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pathogenicity of live, attenuated siv after mucosal infection of neonatal macaques.adult macaques do not develop disease after infection with a nef deletion mutant of the simian immunodeficiency virus (siv) and are protected against challenge with pathogenic virus. this finding led to the proposal to use nef-deleted viruses as live, attenuated vaccines to prevent human acquired immunodeficiency syndrome (aids). in contrast, neonatal macaques developed persistently high levels of viremia after oral exposure to and siv nef, vpr, and negative regulatory element (nre) deletion mut ...19957892606
antibodies to the putative siv infection-enhancing domain diminish beneficial effects of an siv gp160 vaccine in rhesus macaques.to demonstrate that antibodies against amino acids (aa) 603-622 of the siv gp41 transmembrane glycoprotein enhance infection of siv in vivo.19957893438
bone marrow monocyte/macrophages are an early cellular target of pathogenic and nonpathogenic isolates of simian immunodeficiency virus (sivmac) in rhesus macaques.hematopoietic abnormalities are a common complication of human immunodeficiency virus infection in humans. however, the pathogenesis of these abnormalities remains unclear. simian immunodeficiency virus (siv) infection of rhesus macaques is a well-recognized animal model for acquired immunodeficiency syndrome. our previous studies have determined that in early siv infection, rhesus macaques develop peripheral blood and bone marrow pathologic changes within the first 14 days after intravenous ino ...19957898051
characterization of nef sequences in long-term survivors of human immunodeficiency virus type 1 infection.studies with the simian immunodeficiency virus have shown that nef deletion results in a low level of viremia and a lack of disease progression in monkeys. given the similarity of this clinical profile to that observed in long-term survivors of human immunodeficiency virus type 1 (hiv-1) infection, we sought to examine the nef gene in 10 patients who are clinically healthy and immunologically normal despite 12 to 15 years of infection. pcr and dna sequencing were used to determine nef sequences ...19957983771
identification of rantes, mip-1 alpha, and mip-1 beta as the major hiv-suppressive factors produced by cd8+ t cells.evidence suggests that cd8+ t lymphocytes are involved in the control of human immunodeficiency virus (hiv) infection in vivo, either by cytolytic mechanisms or by the release of hiv-suppressive factors (hiv-sf). the chemokines rantes, mip-1 alpha, and mip-1 beta were identified as the major hiv-sf produced by cd8+ t cells. two active proteins purified from the culture supernatant of an immortalized cd8+ t cell clone revealed sequence identity with human rantes and mip-1 alpha. rantes, mip-1 alp ...19958525373
assembly of siv virus-like particles containing envelope proteins using a baculovirus expression system.the requirements for siv particle assembly and envelope incorporation were investigated using a baculovirus expression system. the pr56gag precursor protein expressed under control of the polyhedrin promoter (ppolh) produced high levels of immature retrovirus-like particles (vlp) upon expression in sf9 insect cells. to determine the optimal conditions for envelope protein (env) incorporation into vlp, two recombinant baculoviruses expressing the siv envelope protein under control of a very late ...19958525638
morpho-functional changes of follicular dendritic cells (fdc) and lymph node structure in simian immunodeficiency virus (siv) infection. 19958526085
generation of diversity in the hierarchy of t-cell epitope responses following different routes of immunization with simian immunodeficiency virus protein.to examine whether the route of immunization determines the hierarchy of t-cell epitope proliferative responses in macaques.19958527073
obtaining marketing authorization for nucleic acid vaccines in the european union.nucleic acid vaccines are promising candidates for easy-to-handle and cost-effective vaccines that combine the safety of subunit vaccines with the efficacy of live virus vaccines. in order to obtain marketing authorization for a nucleic acid vaccine in all member states of the european union, a single application dossier has to be filed with the european agency for the evaluation of medicinal products. notes for guidance on the data necessary to support applications are available. the preclinica ...19958546391
simian immunodeficiency virus dna vaccine trial in macaques. 19958546394
amino acid sequence requirements for the incorporation of the vpx protein of simian immunodeficiency virus into virion particles.to investigate the amino acid sequence determinants for the incorporation of vpx protein into virion particles, several mutations were introduced into the vpx gene of sivmac239 proviral dna, and the effects of mutations on the expression and assembly of the vpx protein were studied. the results show that deletions of amino acids from 78 to 80 or from 82 to 87 abolished the incorporation of the expressed vpx protein into virion particles. other vpx mutants, including a full-length vpx-vpr fusion ...19958548329
analysis and localization of cyclophilin a found in the virions of human immunodeficiency virus type 1 mn strain.previous reports have shown that cyclophilin a (cypa) is found to be specifically associated with human immunodeficiency virus type-1 (hiv-1) virions and is required for infectivity (franke et al. nature 372:359; thali et al. nature 372:363). we have examined cypa associated with hiv-1mn virions. virions from infected human lymphoid cells were analyzed by high-pressure liquid chromatography (hplc), protein sequence, and immunoblot analysis. at least three forms of cypa were found: an unmodified ...19958554896
hiv acquires functional adhesion receptors from host cells.cd4 is known to serve as the principal cellular receptor for hiv. however, several observations suggest that other molecules may be involved in infection of cells by hiv. cell adhesion molecules and their ligands expressed on hiv-susceptible cells have been implicated in the biology of hiv in a number of studies. we have recently reported that hiv and siv acquire cell adhesion molecules from host cells. we now report that a specific cell adhesion molecule, cd44, that is acquired by hiv retains i ...19958554897
development of a human thymic organ culture model for the study of hiv pathogenesis.the development of effective therapies for the treatment of aids would be facilitated by a better understanding of hiv pathogenesis in vivo. while some aspects of pathogenesis may be assessed by standard tissue culture assays, in vivo animal models may provide clues to other aspects of hiv-mediated progression toward aids. current animal models include primate models for the study of simian immunodeficiency virus (siv) and hiv, scid-hu and hu-pbl scid mouse models for the study of hiv, and felin ...19958554904
sc-52151, a novel inhibitor of the human immunodeficiency virus protease.sc-52151 is a potent, selective, tight-binding human immunodeficiency virus (hiv) protease inhibitor containing the novel (r)-(hydroxyethyl) urea isostere. the mean 50% effective concentration for lymphotropic, monocytotropic strains and field isolates of hiv type 1 (hiv-1), hiv-2, and simian immunodeficiency virus is 26 ng/ml (43 nm). the combination of sc-52151 and nucleoside reverse transcriptase inhibitors synergistically inhibited hiv-1 replication without additive toxicity. an extended pos ...19958619573
interferon treatment inhibits virus replication in hiv-1- and siv-infected cd4+ t-cell lines by distinct mechanisms: evidence for decreased stability and aberrant processing of hiv-1 proteins.we have examined the effects of interferon (ifn)-alpha/beta on hiv-1 and siv replication in cd4+ t-cell lines. to enable us to examine these effects on a single cycle of virus replication, cells were synchronously infected with hiv-1 lai or siv mac251. cell lines included mt4 cells which were responsive to ifn and, as controls, c8166 cells which failed to respond to interferon treatment. similar to previous reports, we found that replication of both hiv-1 and siv was markedly inhibited in respon ...19958553538
both su and tm env proteins are responsible for monkey cell tropism of simian immunodeficiency virus siv mac.while simian immunodeficiency virus (siv) derived from an infectious molecular clone pma239 is tropic and pathogenic for monkeys, the virus derived from another infectious clone pma142 does not replicate in monkey cells. to determine genetic sequences responsible for this tropism, a series of recombinant clones were constructed from pma142 and pma239. the determinant in pma239 was mapped within regions encompassing the env gene. viruses, which carry the 239 env gene encoding surface and/or trans ...19958572945
properties of virus-like particles produced by siv-chronically infected human cell clones.sivsm chronically infected cultures were obtained after infection of cemx174 cells with either sivsmh3 or sivsme660. these phenotypically cd4 cells, formed syncytia but only when cocultivated with cd4+ cells. single cell clones were derived from these cultures and examined for the production of virus-specific proteins. the majority of the clones expressed siv p27 antigen and low levels of virus reverse transcriptase activity. western blot analysis, performed with either monoclonal or polyclonal ...19958574147
antigenicity and immunogenicity of recombinant envelope glycoproteins of sivmac32h with different in vivo passage histories.shortly after infection of two rhesus monkeys (macaca mulatta) either with a sivmac32h challenge stock or with the same virus that had been passaged in another rhesus monkey for 11 months, siv-envelope genes were cloned from their peripheral blood mononuclear cells and subsequently expressed by recombinant vaccinia viruses. the molecular weights and antigenicities of the thus produced envelope glycoproteins were largely identical to those of the native siv. the envelope glycoprotein derived from ...19958578803
hiv interactions with cells of the nervous system.hiv can invade the cns, where it replicates principally in macrophages. yet, neurological disease is more often correlated with levels of neurotoxins or tumor necrosis factor alpha than with viral replication or specific viral determinants in brain. in experimental systems, hiv glycoprotein affects functions of uninfected microglia and astrocytes to eventually cause neuronal death. while the cellular basis of cognitive and neurological dysfunction are unravelled in the simian immunodeficiency vi ...19958580717
potent inhibition of human immunodeficiency virus by mdl 101028, a novel sulphonic acid polymer.mdl 101028, a novel biphenyl disulphonic acid urea co-polymer was designed and synthesised as a heparin mimetic. this low molecular weight polymer showed potent inhibition of human immunodeficiency virus type 1 (hiv-1) replication in a number of host-cell/virus systems, including primary clinical isolates of the virus cultured in human peripheral blood mononuclear cells (pbmcs). when compared with the heterogeneous polysulphated molecules, heparin and dextran sulphate, this chemically defined co ...19958585769
protection from hiv-1 envelope-bearing chimeric simian immunodeficiency virus (shiv) in rhesus macaques infected with attenuated siv: consequences of challenge.to determine whether prior infection with simian immunodeficiency virus (siv)bk28 protects macaques from subsequent exposure to an hiv-1 envelope chimeric siv (shiv). also, to determine the consequences of viral challenge on cd4 numbers and virus load on the current siv infection.19958605046
hepatitis b virus core particles as epitope carriers.hbv core (hbc) particle is one of the most intensively studied particulate carriers for the insertion of foreign peptide sequences. recombinant hbc protein expressed from the cloned gene undergoes the correct folding in a large variety of bacterial, yeast, insect and mammalian cells. unique assembly properties and shape of 30/34-nm hbc particles allow substantial insertions into their primary structure without loss of their capsid-forming ability. n- and c-terminal regions, as well as the immuno ...19958666525
similar patterns of simian immunodeficiency virus env sequences are found in the blood and lymphoid tissues of chronically infected macaques.two cynomolgus macaques were infected with a genetically complex challenge stock of simian immunodeficiency virus (sivmac251-32h). one animal developed siv-induced disease and was sacrificed at 16 months postinfection. the second remained healthy until it too was sacrificed at 20 months postinfection. the polymerase chain reaction (pcr) was used to amplify env gp120-coding sequences from provirus present in samples of blood, spleen, and inguinal lymph node taken from both animals on the day of s ...19958679295
effects of total lymphoid irradiation on siv-infected macaques.the identification of antiretroviral drugs that prevent, or delay for extended periods, progression of hiv-related disease has been of limited success. because the number of hiv-infected people continues to increase, other therapeutic approaches must be tested. using simian immunodeficiency virus (siv)-infected macaques in a feasibility study, total lymphoid irradiation (tli) was administered in fractionated doses to the supradiaphragmatic and then the infradiaphragmatic lymph nodes until a cumu ...19958679296
phylogeny and natural history of the primate lentiviruses, siv and hiv.studies of primate lentivirus phylogeny over the past decade have established a minimum of five related, but genetically distinct, groups of simian immunodeficiency virus (siv), each originating from a different african primate species. the hypothesis that hiv-2 (and sivmac) arose by cross-species transmission from sooty mangabeys (cercocebus atys has been strengthened by a more detailed characterization of the sivsm/sivmac/hiv-2 group of viruses. siv from all four subspecies of african green mo ...19958745080
hippocampal neuronal atrophy occurs in rhesus macaques following infection with simian immunodeficiency virus.there is strong evidence that patients with aids have loss of cortical neurons. in this study we have examined the hippocampus of rhesus monkeys infected with simian immunodeficiency virus (siv) to determine whether neuronal damage occurs in this model of human aids and to investigate its time course. twenty-eight infected monkeys (23 young [< 9 years] and five elderly [> 16 years]) were compared with 11 controls (six young and five elderly). numbers of nucleolated neurons per unit area of secti ...19958745242
low susceptibility of resident microglia to simian immunodeficiency virus replication during the early stages of infection.to assess the susceptibility of resident microglia to simian immunodeficiency virus (siv) infection, we analysed the brains of rhesus macaques after intracerebral (i.c.) inoculation of the virus into the central region at 7 days, 1, 2 and 3 months post-inoculation (p.i.). the brains of animals showed the same moderate neuropathological changes in central, frontal and parietal regions of the brain, characterized by gliosis, microglial nodules, perivascular infiltrates and occasional white matter ...19958745243
isolation and characterization of the first simian immunodeficiency virus from a feral sooty mangabey (cercocebus atys) in west africa.the lineage of hiv-2-like viruses was studied in feral sooty mangabeys (sms) by serological and genetic methods. four feral sooty mangabeys were positive for simian immunodeficiency virus (siv) antibodies and a new isolate, sivsmsl92a, was obtained. genetic analysis of gag genes showed that sivsmsl92a was highly diverse and a distinct sequence subtype within the siv sm/hiv-2 family. the results showed that sivsm is the most diverse group of sivs found thus far in a single monkey species.19958751049
origins of simian immunodeficiency virus infection in macaques at the new england regional primate research center.a cohort of rhesus macaques (macaca mulatta), obtained from the california regional primate research center (crprc) and necropsied in 1970-72 with lesions suggestive of simian immunodeficiency virus (siv) infection, was identified at the new england regional primate research center (nerprc). polymerase chain reaction (pcr), dna sequence analysis, and in situ hybridization were used to confirm the presence of siv nucleic acids. this represents the earliest case of siv infection at the nerprc and ...19958751050
vcam-1 expression and leukocyte trafficking to the cns occur early in infection with pathogenic isolates of siv.this study reports on the endothelial expression of vascular cell adhesion molecule-1 (vcam-1) in the central nervous system (cns) early after experimental infection of rhesus monkeys (macaca mulatta) with pathogenic and nonpathogenic simian immunodeficiency virus (siv). diffuse endothelial expression of vcam-1 was observed in the cns in all animals receiving pathogenic siv. these findings demonstrate the rapidity with which pathogenic siv is able to enter the cns and induce endothelial cell act ...19958751051
assessing genetic-based therapies for aids using the simian immunodeficiency virus.a plasmid encoding the full-length infectious molecular proviral clone of sivmac239 was generated. virus derived from cells transfected with this clone replicated to high levels and was cytopathic for some transformed human cd4+ cell lines and primary rhesus macaque peripheral blood mononuclear cells. since replication of siv requires the functional expression of the viral encoded rev protein, transient co-transfection studies were initiated with the infectious proviral clone and a well-characte ...19958751053
neutralising epitopes of simian immunodeficiency virus envelope glycoprotein.monoclonal and polyclonal antibodies with weak siv neutralising activity bind to the v2 and v4 regions of gp120 or bind to the amino acids dwnnd in gp41. antibodies with the most potent neutralising activity recognise conformation-dependent epitopes involving the v3 and v4 regions of gp120. monoclonal antibodies that map to the v3 region of sivmac failed to neutralise. however, one antibody to siv agm neutralised but only in the presence of soluble cd4.19958751054
[progress in vaccination against aids].two vaccination trials against aids viruses are reported. the first trial was a prophylactic vaccination carried out in the pig-tailed macaque (macacca nemestrina) against simian immunodeficiency virus (siv) variant pbj14. the immunogen was a semliki forest virus (sfv) recombinant expressing sfv - pbj14 envelope protein. vaccination did not prevent infection but protected the animals against the disease (a fulminant form of aids that kills the animal within 12-15 days). the second trial was a th ...19958845793
defective hiv may hold clue to effective vaccine.research studies indicate that the lack of an intact nef gene is responsible for the low levels of hiv in the blood of long-term non-progressors. other research shows that deleting nef from the simian immunodeficiency virus (siv) renders the life-threatening virus harmless, potentially making it possible to create a human vaccine from nef-deleted hiv. some researchers are opposed to this because of the danger of using a live attenuated hiv vaccine.199511363018
pmpa in perspective.pmpa, an experimental anti-hiv drug, is a member of a new class of drugs called nucleotide analogs. pmpa gained attention when it was reported that it completely protected macaque monkeys from siv (a virus closely related to hiv). no other potential treatment has been able to do this. it is difficult to tell how quickly nucleotide analogs can work because, for unknown reasons, viral loads show only modest reductions even when other information suggests that they may be working better than the vi ...199511363050
functionality of chimeric rev proteins of hiv/siv.studies on functional compatibility of various rev proteins derived from all known human and simian immunodeficiency virus subgroups have shown that this essential gene product is not always exchangeable among the viruses. in an attempt to map the region of rev proteins responsible for the observed nonreciprocal complementation, hybrid genomic rev expression vectors were constructed by exchanging the first and second exons of rev genes, and were examined for their abilities to activate reporter ...19958808329
retrovirus and filovirus "immunosuppressive motif" and the evolution of virus pathogenicity in hiv-1, hiv-2, and ebola viruses.the "immunosuppressive motif" was found to be present in the glycoproteins of retroviruses and filoviruses. this sequence is also conserved in the pathogenic lentiviruses, hiv-1 and siv, and is absent from hiv-2 gp41 and from an apathogenic simian retrovirus. the present analysis deals with the possible involvement of the "immunosuppresessive motif" in the pathogenicity of retroviruses and filoviruses, and the reasons for the conservation of this motif. the ancestral gene from which the "immunos ...19958828145
t-helper reactivity to simian immunodeficiency virus gag synthetic peptides in human immunodeficiency virus type 2 infected individuals.west african populations are infected with divergent strains of human immunodeficiency virus type 2 (hiv2), some of which are closely related to simian immunodeficiency virus (siv) and it has been postulated that the hiv2 epidemic might have arisen by cross-species spread of siv into the human population in west africa. to gain some insight into the possible basis for cross protection between these two closely related viruses, the t-helper responses to 15 synthetic peptides from siv gag syntheti ...19958830117
receptor function of cd4 structures from african green monkey and pig-tail macaque for simian immunodeficiency virus, sivsm, sivagm, and human immunodeficiency virus type-1.differences in kinetics of infection, cellular tropism, and cytopathology of siv and hiv appear to depend on both viral and host factors. we investigated the role of critical cd4 structures from african green monkeys (agm) a natural siv host, from pig-tailed macaques (pt) an unnatural siv host, and from humans, as well as the role of species-specific cellular factors involved in the tropism, kinetics of infection, and cytopathic effects of several siv and hiv-1. critical regions of the pt macaqu ...19958833265
follicular dendritic cells productively infected with immunodeficiency viruses transmit infection to t cells.lymphoid organs have been proposed to function as the major reservoir for the human immunodeficiency virus type 1 (hiv-1). within lymphatic tissues germinal centers represent foci of rapidly proliferating b cells governed by the interaction between b and t cells and follicular dendritic cells (fdc). accumulating evidence suggests an important role of fdc in the pathophysiology of the acquired immunodeficiency syndrome. direct proof for the infectibility of fdc with hiv-1 has been lacking until r ...19958577313
the in vitro ejection of zinc from human immunodeficiency virus (hiv) type 1 nucleocapsid protein by disulfide benzamides with cellular anti-hiv activity.several disulfide benzamides have been shown to possess wide-spectrum antiretroviral activity in cell culture at low micromolar to submicromolar concentrations, inhibiting human immunodeficiency virus (hiv) type 1 (hiv-1) clinical and drug-resistant strains along with hiv-2 and simian immunodeficiency virus [rice, w. g., supko, j. g., malspeis, l., buckheit, r. w., jr., clanton, d., bu, m., graham, l., schaeffer, c. a., turpin, j. a., domagala, j., gogliotti, r., bader, j. p., halliday, s. m., c ...19968577770
progesterone implants enhance siv vaginal transmission and early virus load.simian immunodeficiency virus (siv) can cross the intact vaginal epithelium to establish a systemic infection in macaques (mac). using this sivmac model, we found that subcutaneous progesterone implants, which could mimic hormonally based contraceptives, thinned the vaginal epithelium and enhanced siv vaginal transmission 7.7-fold over that observed in macaques treated with placebo implants and exposed to siv in the follicular phase of the menstrual cycle. progesterone treatment also increased t ...19968837605
transient expression of cd20 antigen (pan b cell marker) in activated lymph node t cells.in contrast to the case of peripheral t cells, the surface expression of cd20 antigen and the expression of cd20 mrna in monkey lymph node (ln) t cells underwent a noticeable increase when they were cultured with mitogen and interleukin-2 (il-2). to confirm in vivo regulation of cd20 expression during the activation of ln t cells, we examined lns derived from monkeys experimentally inoculated with simian immunodeficiency virus (siv). significant expression of cd20 antigen was detected in the t c ...19968839435
three-dimensional structures of hiv-1 and siv protease product complexes.strain is eliminated as a factor in hydrolysis of the scissile peptide bond by human immunodeficiency virus (hiv)-1 and simian immunodeficiency virus (siv), based on the first eight complexes of products of hydrolysis with the enzymes. the carboxyl group generated at the scissile bond interacts with both catalytic aspartic acids. the structures directly suggest the interactions of the gemdiol intermediate with the active site. based on the structures, the nucleophilic water is displaced stereosp ...19968841139
a model for alignment of env v1 and v2 hypervariable domains from human and simian immunodeficiency viruses.hiv-1 env gene encodes a multifunctional glycoprotein that is involved in virus infectivity, interactions between the virus and the host immune system, and phenotypic characteristics of virus isolates in culture. a number of env functions map by genetic analysis to v3, one of five hypervariable domains that compose the surface component of env gp120. v1 and v2 hypervariable domains of env also contribute to the phenotype of hiv-1, although relationships between v1 and v2 genotypes and biological ...19968844021
cdc42 and rac1 are implicated in the activation of the nef-associated kinase and replication of hiv-1.the negative factor (nef) of human and simian immunodeficiency viruses (hiv-1, hiv-2 and siv) is required for high levels of viremia and progression to aids. additionally, nef leads to cellular activation, increased viral infectivity and decreased expression of cd4 on the cell surface. previously, we and others demonstrated that nef associates with a cellular serine kinase (nak) activity. recently, it was demonstrated that nak bears structural and functional similarity to p21-activated kinases ( ...19968994833
the role of major histocompatibility complex polymorphisms on siv infection in rhesus macaques.to investigate whether major histocompatibility complex (mhc) polymorphisms influence either susceptibility to siv infection or progress to actual disease, rhesus monkeys were subjected to various forms of siv infection and screened for allelic mhc heterogeneity by means of serological and biochemical methods. animals that are protected against cell associated virus challenges were those that are siv vaccinated and which shared a particular mhc class i allele (mamu-a26) with the donor of the inf ...19968811342
sivagm infection of its natural african green monkey host.possible reasons for the apathogenicity of simian immunodeficiency virus (sivagm) in its natural african green monkey (agm) host were investigated. in most respects, the sivagm/agm system was shown to resemble human immunodeficiency virus type 1 (hiv-1) infection of humans. agms were shown to respond to infection with immune responses similar to those seen in hiv-1-infected humans, with no obvious controlling mechanism observed. the rate of sivagm in vivo variability was likewise shown to be con ...19968811345
immunological and virological studies of natural siv infection of disease-resistant nonhuman primates.nonhuman primates naturally infected with simian immunodeficiency virus (siv), while maintaining chronic viremia, do not develop any disease associated with lentiviral infection. thus they provide a unique model to define the mechanism(s) by which they remain infected but disease-resistant. the purpose of this article is to summarize our current knowledge of the virological and immunological studies that have been performed in sooty mangabeys naturally infected with sivsmm and in disease-suscept ...19968811346
broad cross-neutralizing activity in serum is associated with slow progression and low risk of transmission in primate lentivirus infections.sera from human immunodeficiency virus type 1 and type 2 (hiv-1 and hiv-2)-infected humans were tested with autologous (from the same individual) and heterologous (from other individuals) virus isolates in a neutralization assay. similarly, sera from experimentally simian immunodeficiency virus (sivsm from sooty mangabey) or hiv-2sbl6669-infected cynomolgus macaques were tested for neutralizing activity against autologous and heterologous reisolates. in the neutralization assay, the virus dose r ...19968811351
passive immune globulin therapy in the siv/macaque model: early intervention can alter disease profile.one of the major questions in aids is the role that the host immune system and the virus play in the dynamics of infection and the development of aids in an infected individual. in order to test the role of antibody in controlling viral infection, high-dose siv-immune globulin was passively transferred to infected macaques early in infection. immune globulin purified from the plasma of an siv-infected long-term non-progressor macaque (sivig) or a pool of normal immune globulin (normal ig) was in ...19968811353
recombinant subunit vaccines as an approach to study correlates of protection against primate lentivirus infection.using pathogenic simian immunodeficiency virus (siv) infection of macaques as a model, we explored the limits of the protective immunity elicited by recombinant subunit vaccines and examined factors that affect their efficacy. envelope gp 160 vaccines, when used in a live recombinant virus-priming and subunit-protein-boosting regimen, protected macaques against a low-dose, intravenous infection by a cloned homologous virus sivmne e11s. the same regimen was also effective against intrarectal chal ...19968811354
attenuated siv imparts immunity to challenge with pathogenic spleen-derived siv but cannot prevent repair of the nef deletion.to date, some success has been achieved with several experimental vaccines against aids in the available animal models. in the simian immunodeficiency virus (siv) macaque model protection against superinfection was obtained by preinfection with a virus attenuated by a deletion in nef. to investigate the efficacy of sivmac32h(pc8), a nef deletion mutant of sivmac251, as a live-attenuated vaccine, rhesus monkeys were infected intravenously (i.v.) with this virus. all monkeys became productively in ...19968811357
initiation of (-) strand dna synthesis from trna(3lys) on lentiviral rnas: implications of specific hiv-1 rna-trna(3lys) interactions inhibiting primer utilization by retroviral reverse transcriptases.initiation of minus (-) strand dna synthesis was examined on templates containing r, u5, and primer-binding site regions of the human immunodeficiency virus type 1 (hiv-1), feline immunodeficiency virus (fiv), and equine infectious anemia virus (eiav) genomic rna. dna synthesis was initiated from (i) an oligoribonucleotide complementary to the primer-binding sites, (ii) synthetic trna(3lys), and (iii) natural trna(3lys), by the reverse transcriptases of hiv-1, fiv, eiav, simian immunodeficiency ...19968816751
strategies for aids vaccines.in the global aids epidemic, over half of all infections have occurred in people less than 25 years old resulting in profound social, economic and demographic consequences. current estimates indicate that the present 15 million hiv infections will increase to over 30 million by the end of the millennium. for most countries a safe and effective vaccine offers the only hope of controlling the spread of this disease. the development of an effective vaccine against hiv is beset with formidable obsta ...19968818840
protection against mucosal sivsm challenge in macaques infected with a chimeric siv that expresses hiv type 1 envelope.in a monkey model we used a chimeric siv expressing the hiv-1 envelope gene (shiv-4) as a live attenuated vaccine and a virulent sivsm as a mucosal challenge. four cynomolgus monkeys were inoculated intravenously with shiv-4. virus was repeatedly isolated from blood mononuclear cells of all four animals for 2 to 7 months after the inoculation of shiv. all monkeys developed neutralizing antibodies to hiv-1 and high antibody titers to hiv-1 envelope glycoproteins. in contrast, no neutralizing anti ...19968827215
neurovirulent simian immunodeficiency virus infection induces neuronal, endothelial, and glial apoptosis.studies of human immunodeficiency virus type 1 (hiv-1) associated dementia have shown neuronal loss in discrete areas. the presence and mechanism of neuronal death, however, has remained quite elusive. one mechanism of cell death, apoptosis, has been clearly demonstrated outside the central nervous system (cns) in hiv-1 infection but has not been firmly established within the cns. therefore, we set out to ascertain whether neuronal cell loss in simian immunodeficiency virus (siv) encephalitis, a ...19968827712
rapid development of vaccine protection in macaques by live-attenuated simian immunodeficiency virus.convincing data on experimental vaccines against aids have been obtained in the simian immunodeficiency virus (siv) macaque model by preinfection with a virus attenuated by a nef deletion. to investigate the efficacy of a nef deletion mutant of sivmac32h called pc8 as a live-attenuated vaccine after shorter preinfection periods and to learn more about the nature of the immune protection induced, eight rhesus monkeys were infected intravenously with the pc8 virus. all monkeys became persistently ...19969000087
cdc to revisit azt, post-exposure guidelines. centers for disease control and prevention.the centers for disease control and prevention (cdc) plans to update its guidelines on management of occupational exposure to hiv and will reopen the issue of using azt as prophylaxis. increasing evidence shows that workers occupationally exposed to hiv do not seroconvert when given azt as prophylaxis. additionally, animal research has shown pmpa to provide complete prophylaxis against simian immunodeficiency virus in macaque monkeys.199611363228
progesterone-hiv link questioned by new studies.several small studies conducted by the centers for disease control and prevention (cdc) have shown that although progesterone appears to increase the likelihood of simian immunodeficiency virus (siv) transmission in exposed monkeys, women using hormone contraceptives do not appear to have the same increased risk for hiv. the results, published in the may issue of science, show little, if any, increase in the rate of hiv infection in women on depo-provera, an injectable contraception containing p ...199611363549
advice for women seeking progesterone counseling.after a recent study showing that monkeys given progesterone are more likely to acquire simian immunodeficiency virus (siv), women's reproductive health experts are advising clinicians to stress the importance of condom use and calm worried women by pointing out that other studies are needed to understand the relationship between hormones and hiv risk. researchers have learned that progestin causes a thinning of the vaginal wall--possibly an explanation for the increase in siv infection in the m ...199611363550
highlights of aids vaccine meeting.highlights from the conference on advances in aids vaccine development: 1996 at the national institutes of health (nih) on february 11-15, 1996, are described. the need for cooperation from both government and industry in the search for new treatments and a vaccine for hiv was emphasized. scientists discussed the development of a genetic tree that may help organize the genetically diverse mix of strains worldwide and concluded that recombination will continue to be an important variable in aids ...199611363795
the riddle of oral sex.oral sex continues to be a source of confusion in determining its risk for hiv transmission. educator dave nimmons concludes that oral sex offers a possible, but very low, risk of hiv infection and states that much of the concern about oral sex and hiv prevention centers around two dozen cases of single occurrences of oral transmission from all over the world. many researchers believe that knowledge about this small number of cases facilitates informed decisions about risk and demonstrates under ...199611363848
researchers warn oral sex riskier than expected.recent study results indicate that the risk of hiv transmission from unprotected oral sex may be higher than previously reported. a research group from the university of washington department of medicine in seattle completed a study published in the august 15, 1996 issue of annals of internal medicine. researchers enrolled 43 men, mostly homosexuals, and three women who had acquired hiv in the previous few months. the study aimed to describe events that led to their infection. unprotected oral-g ...199611363849
ap1-related factors interact with simian immunodeficiency virus long terminal repeats.the sf1 element (nucleotide -135 to -131) in the u3 region of the simian immunodeficiency virus (siv) 5' to the nf-kappab binding site plays a role in basal expression of siv [winandy et al., j virol 66:5216-5223, 1992]. using the electrophoretic mobility shift assay, we have characterized a specific sf1 binding factor (sf1) in the nuclear fractions of transformed t cells as well as monocytic and macrophage leukemic cells. a strong sf1 binding activity was demonstrated in all cell types. the sf1 ...199611725097
a block to efficient replication of simian immunodeficiency virus in c8166 cells can be overcome by duplication of the nf-kappab binding site.sequence analysis of the acutely lethal pbj14 strain of simian immunodeficiency virus (sivpbj14) clone revealed among other differences from its less pathogenic counterparts a duplication of its binding site for nuclear factor kappa b (nf-kappab) in its long terminal repeats (ltr). we have investigated whether introducing a similar duplication into the pathogenic molecular clone siv mac239 would alter its biological properties. we compared an siv which possessed 2 nf-kappab sites to the wild typ ...199611725122
the nef gene of sivmac239 is necessary for efficient growth in h9 cells.aids viruses require an intact functional nef gene in order to induce disease. the nonpathogenic molecular cloned virus sivmac239nef-deletion encodes a truncated nef gene. this attenuated reading frame is expressed both in vitro and in a virus-infected animal in vivo. encoding the first 58 amino acids of nef, the reading frame retained its ability to down-modulate cd4 from the surface of t cells. cd4-down-modulated stable cell lines expressing full-length and truncated nef genes were significant ...199611725123
does progesterone increase hiv risk? contraceptive update.the recent finding that rhesus monkeys given progesterone were more likely to become infected after vaginal exposure to simian immunodeficiency virus than their nontreated counterparts has raised concerns about the effect of progestin-containing contraceptives on hiv risk. more research is needed to determine whether this finding extends to the progestins used in oral contraceptives, norplant, injectables, and the levonorgestrel-containing iud. family health international, in response to the a ...199612291587
hormonal contraceptives and the risk of stds.a recent national institutes of health (nih)-funded study indicating that rhesus monkeys implanted with long-acting progesterone pellets were more likely to become infected after vaginal exposure to simian immunodeficiency virus (siv) than their nontreated counterparts has raised concerns about the contribution of hormonal contraception to sexually transmitted disease (std) risk. 14 of 18 monkeys treated with progesterone, compared with only 1 of 10 controls, developed siv. researchers specula ...199612291588
virus-induced immunosuppression is linked to rapidly fatal disease in infant rhesus macaques infected with simian immunodeficiency virus.six newborn rhesus macaques were experimentally infected with pathogenic simian immunodeficiency virus of macaques (sivmac251), and three newborn macaques were infected with avirulent sivmac1a11. the former developed rapidly fatal simian aids and died within 26 wk of age, whereas the latter remained clinically normal. infant monkeys that developed rapidly progressive disease had rapid declines in cd4+ cells and were unable to mount igg and iga antibody responses to siv or to an unrelated antigen ...19968848337
induction of siv capsid-specific ctl and mucosal siga in mice immunized with a recombinant s. typhimurium aroa mutant.we have developed a new expression system based on the e. coli groel promoter. the suicide vector constructed (called apc vector) allows simultaneous attenuation of a salmonella strain by disruption of the coding sequence for aroa and stable integration of a gene into the bacterial chromosome. high-level expression of antigen is achieved after salmonella is taken up by macrophages, a major antigen processing cell of the host. the chloramphenicol acetyltransferase (cat) and the simian immunodefic ...19968852411
safety of 9-(2-phosphonylmethoxyethyl)adenine (pmea) in patients with human immunodeficiency virus infection: a pilot study.the compound 9-(2-phosphonylmethoxyethyl)adenine (pmea) is a potent inhibitor of a number of viruses in vitro such as human immunodeficiency virus types 1 and 2, herpes simplex virus types 1 and 2, hepatitis b virus, cytomegalovirus, and epstein-barr virus. pmea also proved to be effective in vivo against feline immunodeficiency virus in cats and simian immunodeficiency virus in rhesus monkeys. in an open, non-placebo-controlled trial, the safety of weekly doses of pmea in 10 patients with acqui ...19968861829
elevated venous glutamate levels in (pre)catabolic conditions result at least partly from a decreased glutamate transport activity.abnormally high postabsorptive venous plasma glutamate levels have been reported for several diseases that are associated with a loss of body cell mass including cancer, human/simian immunodeficiency virus infection, and amyotrophic lateral sclerosis. studies on exchange rates in well-nourished cancer patients now show that high venous plasma glutamate levels may serve as a bona fide indicator for a decreased uptake of glutamate by the peripheral muscle tissue in the postabsorptive period and ma ...19968862515
direct amplification and cloning of up to 5-kb lentivirus genomes from serum.to produce large cdna strands from biological samples containing limited numbers of template molecules, it may be necessary to minimize both nonspecific primer attachment in first-strand synthesis and secondary structure in rna molecules. failure to do so could result in the accumulation of shortened cdna strands and therefore may reduce the yield of large cdna molecules, sometimes below detection level. we show that 5.0-kb cdna fragments can be generated from simian immunodeficiency virus rna i ...19968862818
localization of simian immunodeficiency virus nucleic acid and antigen in brains of fetal macaques inoculated in utero.neurological dysfunction has been shown to be associated with human immunodeficiency virus (hiv) infection. the incidence of these abnormalities is greater in hiv-infected children when compared with adults, and the patterns of neurological disease are also known to differ from those observed in the adult population. the reasons for these differences are unclear but are most likely related to the immaturity of the host's immune and central nervous systems at the time of infection. this is though ...19968863658
the effect of recombinant human interferon alpha b/d compared to interferon alpha 2b on siv infection in rhesus macaques.the model of simian immunodeficiency virus (siv) infection in rhesus macaques was used to evaluate the effects of recombinant human interferon alpha, hu ifn-alpha 2b and hu ifn-gamma b,d, at two doses. administration began 1 day prior to infection and was continued for 90 days postinfection. both interferons suppressed siv antigenemia during the treatment period. following treatment animals were monitored for 4 years for rate of disease progression. neither ifn prolonged the asymptomatic period ...19968863990
neuropathology of early hiv-1 infection.early hiv-1 invasion of the central nervous system has been demonstrated by many cerebrospinal fluid studies; however, most hiv-1 carriers remain neurologically unimpaired during the so called "asymptomatic" period lasting from seroconversion to symptomatic aids. therefore, neuropathological studies in the early pre-aids stages are very few, and the natural history of central nervous system changes in hiv-1 infection remains poorly understood. examination of brains of asymptomatic hiv-1 positive ...19968866743
cytokine mrna expression in mononuclear cells from different tissues during acute sivmac251 infection of macaques.we used semiquantitative rt-pcr to monitor the expression of mrna encoding cytokines (il-1 beta, il-6, tnf-alpha, and il-10) and ifn-gamma in fresh isolated peripheral blood mononuclear cells (pbmcs), lymph node mononuclear cells (lnmcs), and mononuclear cells obtained after bronchoalveolar lavages (balmcs), of four cynomolgus macaques inoculated intravenously with a pathogenic isolate of simian immunodeficiency virus (sivmac251). to investigate the effects of the viral load on the expression of ...19968870848
the relationship between the interferon alpha response and viral burden in primary siv infection.the interferon alpha (ifn-alpha) response of rhesus macaques was investigated during primary infection with pathogenic and attenuated simian immunodeficiency virus (siv). ifn-alpha was detected in the serum of animals as early as day 4 after inoculation of sivmac251, but remained barely detected in animals infected with the attenuated virus sivmac251 delta nef. the peak of ifn-alpha secretion preceded that of antigenemia in animals infected with pathogenic virus, indicating that the ifn-alpha re ...19968870849
il-15 stimulates the expansion of aids virus-specific ctl.it has been assumed that the maturation of pre-ctl to virus-specific effector ctl is dependent upon il-2-mediated t cell triggering through the il-2r. in view of its similarity to il-2 in its effects on immune cells, we sought to determine whether il-15 can induce the expansion of aids virus-specific pre-ctl to mature ctl. pbl of siv(mac)-infected rhesus monkeys or hiv-1-infected humans have previously been shown to expand to effector ctl when cultivated with a predicted ctl epitope peptide and ...19968871670
the v3 domain of sivmac251 gp120 contains a linear neutralizing epitope.antisera to 21 synthetic peptides containing hydrophilic sequences of simian immunodeficiency virus strain mac251 (sivmac251) gp120 and gp32 were tested for the ability to neutralize sivmac251. goat antisera raised to peptides sp-1 and sp-1v containing the carboxy-terminal portion of the v3 domain of sivmac251 gp120 between amino acids 327 and 339 inhibited syncytium formation (90% inhibition at a 1/1024 dilution) and cell killing of cemx174 cells by sivmac251 (50%) inhibition of cell killing at ...19968874502
role of mason-pfizer monkey virus (mpmv) constitutive transport element (cte) in the propagation of mpmv vectors by genetic complementation using homologous/heterologous env genes.to study mason-pfizer monkey virus (mpmv) replication over a single round, virus particles were generated that contain a replication-defective vector encoding a dominant selectable marker, the hygromycin b phosphotransferase (hyg) gene. genetic complementation with a homologous mpmv envelope glycoprotein (env-gp) or pseudotyping by several heterologous env-gps from a variety of viruses resulted in infectious mpmv particles containing the replication-defective rna. recently, it has been shown tha ...19968874512
human immunodeficiency virus (hiv) nef is an rna binding protein in cell-free systems.the function of human immunodeficiency virus nef gene product has been much debated but the precise activity of this protein in the hiv replication cycle remains unknown. hiv-1 nef was obtained as a fusion protein with maltose binding protein (mbf), purified by amylose column chromatography and separated from mbp by cleavage with factor xa. purified hiv-1 nef protein, but not the fusion protein mbp-nef, binds to rna in vitro as tested by three different assays, radioactive or non-radioactive. no ...19968876644
functional analysis of simian immunodeficiency virus sivagm long terminal repeat.we have previously shown that long terminal repeats (ltrs) derived from various isolates of sivagm share a unique functional property. in the absence of viral tat, all sivagm ltrs act as much more efficient promoters than any of the other ltrs derived from representative primate immunodeficiency viruses. in the presence of tat, however, sivagm ltrs are activated relatively inefficiently. to map the elements that confer these features on the sivagm ltr, a number of deletion mutants were construct ...19968879117
protection against human immunodeficiency virus type 2 and simian immunodeficiency virus in macaques vaccinated against human immunodeficiency virus type 2. 19968882330
simian immunodeficiency virus live and inactivated experimental vaccines. 19968882331
"attenuated" simian immunodeficiency virus in macaque neonates. 19968882333
highly sensitive qualitative and quantitative detection of reverse transcriptase activity: optimization, validation, and comparative analysis with other detection systems.an ultra-sensitive assay for reverse transcriptase (rt) activity called amp-rt has been developed. an in vitro transcribed heteropolymeric rna sequence was used as a template, and polymerase chain reaction (pcr) amplification with southern-blot hybridization served as a detection system for the cdna product of the reaction. titration of mg2+ and mn2+ concentrations using the human immunodeficiency virus type 1 (hiv-1) and the human t lymphotropic virus type 1 (htlv-i), respectively, showed optim ...19968882946
replication and cytopathogenicity of human immunodeficiency virus type 1 (hiv-1)/simian immunodeficiency virus agm3 chimeric viruses in human and monkey cells: the 5' half of the hiv-1 genome is responsible for virus cytopathogenicity.two chimeric viruses were constructed between human immunodeficiency virus type 1 (hiv-1) and an apathogenic simian immunodeficiency virus (sivagm3mc) from african green monkeys. one of the chimeras, he-a391, expressed the hiv-1-derived env, vpu, tat and rev genes and the sivagm3mc-derived ltr and the gag, pol and vif genes. the other chimera, se-h13, contained the sivagm3mc-derived env, tat and rev genes and the hiv-1-derived ltr and the gag, pol, vif and nef genes. both constructs yielded infe ...19968887473
t cell apoptosis in human immunodeficiency virus type 2- and simian immunodeficiency virus-infected macaques.recent evidence suggests that t cell apoptosis could be involved in the pathogenesis of hiv infection. in addition, lymphocyte apoptosis has been described in siv-infected macaques that developed simian aids. to investigate further the role of apoptosis in aids pathogenesis, we studied lymphocytes of hiv-2-infected cynomolgus macaques that did not develop simian aids. we compared apoptosis of lymphocytes from animals infected with non-pathogenic hiv-2 to that in macaques infected with pathogenic ...19968887474
the history of simian aids.retrospective data indicate that two separate outbreaks of simian aids and associated lymphoma were caused by simian immunodeficiency virus (sivmac and sivstm, respectively) in group-housed macaques at the california regional primate research center (crprc) in the early and mid-1970s. because these epizootics were not then recognized as infectious in nature, surviving healthy siv carriers were sent to other primate centers where they transmitted the viruses to resident macaques. the source of si ...19968892035
do cytotoxic t lymphocytes clear some hiv/siv infections?early work on the roles of cytotoxic t lymphocytes (ctls) in acute viral infections in animal models showed that i) the clearance of virus coincided with the increase in ctl activity rather than specific antibody levels, ii) transfer of ctls after infection could protect from a lethal dose of virus, and iii) in primed, compared to naive, animals, ctl activity appeared 1-3 days earlier after a challenge infection. there is now a series of findings with individuals who have been exposed to hiv but ...19968892036
the value of primate models for studying human immunodeficiency virus pathogenesis.research on human immunodeficiency virus (hiv) infection is compromised by the obvious limitation in having for study only virus-infected individuals or those exposed to the virus. steps involved in transmission or pathogenesis require planned experimentation. the identification of animal models of acquired immunodeficiency syndrome (aids) has therefore been helpful for evaluating phases of hiv pathogenesis. of the seven subgenera of lentiviruses now recognized, two share the characteristics wit ...19968892037
initial characterization of viral sequences from a shiv-inoculated pig-tailed macaque that developed aids.in this study, we report on the derivation of a pathogenic siv-hiv chimeric virus (shiv) and the initial characterization of the viral sequences from the first (macaque ppc) of a series of pig-tailed macaques that developed cd4+ t cell loss and aids. viral genes were amplified by pcr from the brain, lymphoid, and kidney tissues and their sequences compared to the original shiv used to initiate passages in macaques. our results show that the vpu gene, which was nonfunctional in the original shiv, ...19968892038
immunodeficiency virus cdna synthesis in resting t lymphocytes is regulated by t cell activation signals and dendritic cells.we explored the relationship between t cell activation signals and dendritic cells (dc) in the replication cycle of immunodeficiency viruses. first we analyzed the effect of two cell cycle inhibitors (mimosine and aphidicolin) on siv reverse transcription, circularization, and integration in macaque resting t cells stimulated with anti-cd3 mab at the time of infection. the formation of siv ltr circles was blocked by the g1 inhibitor mimosine. the g1/s inhibitor aphidicolin neither affected circu ...19968892041
genotypic analysis of infant macaques infected transplacentally and orally.the siv-infected macaque provides an excellent model to study factors involved in maternal-fetal transmission of hiv. in our prenatal transmission studies, female macaques were inoculated intravenously during midgestation with either siv/deltab670 or a combination of siv/ deltab670 and the macrophage-tropic molecular clone siv/17e-fr. the females harbored a genetically diverse virus population at parturition, whereas a single genotype from the maternal quasispecies was identified in the infants. ...19968892044
in vivo protective anti-hiv immune responses in non-human primates through dna immunization.an effective immune response involves the specific recognition of and elimination of an infectious organism at multiple levels. in this context dna immunization can present functional antigenic proteins to the host for recognition by all arms of the immune system, yet provides the opportunity to delete any genes of the infectious organism which code for antigens or pieces of antigens that may have deleterious effects. our group has developed the use of nucleic acid immunization as a possible met ...19968892046
infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface.the envelope protein, gp120, of human immunodeficiency virus type 1 (hiv-1) is heavily glycosylated and sialylated. the heavy sialylation greatly affects the physical properties of the protein, as it resolves into a wide acidic ph range despite the basic pi value predicted for its polypeptide backbone (b. s. stein and e. g. engleman, j. biol. chem. 265:2640-2649, 1990). however, the functional significance of the heavy sialylation remains elusive. here, we show that desialylation of hiv-1 with n ...19968892864
cytotoxic t-lymphocyte responses to cytomegalovirus in normal and simian immunodeficiency virus-infected rhesus macaques.disseminated cytomegalovirus (cmv) infection is a frequent occurrence in human immunodeficiency virus-infected humans and in simian immunodeficiency virus (siv)-infected rhesus macaques. rhesus macaques are a suitable animal model with which to study in vivo interactions between cmv and aids-associated retroviruses. since cytotoxic t lymphocytes (ctl) play a major role in control of viral infections, we have characterized cmv-specific ctl responses in siv-infected and uninfected rhesus macaques. ...19968892893
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