACT

Molecular clones were constructed that express nucleocapsid (NC) deletion mutant simian immunodeficiency viruses (SIVs) that are replication defective but capable of completing virtually all of the steps of a single viral infection cycle. These steps include production of particles that are viral RNA deficient yet contain a full complement of processed viral proteins. The mutant particles are ultrastructurally indistinguishable from wild-type virus. Similar to a live attenuated vaccine, this approach should allow immunological presentation of a full range of viral epitopes, without the safety risks of replicating virus. A total of 11
Macaca nemestrina
macaques were inoculated with NC mutant SIV expressing DNA, intramuscularly (i.m.) in one study and i.m. and subcutaneously in another study. Six control animals received vector DNA lacking SIV sequences. Only modest and inconsistent humoral responses and no cellular immune responses were observed prior to challenge. Following intravenous challenge with 20 animal infectious doses of the pathogenic SIV(Mne) in a long-term study, all control animals became infected and three of four animals developed progressive SIV disease leading to death. All 11 NC mutant SIV DNA-immunized animals became infected following challenge but typically showed decreased initial peak plasma SIV RNA levels compared to those of control animals (
P
= 0.0007). In the long-term study, most of the immunized animals had low or undetectable postacute levels of plasma SIV RNA, and no CD4
+
T-cell depletion or clinical evidence of progressive disease, over more than 2 years of observation. Although a subset of immunized and control animals were boosted with SIV(Mne) proteins, no apparent protective benefit was observed. Immunization of macaques with DNA that codes for replication-defective but structurally complete virions appears to protect from or at least delay the onset of AIDS after infection with a pathogenic immunodeficiency virus. With further optimization, this may be a promising approach for vaccine development.
Immortalization of T Lymphocytes by Human T-Cell Leukemia Virus Type 1 Is Independent of the Tax-CBP/p300 Interaction
Authors: Robek Michael D. , Ratner Lee 
Published: July 2002

ABSTRACT

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein is a 40-kDa nuclear phosphoprotein which functions in the viral replication cycle as a transcriptional
trans
-activator of the viral long terminal repeat. Tax interacts with a variety of different transcription factors, including the CREB binding protein (CBP)/p300 family of transcriptional accessory proteins. We demonstrate that a Tax mutant defective for the CBP/p300 interaction retains the capacity to immortalize primary human T lymphocytes when it is expressed from a functional molecular clone of HTLV-1. Thus, immortalization of HTLV-1-infected cells appears to be independent of Tax-induced alterations in CBP/p300 function.
Inhibitory Effects of Nitric Oxide and Gamma Interferon on In Vitro and In Vivo Replication of Marek's Disease Virus
Authors: Xing Zheng , Schat Karel A. 
Published: July 2002

ABSTRACTThe replication of Marek's disease herpesvirus (MDV) and herpesvirus of turkeys (HVT) in chicken embryo fibroblast (CEF) cultures was inhibited by the addition ofS-nitroso-N-acetylpenicillamine, a nitric oxide (NO)-generating compound, in a dose-dependent manner. Treatment of CEF culture, prepared from 11-day-old embryos, with recombinant chicken gamma interferon (rChIFN-γ) and lipopolysaccharide (LPS) resulted in production of NO which was suppressed by the addition ofNG-monomethyll-arginine (NMMA), an inhibitor of inducible NO synthase (iNOS). Incubation of CEF cultures for 72 h prior to treatment with rChIFN-γ plus LPS was required for optimal NO production. Significant differences in NO production were observed in CEF derived from MDV-resistant N2a (major histocompatibility complex [MHC],B21B21) and MDV-susceptible S13(MHC,B13B13) and P2a (MHC,B19B19) chickens. N2a-derived CEF produced NO earlier and at higher levels than CEF from the other two lines. The lowest production of NO was detected in P2a-derived CEF. NO production in chicken splenocyte cultures followed a similar pattern, with the highest levels of NO produced in cultures from N2a chickens and the lowest levels produced in cultures from P2a chickens. Replication of MDV and HVT was significantly inhibited in CEF cultures treated with rChIFN-γ plus LPS and producing NO. The addition of NMMA to CEF treated with rChIFN-γ plus LPS reduced the inhibition. MDV infection of chickens treated withS-methylisothiourea, an inhibitor of iNOS, resulted in increased virus load compared to nontreated chickens. These results suggest that NO may play an important role in control of MDV replication in vivo.
Evidence for Viral Virulence as a Predominant Factor Limiting Human Immunodeficiency Virus Vaccine Efficacy
Authors: Mooij Petra , Bogers Willy M. J. M. , Oostermeijer Herman , Koornstra Wim , Ten Haaft Peter J. F. , Verstrepen Babs E. , Van Der Auwera Gert , Heeney Jonathan L. 
Published: July 2002

ABSTRACT

Current strategies in human immunodeficiency virus type 1 (HIV-1) vaccine development are often based on the production of different vaccine antigens according to particular genetic clades of HIV-1 variants. To determine if virus virulence or genetic distance had a greater impact on HIV-1 vaccine efficacy, we designed a series of heterologous chimeric simian/human immunodeficiency virus (SHIV) challenge experiments in HIV-1 subunit-vaccinated rhesus macaques. Of a total of 22 animals, 10 nonimmunized animals served as controls; the remainder were vaccinated with the CCR5 binding envelope of HIV-1
W6.1D
. In the first study, heterologous challenge included two nonpathogenic SHIV chimeras encoding the envelopes of the divergent clade B HIV-1
han2
and HIV-1
sf13
strains. In the second study, all immunized animals were rechallenged with SHIV
89.6p
, a virus closely related to the vaccine strain but highly virulent. Protection from either of the divergent SHIV
sf13
or SHIV
han2
challenges was demonstrated in the majority of the vaccinated animals. In contrast, upon challenge with the more related but virulent SHIV
89.6p
, protection was achieved in only one of the previously protected vaccinees. A secondary but beneficial effect of immunization on virus load and CD4
+
T-cell counts was observed despite failure to protect from infection. In addition to revealing different levels of protective immunity, these results suggest the importance of developing vaccine strategies capable of protecting from particularly virulent variants of HIV-1.
Enhancement of Adenovirus Vector Entry into CD70-Positive B-Cell Lines by Using a Bispecific CD70-Adenovirus Fiber Antibody
Authors: Israel Bruce F. , Pickles Ray J. , Segal David M. , Gerard Robert D. , Kenney Shannon C. 
Published: July 2002

ABSTRACTAlthough many recombinant adenovirus vectors (rAd) have been developed, especially by using group C adenoviruses, to transfer and express genes, such rAd do not readily infect B-cell lines due to the lack of the coxsackievirus-adenovirus receptor. Bispecific antibodies have been used in different cell systems to facilitate entry of rAd into otherwise nonpermissive cells. Bispecific antibody is synthesized by covalently linking two monoclonal antibodies with distinct specificities. It has been shown that lymphoproliferative tumors commonly express the cell surface protein CD70, while this receptor is normally expressed on only a small subset of highly activated B cells and T cells. We therefore investigated whether a bispecific antibody with specificities for the adenovirus fiber protein and CD70 can facilitate rAd entry and subsequent expression of rAd-encoded genes in CD70-positive B cells. We found high CD70 expression on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs), as well as some, but not all, Burkitt lymphoma (BL) lines. We show here that rAd encoding green fluorescent protein (Ad-GFP) infects EBV-transformed LCLs and a CD70-positive BL line 10- to 20-fold more efficiently in the presence of the CD70-fiber bispecific antibody. In contrast, the bispecific antibody does not enhance Ad-GFP infection in CD70-deficient BL cells. Using the CD70-fiber bispecific antibody, we increased the ability of rAd vectors encoding the EBV immediate-early proteins BZLF1 and BRLF1 to induce the lytic form of EBV infection in LCLs. These results indicate that the CD70-fiber bispecific antibody can enhance rAd infection of CD70-positive B cells and suggest the use of this vector to explore EBV-positive LCLs.
Cooperation of the V1/V2 and V3 Domains of Human Immunodeficiency Virus Type 1 gp120 for Interaction with the CXCR4 Receptor
Authors: Labrosse Béatrice , Treboute Carole , Brelot Anne , Alizon Marc 
Published: July 2002

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) entry is triggered by the interaction of the gp120 envelope glycoprotein with a cellular chemokine receptor, either CCR5 or CXCR4. We have identified different mutations in human CXCR4 that prevent efficient infection by one HIV-1 strain (NDK) but not another (LAI) and sought to define these strain-dependent effects at the gp120 level. The lack of activity toward the NDK strain of the HHRH chimeric CXCR4 in which the second extracellular loop (ECL2) derived from the rat CXCR4 and of CXCR4 with mutations at an aspartic acid in ECL2 (D193A and D193R) was apparently due to the sequence of the third variable loop (V3) of gp120, more precisely, to its C-terminal part. Indeed, substitution of the LAI V3 loop or only its C-terminal part in the NDK gp 120 context was sufficient to restore usage of the HHRH, D193A, and D193R receptors. The same result was achieved upon mutation of a single lysine residue of the NDK V3 loop to alanine (K319A) but not to arginine (K319R). These results provide a strong case for a direct interaction between the gp120 V3 loop and the ECL2 domain of CXCR4. By contrast, V3 substitutions had no effect on the inability of NDK to infect cells via a mutant CXCR4 in which the amino-terminal extracellular domain (NT) is deleted. In experiments with a set of chimeric NDK-LAI gp120s, the V1/V2 region from LAI gp120 was both necessary and sufficient for usage of the NT-deleted CXCR4. Different variable domains of gp120 can therefore cooperate for a functional interaction with CXCR4.
Immature Monocyte-Derived Dendritic Cells Are Productively Infected with Herpes Simplex Virus Type 1
Authors: Mikloska Zorka , Bosnjak Lidija , Cunningham Anthony L. 
Published: July 2002

ABSTRACTHerpes simplex viruses (HSV) have developed several immunoevasive strategies. Here we demonstrate a novel mechanism by which HSV type 1 may interfere with the immune response through infection of immature dendritic cells (DC) and selective downmodulation of costimulatory molecules. In our study we show productive infection of immature monocyte-derived DC, which closely resemble sessile Langerhans cells, by sequential expression of immediate-early, early, and late viral proteins and of glycoprotein D mRNA, as well as production of infectious virus of moderate titers. Infection was cytopathic, with the progressive loss of 20 to 45% of cells from 24 to 48 h after infection, with no more than 80% of DC found to be infected. These results are in contrast to those of previous findings of nonpermissive or abortive infection of monocytes and mature monocyte-derived DC. Infection of immature DC also led to selective and asynchronous downregulation of CD1a, CD40, CD54 (ICAM-1) (12 h postinfection), CD80 (24 h postinfection), and CD86 (48 h postinfection) but not of CD11c or major histocompatibility complex class I and II molecules when compared to DC exposed to UV-inactivated virus. Thus, we propose that productive infection of epidermal Langerhans cells in vivo may lead to delayed activation of T cells, allowing more time for replication of HSV type 1 in epidermal cells.
Target Cell Populations of Human Immunodeficiency Virus Type 1 in Peripheral Blood Lymphocytes with Different Chemokine Receptors at Various Stages of Disease Progression
Authors: Auewarakul Prasert , Sangsiriwut Kantima , Suwanagool Surapol , Wasi Chantapong 
Published: July 2002

ABSTRACT
We studied the distribution of human immunodeficiency virus type 1 (HIV-1) DNA in CCR5-positive and -negative peripheral blood lymphocyte populations in HIV-1-infected individuals. While HIV-1 DNA in the CCR5-positive population showed no correlation with CD4 count, the increase of total HIV-1 DNA with lower CD4 count was mainly contributed by the increase of HIV-1 DNA in the CCR5-negative population. This might indicate the change in coreceptor usage from CCR5 to CXCR4 in later stages of disease progression. However, some of the samples with a high viral DNA load in the CCR5-negative population did not have any characteristic of the V3 loop sequence that is compatible with CXCR4 usage or the syncytium-inducing (SI) phenotype. We also did not find any known characteristic change predictive of the SI phenotype in V1 and V2 sequences. Our findings showed that there might be a shift in target cell populations during disease progression, and this shift was not necessarily associated with the genetic changes characteristic of CXCR4 usage.
Effects of DNA Structure and Homology Length on Vaccinia Virus Recombination
Authors: Yao Xiao-Dan , Evans David H. 
Published: July 2002

ABSTRACT
Replicating poxviruses catalyze high-frequency recombination reactions by a process that is not well understood. Using transfected DNA substrates we show that these viruses probably use a single-strand annealing recombination mechanism. Plasmids carrying overlapping portions of a luciferase gene expression cassette and luciferase assays were first shown to provide an accurate method of assaying recombinant frequencies. We then transfected pairs of DNAs into virus-infected cells and monitored the efficiencies of linear-by-linear, linear-by-circle, and circle-by-circle recombination. These experiments showed that vaccinia virus recombination systems preferentially catalyze linear-by-linear reactions much more efficiently than circle-by-circle reactions and catalyze circle-by-circle reactions more efficiently than linear-by-circle reactions. Reactions involving linear substrates required surprisingly little sequence identity, with only 16-bp overlaps still permitting ∼4% recombinant production. Masking the homologies by adding unrelated DNA sequences to the ends of linear substrates inhibited recombination in a manner dependent upon the number of added sequences. Circular molecules were also recombined by replicating viruses but at frequencies 15- to 50-fold lower than are linear substrates. These results are consistent with mechanisms in which exonuclease or helicase processing of DNA ends permits the forming of recombinants through annealing of complementary single strands. Our data are not consistent with a model involving strand invasion reactions, because such reactions should favor mixtures of linear and circular substrates. We also noted that many of the reaction features seen in vivo were reproduced in a simple in vitro reaction requiring only purified vaccinia virus DNA polymerase, single-strand DNA binding protein, and pairs of linear substrates. The 3′-to-5′ exonuclease activity of poxviral DNA polymerases potentially catalyzes recombination in vivo.
Influenza Virus NS1 Protein Induces Apoptosis in Cultured Cells
Authors: Schultz-Cherry Stacey , Dybdahl-Sissoko Naomi , Neumann Gabriele , Kawaoka Yoshihiro , Hinshaw Virginia S. 
Published: July 2002

ABSTRACTThe importance of influenza viruses as worldwide pathogens in humans, domestic animals, and poultry is well recognized. Discerning how influenza viruses interact with the host at a cellular level is crucial for a better understanding of viral pathogenesis. Influenza viruses induce apoptosis through mechanisms involving the interplay of cellular and viral factors that may depend on the cell type. However, it is unclear which viral genes induce apoptosis. In these studies, we show that the expression of the nonstructural (NS) gene of influenza A virus is sufficient to induce apoptosis in MDCK and HeLa cells. Further studies showed that the multimerization domain of the NS1 protein but not the effector domain is required for apoptosis. However, this mutation is not sufficient to inhibit apoptosis using whole virus.
Tick-Borne Langat/Mosquito-Borne Dengue Flavivirus Chimera, a Candidate Live Attenuated Vaccine for Protection against Disease Caused by Members of the Tick-Borne Encephalitis Virus Complex: Evaluation in Rhesus Monkeys and in Mosquitoes
Authors: Pletnev Alexander G. , Bray Michael , Hanley Kathryn A. , Speicher Jim , Elkins Randy 
Published: July 2002

ABSTRACT

Langat virus (LGT), strain TP21, a naturally avirulent tick-borne flavivirus, was used to construct a chimeric candidate virus vaccine which contained LGT genes for premembrane (preM) and envelope (E) glycoprotein and all other sequences derived from dengue type 4 virus (DEN4). The live virus vaccine was developed to provide resistance to the highly virulent, closely related tick-borne flaviviruses that share protective E epitopes among themselves and with LGT. Toward that end the chimera, initially recovered in mosquito cells, was adapted to grow to high titer in qualified simian Vero cells. When inoculated intraperitoneally (i.p.), the Vero cell-adapted LGT TP21/DEN4 chimera remained completely attenuated for SCID mice. Significantly, the chimera protected immunocompetent mice against the most virulent tick-borne encephalitis virus (TBEV). Subsequently, rhesus monkeys were immunized in groups of 4 with 10
5
or 10
7
PFU of LGT strain TP21, with 10
5
PFU of DEN4, or with 10
3
, 10
5
, or 10
7
PFU of the chimera. Each of the monkeys inoculated with DEN4 or LGT TP21 became viremic, and the duration of viremia ranged from 1 to 5 days. In contrast, viremia was detected in only 1 of 12 monkeys inoculated with the LGT TP21/DEN4 chimera; in this instance the level of viremia was at the limit of detection. All monkeys immunized with the chimera or LGT TP21 virus developed a moderate to high level of neutralizing antibodies against LGT TP21 as well as TBEV and were completely protected against subsequent LGT TP21 challenge, whereas monkeys previously immunized with DEN4 virus became viremic when challenged with LGT TP21. These observations suggest that the chimera is attenuated, immunogenic, and able to induce a protective immune response. Furthermore, passive transfer of serum from monkeys immunized with chimera conferred significant protection to mice subsequently challenged with 100 i.p. 50% lethal doses of the highly virulent TBEV. The issue of transmissibility of the chimera by mosquitoes was addressed by inoculating a nonhematophagous mosquito,
Toxorhynchites splendens
, intrathoracically with the chimera or its DEN4 or LGT parent. Neither the LGT TP21/DEN4 vaccine candidate nor the wild-type LGT TP21 virus was able to infect this mosquito species, which is highly permissive for dengue viruses. Certain properties of the chimera, notably its attenuation for monkeys, its immunogenicity, and its failure to infect a highly permissive mosquito host, make it a promising vaccine candidate for use in immunization against severe disease caused by many tick-borne flaviviruses.
Characterization of a Novel Simian Immunodeficiency Virus from Guereza Colobus Monkeys (
Colobus guereza
) in Cameroon: a New Lineage in the Nonhuman Primate Lentivirus Family
Authors: Courgnaud Valérie , Pourrut Xavier , Bibollet-Ruche Frédéric , Mpoudi-Ngole Eitel , Bourgeois Anke , Delaporte Eric , Peeters Martine 
Published: July 2002

ABSTRACT

Exploration of the diversity among primate lentiviruses is necessary to elucidate the origins and evolution of immunodeficiency viruses. During a serological survey in Cameroon, we screened 25 wild-born guereza colobus monkeys (
Colobus guereza
) and identified 7 with HIV/SIV cross-reactive antibodies. In this study, we describe a novel lentivirus, named SIVcol, prevalent in guereza colobus monkeys. Genetic analysis revealed that SIVcol was very distinct from all other known SIV/HIV isolates, with average amino acid identities of 40% for Gag, 50% for Pol, 28% for Env, and around 25% for proteins encoded by five other genes. Phylogenetic analyses confirmed that SIVcol is genetically distinct from other previously characterized primate lentiviruses and clusters independently, forming a novel lineage, the sixth in the current classification.
Cercopithecidae
monkeys (Old World monkeys) are subdivided into two subfamilies, the
Colobinae
and the
Cercopithecinae
, and, so far, all
Cercopithecidae
monkeys from which lentiviruses have been isolated belong to the
Cercopithecinae
subfamily. Therefore, SIVcol from guereza colobus monkeys (
C. guereza
) is the first primate lentivirus identified in the
Colobinae
subfamily and the divergence of SIVcol may reflect divergence of the host lineage.
Engraftment of NOD/SCID Mice with Human CD34+Cells Transduced by Concentrated Oncoretroviral Vector Particles Pseudotyped with the Feline Endogenous Retrovirus (RD114) Envelope Protein
Authors: Gatlin Joel , Melkus Michael W. , Padgett Angela , Kelly Patrick F. , Garcia J. Victor 
Published: July 2002

ABSTRACTOncoretrovirus vectors pseudotyped with the feline endogenous retrovirus (RD114) envelope protein produced by the FLYRD18 packaging cell line have previously been shown to transduce human hematopoietic progenitor cells with a greater efficiency than similar amphotropic envelope-pseudotyped vectors. In this report, we describe the production and efficient concentration of RD114-pseudotyped murine leukemia virus (MLV)-based vectors. Following a single round of centrifugation, vector supernatants were concentrated approximately 200-fold with a 50 to 70% yield. Concentrated vector stocks transduced prestimulated human CD34+(hCD34+) cells with approximately 69% efficiency (n= 7, standard deviation = 4.4%) using a single addition of vector at a low multiplicity of infection (MOI = 5). Introduction of transduced hCD34+cells into irradiated NOD/SCID recipients resulted in multilineage engraftment with long-term transgene expression. These data demonstrate that RD114-pseudotyped MLV-based vectors can be efficiently concentrated to high titers and that hCD34+cells transduced with concentrated vector stocks retain in vivo repopulating potential. These results highlight the potential of RD114-pseudotyped oncoretrovirus vectors for future clinical implementation in hematopoietic stem cell gene transfer.