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neurovirulent simian immunodeficiency virus incorporates a nef-associated kinase activity into virions.we have demonstrated that a molecular clone, siv/17e-fr, is neurovirulent in vivo and molecular analyses of this virus in primary macrophages and neuroendothelial cells mapped the domains critical for this phenotype to the transmembrane and nef proteins. the nef protein is crucial for virus replication and pathogenesis in siv-infected rhesus macaques. in addition, both hiv and siv require full-length nef proteins for efficient virus replication in primary cells and optimal virion infectivity. to ...19989462927
rapid turnover of t lymphocytes in siv-infected rhesus macaques.studies of lymphocyte turnover in animal models have implications for understanding the mechanism of cell killing and the extent of lymphocyte regeneration in human immunodeficiency virus infection. quantitative analyses of the sequential changes in bromodeoxyuridine labeling of cd4 and cd8 t lymphocytes not only revealed the normal proliferation and death rates of these cell populations in uninfected macaques, but also showed a substantial increase in these rates associated with simian immunode ...19989469816
hiv-1/simian immunodeficiency virus infection of human and nonhuman primate lymphocytes results in the migration of cd2+ t cells into the intestine of engrafted scid mice.increased lymphocytic infiltration of intestinal tissues has been observed in patients infected with hiv-1 and in siv-infected rhesus macaques. to determine whether hiv-1 and siv infections influence the homing of human and nonhuman primate pbmc to intestinal tissues, we engrafted scid mice with human or nonhuman primate pbmc and infected them with either cell-free or cell-associated hiv-1 or siv. in mice that received both pbmc and virus, human or nonhuman primate cd2+ t cells were found in int ...19989498796
chemokine receptor expression on resident and inflammatory cells in the brain of macaques with simian immunodeficiency virus encephalitis.although the mechanisms of human immunodeficiency virus (hiv) neuroinvasion, neuronal injury, and subsequent development of hiv-1-associated aids dementia complex are not fully understood, a correlation between monocyte/macrophage infiltrates in the brain and neurological disease exists. in light of the many potential roles that chemokines and chemokine receptors may play in hiv neuropathogenesis, we sought to describe their pattern of expression in the siv-infected rhesus macaque model of hiv e ...19989502406
in vivo replication capacity rather than in vitro macrophage tropism predicts efficiency of vaginal transmission of simian immunodeficiency virus or simian/human immunodeficiency virus in rhesus macaques.we used the rhesus macaque model of heterosexual human immunodeficiency virus (hiv) transmission to test the hypothesis that in vitro measures of macrophage tropism predict the ability of a primate lentivirus to initiate a systemic infection after intravaginal inoculation. a single atraumatic intravaginal inoculation with a t-cell-tropic molecular clone of simian immunodeficiency virus (siv), sivmac239, or a dualtropic recombinant molecular clone of siv, sivmac239/1a11/239, or uncloned dualtropi ...19989525652
social stress results in altered glucocorticoid regulation and shorter survival in simian acquired immune deficiency syndrome.from early in the aids epidemic, psychosocial stressors have been proposed as contributors to the variation in disease course. to test this hypothesis, rhesus macaques were assigned to stable or unstable social conditions and were inoculated with the simian immunodeficiency virus. animals in the unstable condition displayed more agonism and less affiliation, shorter survival, and lower basal concentrations of plasma cortisol compared with stable animals. early after inoculation, but before the e ...19989539804
gastrointestinal tract as a major site of cd4+ t cell depletion and viral replication in siv infection.human and simian immunodeficiency virus (hiv and siv) replicate optimally in activated memory cd4(+) t cells, a cell type that is abundant in the intestine. siv infection of rhesus monkeys resulted in profound and selective depletion of cd4+ t cells in the intestine within days of infection, before any such changes in peripheral lymphoid tissues. the loss of cd4+ t cells in the intestine occurred coincident with productive infection of large numbers of mononuclear cells at this site. the intesti ...19989545219
administration of recombinant human interleukin 12 to chronically sivmac-infected rhesus monkeys.with the demonstration that interleukin 12 can enhance natural killer (nk) cell activity and drive cd4+ lymphocytes toward t helper type 1 (thl) responses, there is a strong rationale for exploring the use of this cytokine as an immunomodulatory therapy in hiv-1-infected individuals. to assess its potential safety and effects on both immune and virologic aspects of hiv-1 infection, recombinant human il-12 (rhil-12) was assessed in rhesus monkeys chronically infected with the simian immunodeficie ...19989546798
structured-tree topology and adaptive evolution of the simian immunodeficiency virus sivsm envelope during serial passage in rhesus macaques according to likelihood mapping and quartet puzzling.species-specific strains of simian immunodeficiency virus (siv) are nonpathogenic in african primates. the siv strain most closely related to human immunodeficiency virus type 2 (hiv-2) is sivsm, the strain specific to the sooty mangabey (cercocebus atys). infection of asian primates with siv causes aids and allows the study of the adaptive evolution of a lentivirus to replicate efficiently in a new host, providing a useful animal model of hiv infection and aids in humans. serial passage of sivs ...19989557648
natural isolates of simian virus 40 from immunocompromised monkeys display extensive genetic heterogeneity: new implications for polyomavirus disease.simian virus 40 (sv40) dnas in brain tissue and peripheral blood mononuclear cells (pbmcs) of eight simian immunodeficiency virus-infected rhesus monkeys with sv40 brain disease were analyzed. we report the detection, cloning, and identification of five new sv40 strains following a quadruple testing-verification strategy. sv40 genomes with archetypal regulatory regions (containing a duplication within the g/c-rich regulatory region segment and a single 72-bp enhancer element) were recovered from ...19989557685
recombinant vaccine-induced protection against the highly pathogenic simian immunodeficiency virus siv(mac251): dependence on route of challenge exposure.vaccine protection from infection and/or disease induced by highly pathogenic simian immunodeficiency virus (siv) strain siv(mac251) in the rhesus macaque model is a challenging task. thus far, the only approach that has been reported to protect a fraction of macaques from infection following intravenous challenge with siv(mac251) was the use of a live attenuated siv vaccine. in the present study, the gag, pol, and env genes of siv(k6w) were expressed in the nyvac vector, a genetically engineere ...19989557706
generation of cd8 suppressor factor and beta chemokines, induced by xenogeneic immunization, in the prevention of simian immunodeficiency virus infection in macaques.previous xenogeneic immunization experiments in rhesus macaques with simian immunodeficiency virus (siv) grown in human cd4(+) t cells consistently elicited protection from challenge with live siv. however, the mechanism of protection has not been established. we present evidence that xenogeneic immunization induced significant cd8 suppressor factor, rantes (regulated upon activation, normal t cell expressed and secreted), macrophage inflammatory protein (mip) 1alpha, and mip-1beta (p < 0.001 - ...19989560257
immunophenotypic characterization of simian immunodeficiency virus-infected dendritic cells in cervix, vagina, and draining lymph nodes of rhesus monkeys.significant progress has been made in understanding the biology of heterosexual transmission of hiv by utilizing the simian immunodeficiency virus (siv)/rhesus monkey animal model. our previous studies have shown that siv-infected cells within the stratified squamous epithelium of the vagina have a dendritic morphology. however, the type of cell infected was not conclusively determined. the purpose of the present study was to immunophenotype the siv-infected cells in the lower reproductive tract ...19989564888
evidence for the persistence of monoclonal expansions of cd8+ t cells following primary simian immunodeficiency virus infection.a longitudinal study of the cd8+ tcr variable (vbeta) chain repertoire was performed in rhesus macaques experimentally infected with simian immunodeficiency virus (siv) using both tcr vbeta chain-specific monoclonal antibodies and tcr beta chain cdr3 length analysis. expansions of subpopulations of cd8+ t cells were detected during the acute phase of siv infection. in all monkeys studied, monoclonal expansions persisted for at least 18 months and increasingly dominated the repertoire of cd8+ t c ...19989565356
analysis of gag-specific cytotoxic t lymphocytes in simian immunodeficiency virus-infected rhesus monkeys by cell staining with a tetrameric major histocompatibility complex class i-peptide complex.a tetrameric recombinant major histocompatibility complex (mhc) class i-peptide complex was used as a staining reagent in flow cytometric analyses to quantitate and define the phenotype of gag-specific cytotoxic t lymphocytes (ctls) in the peripheral blood of simian immunodeficiency virus macaque (sivmac)-infected rhesus monkeys. the heavy chain of the rhesus monkey mhc class i molecule mamu-a*01 and beta2-microglobulin were refolded in the presence of an sivmac gag synthetic peptide (p11c, c-m) ...19989565630
in vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: cxcr4, ccr3, and ccr5.we have evaluated the in vivo distribution of the major human immunodeficiency virus/simian immunodeficiency virus (hiv/siv) coreceptors, cxcr4, ccr3, and ccr5, in both rhesus macaques and humans. t lymphocytes and macrophages in both lymphoid and nonlymphoid tissues are the major cell populations expressing hiv/siv coreceptors, reaffirming that these cells are the major targets of hiv/siv infection in vivo. in lymphoid tissues such as the lymph node and the thymus, approximately 1 to 10% of the ...19989573273
simian-human immunodeficiency virus (shiv) containing the nef/long terminal repeat region of the highly virulent sivsmmpbj14 causes pbj-like activation of cultured resting peripheral blood mononuclear cells, but the chimera showed no increase in virulence.sivsmmpbj14 is a highly pathogenic lentivirus which causes acute diarrhea, rash, massive lymphocyte proliferation predominantly in the gastrointestinal tract, and death within 7 to 14 days. in cell culture, the virus has mitogenic effects on resting macaque t lymphocytes. in contrast, sivmac239 causes aids in rhesus macaques, generally within 2 years after inoculation. in a previous study, replacement of amino acid residues 17 and 18 of the nef protein of sivmac239 with the corresponding amino a ...19989573293
suppression of viral replication in a long-term nonprogressing rhesus macaque experimentally infected with pathogenic simian immunodeficiency virus (siv). 19989576016
oral siv, shiv, and hiv type 1 infection.several strains of simian immunodeficiency virus (siv), including uncloned and molecularly cloned siv strains, can cross intact mucosal surfaces after oral exposure in both adult and neonatal rhesus macaques, resulting in viremia and disease. cell-free siv strains as well as infected whole blood have resulted in systemic infection after oral inoculation. neonatal macaques, exposed orally to the chimeric shiv-vpu+, a derivative of sivmac239 that encodes the env gene of the t cell-tropic hiv-iiib, ...19989581893
vaginal transmission of siv: assessing infectivity and hormonal influences in macaques inoculated with cell-free and cell-associated viral stocks.cell associated and cell-free simian immunodeficiency virus (siv) were used to investigate transmission of siv across the vaginal mucosa of rhesus macaques. the intact vaginal epithelium was found to be a strong but penetrable barrier to cell-free siv infection. we found that 10,000-fold more cell-free siv was needed to infect 100% of the macaques by the vaginal route when compared to the dose needed to infect 100% by the intravenous (i.v.) route. like cell-free siv, cell-associated siv was an e ...19989581895
induction of mhc-iidr expression on circulating cd8+ lymphocytes in macaques infected with sivmac239 nef-open but not with its nef-deletion mutant.we examined the expression kinetics of activation antigens cd38 and mhc-iidr (dr) on circulating cd8+ lymphocytes in rhesus macaques infected with pathogenic simian immunodeficiency virus strain sivmac239 nef-open (239) or its nonpathogenic nef-deletion mutant (delta nef). in the longitudinal study, we found for the first time the induction of dr expression on cd8+ lymphocytes in 239-infected macaques. the induction of dr was in parallel with an increasing viral load and a decreasing cd4+ lympho ...19989591716
passive immunization of newborn rhesus macaques prevents oral simian immunodeficiency virus infection.to determine if passively acquired antiviral antibodies modulate virus transmission and disease progression in human pediatric aids, the potential of pre- and postexposure passive immunization with hyperimmune serum to prevent oral simian immunodeficiency virus (siv) infection or disease progression in newborn rhesus macaques was tested. untreated neonates became infected after oral siv inoculation and had high viremia, and most animals developed fatal aids within 3 months. in contrast, siv hype ...19989593009
ultrastructure of atypical (teratoid) sporogonial stages of enterocytozoon bieneusi (microsporidia) in naturally infected rhesus monkeys (macacca mulatta).to demonstrate the ultrastructural features of normal and atypical (teratoid) developmental stages of enterocytozoon bieneusi in naturally infected rhesus monkeys (macacca mulatta).19989593343
increased rates of cd4(+) and cd8(+) t lymphocyte turnover in simian immunodeficiency virus-infected macaques.defining the rate at which t cells turn over has important implications for our understanding of t lymphocyte homeostasis and aids pathogenesis, yet little information on t cell turnover is available. we used the nucleoside analogue bromodeoxyuridine (brdurd) in combination with five-color flow cytometric analysis to evaluate t lymphocyte turnover rates in normal and simian immunodeficiency virus (siv)-infected rhesus macaques. t cells in normal animals turned over at relatively rapid rates, wit ...19989600975
early regeneration of thymic progenitors in rhesus macaques infected with simian immunodeficiency virus.the thymus plays a critical role in the maturation and production of t lymphocytes and is a target of infection by human immunodeficiency virus (hiv) and the related simian immunodeficiency virus (siv). using the siv/macaque model of aids, we examined the early effects of siv on the thymus. we found that thymic infection by siv resulted in increased apoptosis 7-14 d after infection, followed by depletion of thymocyte progenitors by day 21. a marked rebound in thymocyte progenitors occurred by da ...19989607918
role of the sh3-ligand domain of simian immunodeficiency virus nef in interaction with nef-associated kinase and simian aids in rhesus macaques.the nef gene of the human and simian immunodeficiency viruses (hiv and siv) is dispensable for viral replication in t-cell lines; however, it is essential for high virus loads and progression to simian aids (saids) in siv-infected adult rhesus macaques. nef proteins from hiv type 1 (hiv-1), hiv-2, and siv contain a proline-xaa-xaa-proline (pxxp) motif. the region of nef with this motif is similar to the src homology region 3 (sh3) ligand domain found in many cell signaling proteins. in virus-inf ...19989621042
a role for carbohydrates in immune evasion in aids.rhesus monkeys were infected with mutant forms of simian immunodeficiency virus lacking dual combinations of the 4th, 5th and 6th sites for n-linked glycosylation in the external envelope glycoprotein of the virus. when compared with sera from monkeys infected with the parental virus, sera from monkeys infected with the mutant viruses exhibited markedly increased antibody binding to specific peptides from this region and markedly increased neutralizing activity. these results demonstrate a role ...19989623976
social separation, housing relocation, and survival in simian aids: a retrospective analysis.to test the hypothesis that changes in housing, particularly those involving social separations, would have a negative impact on survival in rhesus monkeys experimentally inoculated with the simian immunodeficiency virus (siv).19989625208
impaired responses to mycobacterium leprae antigens in rhesus monkeys experimentally inoculated with simian immunodeficiency virus and m. leprae.seven of eight rhesus monkeys (rm) coinfected with simian immunodeficiency virus (siv) and mycobacterium leprae harboured acid-fast bacilli (afb) at sites of dermal inoculation and/or at disseminated sites at times of humane sacrifice (up to 270 days post-m. leprae inoculation) due to siv-induced debilitation or, in one long term survivor's case, to date over 3 years post-m. leprae inoculation. detectable afb were cleared in biopsies of inoculation sites of rm inoculated with m. leprae alone aft ...19989628093
infection of baboons with a simian immunodeficiency virus/hiv-1 chimeric virus constructed with an hiv-1 thai subtype e envelope.to construct an infectious chimeric simian immunodeficiency virus/hiv-1 (shiv) with the envelope of a thai subtype e hiv-1 strain for use in a non-human primate model.19989631137
characterization of the peptide binding motif of a rhesus mhc class i molecule (mamu-a*01) that binds an immunodominant ctl epitope from simian immunodeficiency virus.the majority of immunogenic ctl epitopes bind to mhc class i molecules with high affinity. however, peptides longer or shorter than the optimal epitope rarely bind with high affinity. therefore, identification of optimal ctl epitopes from pathogens may ultimately be critical for inducing strong ctl responses and developing epitope-based vaccines. the siv-infected rhesus macaque is an excellent animal model for hiv infection of humans. although a number of ctl epitopes have been mapped in siv-inf ...19989637523
simian immunodeficiency virus encephalitis in rhesus macaques is associated with rapid disease progression.central nervous system (cns) disease is a major feature of simian immunodeficiency virus (siv) infection of macaques. to define the spectrum of cns lesions in siv-infected macaques and the potential associations with viral strain and disease course, we performed a retrospective analysis of necropsies on 124 macaques with siv-induced aids. histologic evidence of cns disease was observed in 71 (57.3%) of the 124 animals. siv encephalitis was the most common cns lesion occurring in 43.7% (31/71) of ...19989639069
hypervariable epitope constructs representing variability in envelope glycoprotein of siv induce a broad humoral immune response in rabbits and rhesus macaques.using synthetic peptides, we developed an approach to account for protein epitope variability. we have prepared, in a single synthesis, a cocktail of peptides we have designated a hypervariable epitope construct (hec), which collectively represents much of the in vivo variability seen in an epitope. eight hecs representing the in vivo variability seen throughout the envelope glycoprotein of the simian immunodeficiency virus (siv) were designed and synthesized. the constructs were collectively co ...19989643375
administration of 9-[2-(phosphonomethoxy)propyl]adenine (pmpa) for prevention of perinatal simian immunodeficiency virus infection in rhesus macaques.simian immunodeficiency virus (siv) infection of newborn macaques is a useful animal model to explore novel strategies to reduce perinatal human immunodeficiency virus (hiv) infection. the availability of two easily distinguishable virus isolates, sivmac251 and the simian/human immunodeficiency virus chimera shiv-sf33, allows tracing the source of infection following inoculation with both viruses by different routes. in the present study, we evaluated the efficacy of pre- and postinoculation tre ...19989643376
administration of interleukin 13 to simian immunodeficiency virus-infected macaques: induction of intestinal epithelial atrophy.increase th2 cytokine production may contribute to some clinical manifestations of hiv infection, and studies have suggested that il-13 rather than il-4 is involved in these conditions. we directly tested this hypothesis by administrating il-13 to siv-infected macaques. siv-infected rhesus macaques received a daily subcutaneous injection for 21 days of either il-13 (10 microg/kg/day) or a placebo. the four macaques treated with il-13 experienced body weight loss (9.95 +/- 0.71%) related to intes ...19989643377
inhibition of simian immunodeficiency virus (siv) replication by cd8(+) t lymphocytes from macaques immunized with live attenuated siv.characterization of immune responses induced by live attenuated simian immunodeficiency virus (siv) strains may yield clues to the nature of protective immunity induced by this vaccine approach. we investigated the ability of cd8(+) t lymphocytes from rhesus macaques immunized with the live, attenuated siv strain sivmac239deltanef or sivmac239delta3 to inhibit siv replication. cd8(+) t lymphocytes from immunized animals were able to potently suppress siv replication in autologous siv-infected cd ...19989658070
intestinal intraepithelial lymphocytes are primed for gamma interferon and mip-1beta expression and display antiviral cytotoxic activity despite severe cd4(+) t-cell depletion in primary simian immunodeficiency virus infection.intraepithelial lymphocytes (iel) are a critical effector component of the gut-associated lymphoid tissue (galt) and play an important role in mucosal immunity as well as in the maintenance of the epithelial cell integrity and barrier function. the objective of this study was to determine whether simian immunodeficiency virus (siv) infection of rhesus macaques would cause alterations in the immunophenotypic profiles of iel and their mitogen-specific cytokine (gamma interferon [ifn-gamma] and mip ...19989658083
gastrointestinal t lymphocytes retain high potential for cytokine responses but have severe cd4(+) t-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes.gastrointestinal complications in human immunodeficiency virus (hiv) infection are indicative of impaired intestinal mucosal immune system. we used simian immunodeficiency virus (siv)-infected rhesus macaques as an animal model for hiv to determine pathogenic effects of siv on intestinal t lymphocytes. intestinal cd4(+) t-cell depletion and the potential for cytokine responses were examined during siv infection and compared with results for lymphocytes from lymph nodes and blood. flow cytometric ...19989658111
neutralizing antibodies in sera from macaques immunized with attenuated simian immunodeficiency virus.infection with attenuated simian immunodeficiency virus (siv) in rhesus macaques has been shown to raise antibodies capable of neutralizing an animal challenge stock of primary sivmac251 in cemx174 cells that correlate with resistance to infection after experimental challenge with this virulent virus (m. s. wyand, k. h. manson, m. garcia-moll, d. c. montefiori, and r. c. desrosiers, j. virol. 70:3724-3733, 1996). here we show that these neutralizing antibodies are not detected in human and rhesu ...19989658152
two doses of pmpa protect newborn macaques against oral simian immunodeficiency virus infection.simple and affordable intervention strategies are needed to reduce the rate of hiv transmission from mother to infant in developing countries. simian immunodeficiency virus (siv) infection of newborn rhesus macaques is considered to be a useful model of human pediatric hiv infection.19989662190
localization of persistent enterocytozoon bieneusi infection in normal rhesus macaques (macaca mulatta) to the hepatobiliary tree.enterocytozoon bieneusi is the most common microsporidian parasite recognized in human patients with aids. recently, we identified a virtually identical organism causing a spontaneous infection associated with hepatobiliary and intestinal disease in simian immunodeficiency virus (siv)-infected macaques. to examine the natural history of the infection, we examined captive rhesus macaques for e. bieneusi by pcr, in situ hybridization, and cytochemical techniques. pcr performed on fecal dna detecte ...19989666017
specificity of helper t-cells generated from macaques infected with attenuated simian immunodeficiency virus.deletion of the simian immunodeficiency virus (siv) nef gene leads to an attenuated virus phenotype in vivo. we have previously shown that these viruses induce a potent cellular immune response in macaques. to extend these studies, we established virus-specific short-term t-cell lines from four rhesus macaques infected with a nef deletion mutant of siv. these t-cell lines proliferated upon restimulation with whole siv or siv gp140 antigen in vitro. the proliferating cells were characterized as c ...19989680145
different evolution of simian immunodeficiency virus in a natural host and a new host.to address the mechanisms of host-virus adaptation and pathogenesis of lentiviral infections, we compared the evolution of the same isolate of simian immunodeficiency virus (sivsmm9) in two different situations: nonpathogenic infection of its natural host, the sooty mangabey, and aids-inducing infection of a new host, the rhesus macaque. samples were obtained at 6, 12, and 23 or 30 months postinfection from three animals of each species. sequences were derived from the v1 and v2 domains of the s ...19989683570
elevated serum level of soluble cd23 precedes development of b-non-hodgkin's lymphoma in siv-infected rhesus monkeys.patients with hiv infection are at high risk for the development of high-grade b-non-hodgkin's lymphoma (b-nhl). the aim of this study was identification of a predictive diagnostic marker for hiv-associated b-cell lymphomas, using simian-immunodeficiency-virus (siv)-infected rhesus monkeys as a well-established in vivo model of hiv-associated lymphomagenesis. we infected 26 monkeys (macaca mulatta) with sivmax and measured serum levels of scd23 longitudinally until necropsy. of the 26 monkeys, 9 ...19989688307
shortening of the symptom-free period in rhesus macaques is associated with decreasing nonsynonymous variation in the env variable regions of simian immunodeficiency virus sivsm during passage.during six blood passages of simian immunodeficiency virus sivsm in rhesus macaques, the asymptomatic period shortened from 18 months to 1 month. to study sivsm envelope gene (env) evolution during passage in rhesus macaques, the c1 to cd4 binding regions of multiple clones were sequenced at seroconversion and again at death. the env variation found during adaptation was almost completely confined to the variable regions. intrasample sequence variation among clones at seroconversion was lower th ...19989696846
temporal analyses of virus replication, immune responses, and efficacy in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine.despite evidence that live, attenuated simian immunodeficiency virus (siv) vaccines can elicit potent protection against pathogenic siv infection, detailed information on the replication kinetics of attenuated siv in vivo is lacking. in this study, we measured siv rna in the plasma of 16 adult rhesus macaques immunized with a live, attenuated strain of siv (sivmac239deltanef). to evaluate the relationship between replication of the vaccine virus and the onset of protection, four animals per grou ...19989696847
parallel evolution of ccr5-null phenotypes in humans and in a natural host of simian immunodeficiency virus.the c-c chemokine receptor ccr5 in humans and rhesus macaques (macaca mulatta) serves as the primary coreceptor for cellular entry by macrophagetropic strains of human immunodeficiency virus type 1 (hiv-1) and all reported strains of simian immunodeficiency virus (siv) [1-6]. humans homozygous for a 32 bp deletion allele of ccr5, resulting in a null phenotype, are highly resistant to infection by hiv-1 [7-9], prompting development of therapies and vaccines targeting ccr5. we now report a novel d ...19989707408
recombinant modified vaccinia virus ankara-simian immunodeficiency virus gag pol elicits cytotoxic t lymphocytes in rhesus monkeys detected by a major histocompatibility complex class i/peptide tetramer.the utility of modified vaccinia virus ankara (mva) as a vector for eliciting aids virus-specific cytotoxic t lymphocytes (ctl) was explored in the simian immunodeficiency virus (siv)/rhesus monkey model. after two intramuscular immunizations with recombinant mva-sivsm gag pol, the monkeys developed a gag epitope-specific ctl response readily detected in peripheral blood lymphocytes by using a functional killing assay. moreover, those immunizations also elicited a population of cd8+ t lymphocyte ...19989707609
identification of sv40 in brain, kidney and urine of healthy and siv-infected rhesus monkeys.recent reports of simian virus 40 (sv40) sequences in human tumors have prompted investigations into the poorly understood association of this polyomavirus with its primate host, the rhesus monkey (macaca mulatta). in the present study we have used pcr to analyze tissues from 20 monkeys for the presence of sv40. five of the animals, which were infected with simian immunodeficiency virus (siv), were found to exhibit sv40-induced lesions and to have sv40 sequences present in their kidney and brain ...19989718131
env-independent protection induced by live, attenuated simian immunodeficiency virus vaccines.live attenuated simian immunodeficiency viruses (siv), such as nef deletion mutants, are the most effective vaccines tested in the siv-macaque model so far. to modulate the antiviral immune response induced by live attenuated siv vaccines, we had previously infected rhesus monkeys with a nef deletion mutant of siv expressing interleukin 2 (siv-il2) (b. r. gundlach, h. linhart, u. dittmer, s. sopper, s. reiprich, d. fuchs, b. fleckenstein, g. hunsmann, s. stahl-hennig, and k. uberla, j. virol. 71 ...19989733821
longitudinal analysis of behavioral, neurophysiological, viral and immunological effects of siv infection in rhesus monkeys.a model is proposed in which a neurovirulent, microglial-passaged, simian immunodeficiency virus (siv) is used to produce central nervous system (cns) pathology and behavioral deficits in rhesus monkeys reminiscent of those seen in humans infected with human immunodeficiency virus (hiv). the time course of disease progression was characterized by using functional measures of cognition and motor skill, as well as neurophysiologic monitoring. concomitant assessment of immunological and virological ...19989747951
rhesus macaques infected with macrophage-tropic simian immunodeficiency virus (sivmacr71/17e) exhibit extensive focal segmental and global glomerulosclerosis.we previously showed that inoculation of rhesus macaques with molecularly cloned lymphocytetropic simian immunodeficiency virus (sivmac239) results in siv-associated nephropathy (sivan) and that the glomerulosclerotic lesions were associated with the selection of macrophagetropic (m-tropic) variants (v. h. gattone et al., aids res. hum. retroviruses 14:1163-1180, 1998). in the present study, seven rhesus macaques were inoculated with m-tropic sivmacr71/17e, and the renal pathology was examined a ...19989765427
isolation and characterization of a neuropathogenic simian immunodeficiency virus derived from a sooty mangabey.transfusion of blood from a simian immunodeficiency virus (siv)- and simian t-cell lymphotropic virus-infected sooty mangabey (designated fgb) to rhesus and pig-tailed macaques resulted in the development of neurologic disease in addition to aids. to investigate the role of siv in neurologic disease, virus was isolated from a lymph node of a pig-tailed macaque (designated pgm) and the cerebrospinal fluid of a rhesus macaque (designated ron2) and passaged to additional macaques. siv-related neuro ...19989765429
determinants of disease in the simian immunodeficiency virus-infected rhesus macaque: characterizing animals with low antibody responses and rapid progression.clinical and laboratory markers of simian immunodeficiency virus (siv) infection were studied during the first 3 months after intravenous inoculation of rhesus macaques. virus-binding serum antibody titres were correlated strongly with disease progression (p < 0.005) and were predictive of disease outcome by 7 weeks after inoculation. low virus-binding serum antibody responses to siv occurred in animals that also showed acute depletion of circulating cd20+ b cells. acute damage to the cd4+ t cel ...19989780052
molecular cloning and expression of rhesus macaque and sooty mangabey interleukin 16: biologic activity and effect on simian immunodeficiency virus infection and/or replication.interleukin 16 (il-16) has been shown to diminish hiv and siv replication through inhibition of hiv and siv mrna transcription. to evaluate its role further, we compared il-16 cloned from disease-susceptible rhesus macaques and disease-resistant sooty mangabeys. recombinant rhesus macaque (rr) il-16 was compared with recombinant sooty mangabey (rm), human, and other nonhuman primate il-16 sequences and evaluated for its ability to induce chemotaxis and inhibit the mixed lymphocyte response (mlr) ...19989788673
experimental leprosy in rhesus monkeys: transmission, susceptibility, clinical and immunological findings.a total of 46 rhesus monkeys (rm) was inoculated with mycobacterium leprae (ml) and followed clinically and immunologically for extended periods. twenty-one (45.7%) of the rm developed leprosy spanning the known leprosy spectrum, with six of 21 (28.6%) having disease in the borderline lepromatous to lepromatous area of the spectrum. rm with paucibacillary forms of leprosy produced predominantly igg anti-phenolic glycolipid (pgl-i) antibodies and positive lepromin skin test and/or in vitro blasto ...19989805879
homing of mononuclear cells from iliac lymph nodes to the genital and rectal mucosa in non-human primates.the route of immunization may affect the type of immunity that is induced. the objectives of this investigation were to establish in the non-human primate if the internal iliac lymph nodes (ln) function as an inductive site of immunity from which mononuclear cells home to the rectal and cervico-vaginal mucosa. rhesus macaques were immunized with simian immunodeficiency virus (siv) core antigen p27 in the proximity of the iliac lymph nodes, and compared with the intramuscular (i.m.) (deltoid or g ...19989808175
diverse host responses and outcomes following simian immunodeficiency virus sivmac239 infection in sooty mangabeys and rhesus macaques.sooty mangabeys naturally infected with simian immunodeficiency virus (siv) do not develop immunodeficiency despite the presence of viral loads of 10(5) to 10(7) rna copies/ml. to investigate the basis of apathogenic siv infection in sooty mangabeys, three sooty mangabeys and three rhesus macaques were inoculated intravenously with sivmac239 and evaluated longitudinally for 1 year. sivmac239 infection of sooty mangabeys resulted in 2- to 4-log-lower viral loads than in macaques and did not repro ...19989811693
occult systemic infection and persistent simian immunodeficiency virus (siv)-specific cd4(+)-t-cell proliferative responses in rhesus macaques that were transiently viremic after intravaginal inoculation of siv.the intact cervicovaginal mucosa is a relative barrier to the sexual transmission of human immunodeficiency virus type 1 (hiv-1). in the simian immunodeficiency virus (siv) macaque model of hiv infection, seronegative transient viremia (stv; virus isolation positive followed by repeated negative cultures) occurs after intravaginal inoculation of a low dose of pathogenic sivmac251 (c. j. miller, m. marthas, j. torten, n. alexander, j. moore, g. doncel, and a. hendrickx, j. virol. 68:6391-6400, 19 ...19989811741
a pathogenic threshold of virus load defined in simian immunodeficiency virus- or simian-human immunodeficiency virus-infected macaques.to determine if a specific pathogenic threshold of plasma viral rna could be defined irrespective of virus strain, rna levels in the plasma of more than 50 infected rhesus macaques (macaca mulatta) were measured. animals were inoculated intravenously with either simian immunodeficiency virus (siv) or simian-human immunodeficiency virus (shiv) strains of known pathogenic potential (siv8980, sivsmm-3, sivmac32h/j5, sivmac32h/1xc, reverse transcriptase-shiv, shiv89.6p) or with attenuated strains (s ...19989811776
a novel kinase activity associated with nef derived from neurovirulent simian immunodeficiency virus.the nef proteins of simian immunodeficiency virus (siv) and human immunodeficiency virus (hiv) have been shown to associate with several cellular kinases. further, the ability of sivmac239 nef to associate with a p21-activated kinase (pak)-related kinase has been correlated with pathogenic progression to aids in rhesus macaques. because the ability of nef to associate with the pak-related kinase is viral isolate dependent, we reasoned that viral isolates derived from distinct physiological locat ...19989813212
acute fulminant sarcocystosis in a captive-born rhesus macaque.a captive-born juvenile female rhesus macaque (macaca mulatta) was acquired from a commercial breeder and placed in quarantine. within 8 days of arrival, the animal became anorexic, inactive, and dehydrated. subsequently, generalized edema and facial ecchymoses developed, and despite supportive therapy, the animal became moribund and was euthanatized. macroscopic examination showed diffuse stippling and streaking of the myocardium. histopathologic examination revealed multifocal to coalescing my ...19989823591
nasal immunization of nonhuman primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces th1/th2 help for virus-specific immune responses in reproductive tissues.female rhesus macaques were nasally immunized with p55gag (p55) of siv and cholera toxin as a mucosal adjuvant. nasal immunization induced ag-specific iga and igg abs in mucosal secretions (e.g., cervicovaginal secretions, rectal washes, and saliva) and serum. furthermore, high numbers of p55-specific iga and igg ab-forming cells were induced in mucosal effector sites, i.e., uterine cervix, intestinal lamina propria, and nasal passage. p55-specific cd4+ t cells in both systemic and mucosal compa ...19989834076
induction of th2 cytokine expression for p27-specific iga b cell responses after targeted lymph node immunization with simian immunodeficiency virus antigens in rhesus macaques.to determine if there is an association between the isotype of simian immunodeficiency virus (siv)-specific b cell responses and the profile of th1 and th2 cytokine expression, rhesus macaques were immunized with siv antigens via the iliac lymph nodes, using a targeted lymph node (tln) immunization procedure. when cd4+ t cells purified from antigen-stimulated peripheral blood mononuclear cells were analyzed, the levels of th2 cytokine production were gradually increased after the second and thir ...19989419166
tracking members of the simian immunodeficiency virus deltab670 quasispecies population in vivo at single-cell resolution.genetically distinct lentiviruses constitute a quasispecies population that can evolve in response to selective forces. to move beyond characterization of the population as a whole to the behavior of individual members, we devised an in situ hybridization approach that uses genotype-specific probes. we used probes that detect simian immunodeficiency viruses (siv) that differ in sequence in the v1 region of the surface envelope glycoprotein (env) gene to investigate the replication and cellular t ...19989420206
evolution of a simian immunodeficiency virus pathogen.analysis of disease induction by simian immunodeficiency viruses (siv) in macaques was initially hampered by a lack of molecularly defined pathogenic strains. the first molecularly cloned siv strains inoculated into macaques, sivmacbk28 and sivmacbk44 (hereafter designated bk28 and bk44, respectively), were cases in point, since they failed to induce disease within 1 year postinoculation in any inoculated animal. here we report the natural history of infection with bk28 and bk44 in inoculated rh ...19989420239
changes in neuron size in cynomolgus macaques infected with various immunodeficiency viruses and poliovirus.human immunodeficiency virus (hiv) infection leads to clinically significant neuronal pathology, but the underlying mechanism remains unclear. infection of rhesus macaques with the simian immunodeficiency virus sivmac251 has been shown to cause atrophy of hippocampal pyramidal cells. the aim of the current investigation was to determine whether sivmac251 and other viruses with differing abilities to cause immune suppression or encephalitis could cause neuronal atrophy in cynomolgus macaques. ani ...19989888157
localization of simian immunodeficiency virus-infected cells in the genital tract of male and female rhesus macaques.the siv/rhesus macaque model of hiv transmission has led to an increased understanding of the interactions between virus and host during the sexual transmission of hiv. siv can be transmitted across the intact mucosa (stratified squamous epithelium) of the foreskin and glans of the penis of rhesus macaques. siv-infected cells can be found at all levels of the male rhesus macaque reproductive tract and siv can infect cells in the mucosal epithelium of the foreskin of the penis. siv can be transmi ...199810213321
identification of highly attenuated mutants of simian immunodeficiency virus.deletion mutants of the pathogenic clone of simian immunodeficiency virus isolate 239 (sivmac239) were derived that are missing nef, vpr, and upstream sequences (us) in the u3 region of the ltr (sivmac239 delta3), nef, vpx, and us (sivmac239 delta3x), and nef, vpr, vpx, and us (sivmac239 delta4). these multiply deleted derivatives replicated well in the continuously growing cemx174 cell line and were infectious for rhesus monkeys. however, on the basis of virus load measurements, strength of ant ...19989445045
prechallenge high neutralizing antibodies and long-lasting immune reactivity to gp41 correlate with protection of rhesus monkeys against productive simian immunodeficiency virus infection or disease development.to investigate the protective efficacy of various gp130 vaccine preparations, rhesus monkeys were immunized with gp130 oligomers (o-gp130) or two different gp130-monomer preparations (m1-gp130; m2-gp130) and challenged with 50 mid50 of simian immunodeficiency virus (siv)mac32h. following challenge the control animals and all animals of the m1- and m2-gp130 group and 1 animal of the o-gp130 group were productively infected, whereas 3 animals of the o-gp130 group resisted the productive virus repl ...19989859957
importance of the intracytoplasmic domain of the simian immunodeficiency virus (siv) envelope glycoprotein for pathogenesis.sivmac1a11 and sivmac239 are nonpathogenic and pathogenic molecular clones in rhesus macaques, respectively. although these viruses exhibit approximately 98% nucleotide and amino acid sequence homology, differences are found in the length of the translation frames for several genes. sivmac239 has a premature stop codon in nef, whereas sivmac1a11 has a premature stop codon in vpr and two premature stop codons in the intracytoplasmic domain of the env-transmembrane (tm) subunit. recombinant viruse ...19989875311
antiviral effects of 6-chloro-2',3'-dideoxyguanosine in rhesus monkeys acutely infected with simian immunodeficiency virus.a lipophilic dideoxynucleoside analogue, 6-chloro-2',3'-dideoxyguanosine (6-cl-ddg), was expected to be effective against aids-related dementia. in this study, we tested the effect of 6-cl-ddg on simian immunodeficiency virus (sivmac239) replication in vitro and on acute infection of six rhesus monkeys (macaca mulatta) with sivmac239. this compound inhibited siv-induced cytopathic effect in cem x 174 cells and siv replication in vitro with an ed50 value of 2.5 microm. a dose of 25 mg/kg 6-cl-ddg ...19989875380
use of lectins in affinity purification of hiv and siv envelope glycoproteins.the human immunodeficiency viruses (hiv-1 and hiv-2) are the etiologic agents of the acquired immunodeficiency syndrome (aids) and related disorders (1-3) simian immunodeficiency virus(siv) is the corresponding virus for nonhuman primates. sivmac has been isolated from rhesus monkeys (macaca mulatta) with immunosuppression and malignant lymphomas (4).199821374468
morphologic and immunophenotypic characteristics of malignant lymphomas in siv-infected rhesus macaques.eight cases of extranodal non-hodgkin's lymphoma in simian immunodeficiency virus (siv)-infected rhesus macaques, aged 4-9 years, were phenotypically and immunologically characterized, using the updated kiel classification, in order to determine both the differences and the similarities between these types of lymphoma in immunodeficient rhesus macaques (macaca mulatta) and man. the high-grade malignant tumors were of b-cell origin, with a predilection for extranodal growth in viscera and periorb ...199910733204
liver immunity and glutathione.redox processes have been implicated in various biologic processes, including signal transduction, gene expression, and cell proliferation, and several molecules have been identified as redox regulators in cell activation. glutathione is the oldest and most investigated molecule among them. although details of the mechanisms by which glutathione regulates various aspects of cell biology remains to be characterized, the relationship between immunodeficiency and cellular glutathione status is well ...199911228752
comparative analysis of cytotoxic t lymphocytes in lymph nodes and peripheral blood of simian immunodeficiency virus-infected rhesus monkeys.most studies of human immunodeficiency virus type 1 (hiv-1)-specific cytotoxic t lymphocytes (ctl) have been confined to the evaluation of these effector cells in the peripheral blood. what has not been clear is the extent to which ctl activity in the blood actually reflects this effector cell function in the lymph nodes, the major sites of hiv-1 replication. to determine the concordance between ctl activity in lymph nodes and peripheral blood lymphocytes (pbl), ctl specific for simian immunodef ...19999882363
recombinant human cd40 ligand inhibits simian immunodeficiency virus replication: a role for interleukin- 16.cd40 ligand (cd40l), expressed on activated t cells, binds its receptor, cd40, on dendritic cells, b cells, and monocytes/ macrophages. human immunodeficiency virus (hiv)-infected individuals exhibit normal b-cell cd40 expression but diminished expression of cd40l on cd4 + t cells. thus, we studied recombinant human cd40l (hucd40l) in an in vitro rhesus macaque model of acquired immunodeficiency syndrome (aids). hucd40l induced peripheral blood mononuclear cell (pbmc) proliferation independent o ...199910593485
an anti-hiv strategy combining chemotherapy and therapeutic vaccination.combination chemotherapy using potent anti-retroviral agents has led to significant advances in the clinical management of human immunodeficiency virus (hiv) disease. however, the emergence of multiple drug-resistant mutants, the high need for compliance to adhere to demanding drug-dosing schemes, and the remaining toxic side-effects of drugs make the perspective of life-long treatment unattractive and possibly unrealistic. therefore, means must be sought to shorten the time span during which tr ...199910593486
siv/hiv nef recombinant virus (shivnef) produces simian aids in rhesus macaques.the simian immunodeficiency virus (siv) nef gene is an important determinant of viral load and acquired immunodeficiency syndrome (aids) in macaques. a role(s) for the hiv-1 nef gene in infection and pathogenesis was investigated by constructing recombinant viruses in which the nef gene of the pathogenic molecular clone sivmac239 nef was replaced with either hiv-1sf2nef or hiv-1sf33nef. these chimeras, designated shiv-2nef and shiv-33nef, expressed hiv-1 nef protein and replicated efficiently in ...199910600596
rapid clearance of simian immunodeficiency virus particles from plasma of rhesus macaques.perturbation of the equilibrium between human immunodeficiency virus type 1 (hiv-1) and the infected host by administering antiretroviral agents has revealed the rapid turnover of both viral particles and productively infected cells. in this study, we used the infusion of simian immunodeficiency virus (siv) particles into rhesus macaques to obtain a more accurate estimate of viral clearance in vivo. consistently, exogenously infused virions were cleared from plasma with an extremely short half-l ...19999847402
accumulation of mac387+ macrophages in paracortical areas of lymph nodes in rhesus monkeys acutely infected with simian immunodeficiency virus.we investigated the histological features of lymph nodes, focusing on monocytes/macrophages, in rhesus monkeys (macaca mulatta) acutely infected with simian immunodeficiency virus (siv). in monkeys infected with a pathogenic siv, sivmac239, mac387(+) newly blood-derived macrophages markedly increased in number at paracortical areas at 11 to 14 days postinoculation, concomitant with the peak of the primary siv antigenemia. the mac387(+) macrophages densely gathered around high endothelial venules ...199910617929
effect of weekly adefovir (pmea) infusions on hiv-1 virus load: results of a phase i/ii study.the compound 9-(2-phosphonylmethoxyethyl)adenine (adefovir; pmea) is a potent inhibitor of a number of viruses in vitro, such as human immunodeficiency virus (hiv) type 1 and 2, herpes simplex virus (hsv) type 1 and 2, human papillomavirus virus (hbv) and epstein-barr virus (ebv). adefovir also proved to be effective in vivo against feline immunodeficiency virus (fiv) in cats and simian immunodeficiency virus (siv) in rhesus monkeys. in an open, non-placebo-controlled trial the antiviral activit ...199910682155
rapid mucosal cd4(+) t-cell depletion and enteropathy in simian immunodeficiency virus-infected rhesus macaques.human immunodeficiency virus (hiv) infection leads to severe immunologic and functional disturbances in the intestinal tract in late stages of the disease. information on mucosal pathology directly after infection is limited. we characterized this early phase in rhesus macaques infected with simian immunodeficiency virus (siv). methods: eight rhesus macaques were infected with siv. upper endoscopy was performed at defined times before and after infection. viral load, percentage of cd4(+) t cells ...199910220503
simple and choice reaction time performance in siv-infected rhesus macaques.it is well established that hiv infection can lead to motor/cognitive disorders in humans. a number of studies have shown that simian immunodeficiency virus (siv) infection in rhesus macaques parallels many aspects of hiv disease in humans. the purpose of this study was to define further the siv-infected rhesus macaque as a model of neuro-aids. our objective was to detect movement-related impairments in behaviorally trained, siv-infected macaques using both simple and choice reaction time tasks. ...199910221534
emergence of ctl coincides with clearance of virus during primary simian immunodeficiency virus infection in rhesus monkeys.the ctl response was characterized during primary siv/macaque (sivmac) infection of rhesus monkeys to assess its role in containing early viral replication using both an epitope-specific functional and an mhc class i/peptide tetramer-binding assay. the rapid expansion of a single dominant viral epitope-specific ctl population to 1.3-8.3% of circulating cd8+ peripheral blood and 0. 3-1.3% of lymph node cd8+ t cells was observed, peaking at day 13 following infection. a subsequent decrease in numb ...199910227983
simian immunodeficiency virus disease course is predicted by the extent of virus replication during primary infection.to elucidate the relationship between early viral infection events and immunodeficiency virus disease progression, quantitative-competitive and branched-dna methods of simian immunodeficiency virus (siv) rna quantitation were cross-validated and used to measure viremia following infection of rhesus macaques with the pathogenic sivmac251 virus isolate. excellent correlation between the methods suggests that both accurately approximate siv copy number. plasma viremia was evident 4 days postinfecti ...199910233944
highly attenuated vaccine strains of simian immunodeficiency virus protect against vaginal challenge: inverse relationship of degree of protection with level of attenuation.three different deletion mutants of simian immunodeficiency virus (siv) that vary in their levels of attenuation were tested for the ability to protect against mucosal challenge with pathogenic siv. four female rhesus monkeys were vaccinated by intravenous inoculation with sivmac239delta3, four with sivmac239delta3x, and four with sivmac239delta4. these three vaccine strains exhibit increasing levels of attenuation: delta3 < delta3x <delta4. the vaccinated monkeys were challenged by vaginal expo ...199910233957
major histocompatibility complex class i genes in primates: co-evolution with pathogens.the major histocompatibility complex (mhc) is the most polymorphic genetic system known, playing a central role in the cellular immune response to pathogens. the relationship between the mhc of humans and non-human primates has increased our understanding of mhc evolution and how polymorphism of this gene family may have been generated. we will review mhc class i evolution in great apes and old world and new world primates and discuss new data from the simian immunodeficiency virus/rhesus monkey ...199910319271
improved mg2+-based reverse transcriptase assay for detection of primate retroviruses.the reverse transcriptase (rt) assay is a simple, relatively inexpensive, widely used assay that can detect all retroviruses (known and novel retroviruses as well as infectious and defective retroviruses) on the basis of the divalent cation requirement of their rt enzyme, i.e., mg2+ or mn2+. descriptions of various rt assays have been published; however, they cannot be directly applied to the analysis of biological products or clinical samples without further standardization to determine the low ...199910325311
a case of intestinal mycobacterium simiae infection in an siv-infected immunosuppressed rhesus monkey.although mycobacterium simiae was identified and classified more than three decades ago, only a few cases are mentioned in the current literature. after experimental simian immunodeficiency virus infection, a 9-year-old female rhesus monkey (macaca mulatta) developed progressive immunosuppression and gastrointestinal disease very similar to the clinical and pathomorphologic features of johne's disease, which is caused by m. paratuberculosis. acid-fast-positive bacteria reacted immunohistochemica ...199910332833
detection of siv dna in rhesus macaque polymorphonuclear neutrophils.the extent of infection of monkey polymorphonuclear neutrophils (pmn) by simian immunodeficiency virus (siv) has not yet been determined. using the polymerase chain reaction (pcr) technique, we detected the presence of sivmac239 dna in rhesus macaque-derived pmn after 24 hrs of in vitro incubation of the cells with sivmac239. infection by sivmac239 also down-regulated the expression of the bcl-2 apoptosis-blocking gene in the infected pmn. these sivmac239-induced pmn intracellular alterations we ...199910363177
use of major histocompatibility complex class i/peptide/beta2m tetramers to quantitate cd8(+) cytotoxic t lymphocytes specific for dominant and nondominant viral epitopes in simian-human immunodeficiency virus-infected rhesus monkeys.to evaluate the impact of the diversity of antigen recognition by t lymphocytes on disease pathogenesis, we must be able to identify and analyze simultaneously cytotoxic t-lymphocyte (ctl) responses specific for multiple viral epitopes. many of the studies of the role of cd8(+) ctls in aids pathogenesis have been done with simian immunodeficiency virus (siv)- and simian-human immunodeficiency virus (shiv)-infected rhesus monkeys. these studies have frequently made use of the well-defined siv gag ...199910364294
induction of aids in rhesus monkeys by a recombinant simian immunodeficiency virus expressing nef of human immunodeficiency virus type 1.a nef gene is present in all primate lentiviruses, including human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus of macaque monkeys (sivmac). however, the nef genes of hiv-1 and sivmac exhibit minimal sequence identity, and not all properties are shared by the two. nef sequences of sivmac239 were replaced by four independent nef alleles of hiv-1 in a context that was optimal for expression. the sources of the hiv-1 nef sequences included nl 4-3, a variant nl 4-3 gene de ...199910364333
persistent infection of rhesus macaques by the rev-independent nef(-) simian immunodeficiency virus sivmac239: replication kinetics and genomic stability.we generated previously a nef(-), replication-competent clone of sivmac239 in which the rev protein and the rev-responsive element were replaced by the constitutive transport element (cte) of simian retrovirus type 1 (a. s. von gegerfelt and b. k. felber, virology 232:291-299, 1997). in the present report, we show that this virus was able to infect and replicate in rhesus macaques. the rev-independent nef(-) simian immunodeficiency virus induced a persistent humoral immune response in all monkey ...199910364376
alterations in rantes gene expression and t-cell prevalence in intestinal mucosa during pathogenic or nonpathogenic simian immunodeficiency virus infection.rantes, a beta-chemokine, can suppress human immunodeficiency virus (hiv) as well as simian immunodeficiency virus (siv) infections in t-lymphocyte cultures in vitro. however, the association of rantes levels in peripheral blood with viral loads and disease outcome in hiv infection has been inconclusive. siv-infected rhesus macaques were evaluated to determine whether rantes gene expression correlated with suppression of viral infection in intestinal lymphoid tissues. intestinal tissues were obt ...199910364494
ethanol suppression of the functional state of polymorphonuclear leukocytes obtained from uninfected and simian immunodeficiency virus infected rhesus macaques.human immunodeficiency virus (hiv) infection and alcohol abuse frequently coexist in the host and are known to suppress individually the host response to a variety of opportunistic infections.199910371409
the relationship of personality dimensions in adult male rhesus macaques to progression of simian immunodeficiency virus disease.studies of nonhuman primate personality have suggested that physiological correlates of relevant behavioral dimensions exist. the present study examined personality using techniques similar to those employed in human personality research. adult male rhesus monkeys were each rated on 25 adjectives while living in their natal groups. approximately 1.5 years later, 18 animals were inoculated with the simian immunodeficiency virus (siv) and exposed to socially stable or socially unstable conditions. ...199910373278
activated memory cd4(+) t helper cells repopulate the intestine early following antiretroviral therapy of simian immunodeficiency virus-infected rhesus macaques but exhibit a decreased potential to produce interleukin-2.using the simian immunodeficiency virus (siv)-infected rhesus macaque model, we performed a longitudinal study to determine the effect of antiretroviral therapy on the phenotype and functional potential of cd4(+) t cells repopulating intestinal mucosa in human immunodeficiency virus infection. severe depletion of cd4(+) and cd4(+) cd8(+) t cells occurred in the intestinal mucosa during primary siv infection. the majority of these cells were of activated memory phenotype. phosphonate 9-[2-(phosph ...199910400763
isolation and partial characterization of a lentivirus from talapoin monkeys (myopithecus talapoin).we have identified a novel lentivirus prevalent in talapoin monkeys (myopithecus talapoin), extending previous observations of human immunodeficiency virus-1 cross-reactive antibodies in the serum of these monkeys. we obtained a virus isolate from one of three seropositive monkeys initially available to us. the virus was tentatively named simian immunodeficiency virus from talapoin monkeys (sivtal). despite the difficulty of isolating this virus, it was readily passed between monkeys in captivit ...199910405363
increased expression of nitric oxide synthase and dendritic injury in simian immunodeficiency virus encephalitis.widespread dendritic injury may be one mechanism involved in the neurologic impairment that occurs in hiv-1 infection. the objectives of this study were to quantitate the extent of dendritic injury in a primate model of central nervous system (cns) infection, investigate the role of nitric oxide (no) as a mediator of neuropathologic changes, and evaluate the relation of these changes to cognitive and motor function.199910413365
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