Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| immune failure in the absence of profound cd4+ t-lymphocyte depletion in simian immunodeficiency virus-infected rapid progressor macaques. | a fraction of simian immunodeficiency virus (siv)-infected macaques develop rapidly progressive disease in the apparent absence of detectable siv-specific antibody responses. to characterize the immunopathogenesis of this syndrome, we studied viral load, cd4+ t-lymphocyte numbers as well as cellular and humoral immune responses to siv and other exogenous antigens in four sivsm-infected rhesus macaques that progressed to aids 9 to 16 weeks postinoculation. each of these animals exhibited high lev ... | 2004 | 14671109 |
| dc-sign from african green monkeys is expressed in lymph nodes and mediates infection in trans of simian immunodeficiency virus sivagm. | african green monkeys (agms) infected by simian immunodeficiency virus (siv) sivagm are resistant to aids. sivagm-infected agms exhibit levels of viremia similar to those described during pathogenic human immunodeficiency virus type 1 (hiv-1) and sivmac infections in humans and macaques, respectively, but contain lower viral loads in their lymph nodes. we addressed the potential role of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (dc-sign; cd209) in viral disse ... | 2004 | 14694112 |
| gamma interferon-mediated inflammation is associated with lack of protection from intravaginal simian immunodeficiency virus sivmac239 challenge in simian-human immunodeficiency virus 89.6-immunized rhesus macaques. | although gamma interferon (ifn-gamma) is a key mediator of antiviral defenses, it is also a mediator of inflammation. as inflammation can drive lentiviral replication, we sought to determine the relationship between ifn-gamma-related host immune responses and challenge virus replication in lymphoid tissues of simian-human immunodeficiency virus 89.6 (shiv89.6)-vaccinated and unvaccinated rhesus macaques 6 months after challenge with simian immunodeficiency virus sivmac239. vaccinated-protected m ... | 2004 | 14694116 |
| magnetic resonance imaging of activated proliferating rhesus macaque t cells labeled with superparamagnetic monocrystalline iron oxide nanoparticles. | imaging of adoptively transferred cells in vivo by magnetic resonance imaging (mri) could provide important information on disease-related patterns of lymphocyte homing in nonhuman primate models of aids. as a preliminary study to assess the feasibility of visualizing activated rhesus t cells by mri, anti-cd3/cd28-expanded cd4+ t lymphocytes were labeled in vitro with monocrystalline iron oxide nanoparticles (mion). intracellular incorporation of mion was determined by transmission electron micr ... | 2004 | 14707787 |
| simian immunodeficiency virus promoter exchange results in a highly attenuated strain that protects against uncloned challenge virus. | among the many simian immunodeficiency virus (siv) immunogens, only live attenuated viral vaccines have afforded strong protection to a natural pathogenic isolate. since the promoter is crucial to the tempo of viral replication in general, it was reasoned that promoter exchange might confer a novel means of attenuating siv. the core enhancer and promoter sequences of the siv macaque 239nefstop strain (nf-kappab/sp1 region from -114 bp to mrna start) have been exchanged for those of the human cyt ... | 2004 | 14722263 |
| dysregulation of the polo-like kinase pathway in cd4+ t cells is characteristic of pathogenic simian immunodeficiency virus infection. | cd4(+) t-cell dysfunction highlighted by defects within the intracellular signaling cascade and cell cycle has long been characterized as a direct and/or indirect consequence of human immunodeficiency virus (hiv) infection in humans and simian immunodeficiency virus (siv) infection in rhesus macaques (rm). dysregulation of the m phase of the cell cycle is a well-documented effect of hiv or siv infection both in vivo and in vitro. in this study the effect of siv infection on the modulation of two ... | 2004 | 14722302 |
| the paradox of simian immunodeficiency virus infection in sooty mangabeys: active viral replication without disease progression. | simian immunodeficiency virus sivsm causes an asymptomatic infection in its natural host, the sooty mangabey, but induces an immunodeficiency syndrome very similar to human aids when transferred to a new host species such as the rhesus macaque. unexpectedly, sivsm replication dynamics is comparable in the two species, with rapid accumulation of viral mutations and a high viral load detected in both mangabeys and macaques. in contrast, clear differences are observed in immune parameters. pathogen ... | 2004 | 14766388 |
| protection against mucosal simian immunodeficiency virus siv(mac251) challenge by using replicating adenovirus-siv multigene vaccine priming and subunit boosting. | whereas several recent aids vaccine strategies have protected rhesus macaques against a pathogenic simian/human immunodeficiency virus (shiv)(89.6p) challenge, similar approaches have provided only modest, transient reductions in viral burden after challenge with virulent, pathogenic siv, which is more representative of hiv infection of people. we show here that priming with replicating adenovirus recombinants encoding siv env/rev, gag, and/or nef genes, followed by boosting with siv gp120 or an ... | 2004 | 14963117 |
| highly uneven distribution of tenofovir-selected simian immunodeficiency virus in different anatomical sites of rhesus macaques. | antiviral tenofovir monotherapy was used to determine whether drug-selected simian immunodeficiency virus (siv) variants replaced their wild-type progenitors at the same rate in different tissues of six rhesus macaques. the relative frequencies of drug-resistant and wild-type genotypes were measured longitudinally in blood and in 23 lymphoid and nonlymphoid tissues collected at necropsy. the mutant/wild-type genotype ratio was measured using a heteroduplex tracking assay targeting tenofovir-sele ... | 2004 | 14963139 |
| early protection against pathogenic virus infection at a mucosal challenge site after vaccination with attenuated simian immunodeficiency virus. | atraumatic application of attenuated sivmac239 delta nef vaccine to the tonsils of rhesus macaques provided protection against challenge 26 weeks later with infectious sivmac251 applied through this route. early events at the mucosal portal of entry of challenge virus were followed. wild-type virus was detected in nonvaccinated controls by day 4, and then simian immunodeficiency virus (siv) replicated vigorously at days 7 and 14. in contrast, a challenge of 10 of 10 vaccinees with siv did not si ... | 2004 | 14970317 |
| efficient gene transfer into rhesus repopulating hematopoietic stem cells using a simian immunodeficiency virus-based lentiviral vector system. | high-titer, hiv-1-based lentiviral vector particles were found to transduce cytokine-mobilized rhesus macaque cd34(+) cells and clonogenic progenitors very poorly (< 1%), reflecting the postentry restriction in rhesus cells to hiv infection. to overcome this barrier, we developed a simian immunodeficiency virus (siv)-based vector system. a single exposure to a low concentration of amphotropic pseudotyped siv vector particles encoding the green fluorescent protein (gfp) resulted in gene transfer ... | 2004 | 14976042 |
| the cytoplasmic body component trim5alpha restricts hiv-1 infection in old world monkeys. | host cell barriers to the early phase of immunodeficiency virus replication explain the current distribution of these viruses among human and non-human primate species. human immunodeficiency virus type 1 (hiv-1), the cause of acquired immunodeficiency syndrome (aids) in humans, efficiently enters the cells of old world monkeys but encounters a block before reverse transcription. this species-specific restriction acts on the incoming hiv-1 capsid and is mediated by a dominant repressive factor. ... | 2004 | 14985764 |
| repeated low-dose mucosal simian immunodeficiency virus sivmac239 challenge results in the same viral and immunological kinetics as high-dose challenge: a model for the evaluation of vaccine efficacy in nonhuman primates. | simian immunodeficiency virus (siv) challenge of rhesus macaques provides a relevant model for the assessment of human immunodeficiency virus (hiv) vaccine strategies. to ensure that all macaques become infected, the vaccinees and controls are exposed to large doses of pathogenic siv. these nonphysiological high-dose challenges may adversely affect vaccine evaluation by overwhelming potentially efficacious vaccine responses. to determine whether a more physiologically relevant low-dose challenge ... | 2004 | 14990733 |
| impaired performance on a rhesus monkey neuropsychological testing battery following simian immunodeficiency virus infection. | infection with simian immunodeficiency virus (siv) in macaques provides an excellent model of aids including hiv-induced central nervous system (cns) pathology and cognitive/behavioral impairment. recently a behavioral test battery has been developed for macaques based on the cantab human neuropsychological testing battery. as with human neuropsychological batteries, different tasks are thought to involve different neural substrates, and therefore performance profiles may assess function in part ... | 2004 | 15000701 |
| amino acid 324 in the simian immunodeficiency virus sivmac v3 loop can confer cd4 independence and modulate the interaction with ccr5 and alternative coreceptors. | the v3 loop of the simian immunodeficiency virus (siv) envelope protein (env) largely determines interactions with viral coreceptors. to define amino acids in v3 that are critical for coreceptor engagement, we functionally characterized env variants with amino acid substitutions at position 324 in v3, which has previously been shown to impact siv cell tropism. these changes modulated ccr5 engagement and, in some cases, allowed the efficient usage of ccr5 in the absence of cd4. the tested amino a ... | 2004 | 15016843 |
| correlation between env v1/v2 region diversification and neutralizing antibodies during primary infection by simian immunodeficiency virus sm in rhesus macaques. | evolution of the domain encoding the v1/v2 variable region of the simian immunodeficiency virus sm (sivsm) envelope (env) gene was analyzed in relation to route of virus challenge, virus load, and neutralizing antibody (nab) titers during primary infection of rhesus macaques with the pathogenic sivsme660 isolate. in this model system animals are initially infected with multiple viruses as evidenced by the presence of multiple v1/v2 genotypic variants that could be resolved by using a heteroduple ... | 2004 | 15016879 |
| highly effective control of an aids virus challenge in macaques by using vesicular stomatitis virus and modified vaccinia virus ankara vaccine vectors in a single-boost protocol. | previous studies have shown that vaccination and boosting of rhesus macaques with attenuated vesicular stomatitis virus (vsv) vectors encoding env and gag proteins of simian immunodeficiency virus-human immunodeficiency virus (shiv) hybrid viruses protect rhesus macaques from aids after challenge with the highly pathogenic shiv 89.6p (23). in the present study, we compared the effectiveness of a single prime-boost protocol consisting of vsv vectors expressing shiv env, gag, and pol proteins to t ... | 2004 | 15047809 |
| a single amino acid substitution in human apobec3g antiretroviral enzyme confers resistance to hiv-1 virion infectivity factor-induced depletion. | hiv-1 and other retroviruses occasionally undergo hypermutation, characterized by a high rate of g-to-a substitution. recently, the human apolipoprotein b mrna-editing, enzyme-catalytic, polypeptide-like 3g (apobec3g), first identified as cem15, was shown to be packaged into retroviral virions and to deaminate deoxycytidine to deoxyuridine in newly synthesized viral minus-strand dna, thereby inducing g-to-a hypermutation. this innate mechanism of resistance to retroviral infection is counteracte ... | 2004 | 15054139 |
| roles of substrate availability and infection of resting and activated cd4+ t cells in transmission and acute simian immunodeficiency virus infection. | in studies of sexual mucosal transmission and early stages of simian immunodeficiency virus (siv) and hiv infections, productive infection predominates in cd4(+) t cell populations, in both ostensibly resting and activated cells. the surprising ability of siv and hiv to replicate in resting cells in vivo, in contrast to propagation of infection in vitro, suggested a model in which during the early stages of infection these viruses exploit the greater availability of resting cells to maintain unb ... | 2004 | 15064398 |
| blockade of t cell costimulation reveals interrelated actions of cd4+ and cd8+ t cells in control of siv replication. | in vivo blockade of cd28 and cd40 t cell costimulation pathways during acute simian immunodeficiency virus (siv) infection of rhesus macaques was performed to assess the relative contributions of cd4+ t cells, cd8+ t cells, and ab responses in modulating siv replication and disease progression. transient administration of ctla4-ig and anti-cd40l mab to siv-infected rhesus macaques resulted in dramatic inhibition of the generation of both siv-specific cellular and humoral immune responses. acute ... | 2004 | 15067316 |
| roles of target cells and virus-specific cellular immunity in primary simian immunodeficiency virus infection. | there is an ongoing debate on whether acute human immunodeficiency virus infection is controlled by target cell limitation or by virus-specific cellular immunity. to resolve this question, we developed a novel mathematical modeling scheme which allows us to incorporate measurements of virus load, target cells, and virus-specific immunity and applied it to a comprehensive data set generated in an experiment involving rhesus macaques infected with simian immunodeficiency virus. half of the macaque ... | 2004 | 15078967 |
| simian immunodeficiency virus infection of hematopoietic stem cells and bone marrow stromal cells. | using a well-characterized fetal rhesus monkey model, simian immunodeficiency virus (siv) infection of hematopoietic stem cells (hscs) and stromal cells was investigated to characterize bone marrow abnormalities in siv-infected animals in vivo. fetuses (n = 4) were inoculated in utero with pathogenic sivmac251 using established techniques at 65 days; gestation (early second trimester), then harvested for tissues 65 days after inoculation (late third trimester), and compared with findings from co ... | 2004 | 15097297 |
| induction of disease by a molecularly cloned highly pathogenic simian immunodeficiency virus/human immunodeficiency virus chimera is multigenic. | one of three full-length infectious molecular clones of shiv(dh12r), designated shiv(dh12r-cl-7) and obtained from productively infected rhesus monkey peripheral blood mononuclear cells, directed rapid and irreversible loss of cd4+ t cells within 3 weeks of its inoculation into indian rhesus monkeys. induction of complete cd4+ t-cell depletion by shiv(dh12r-cl-7) was found to be dependent on inoculum size. the acquisition of this pathogenic phenotype was accompanied by the introduction of 42 ami ... | 2004 | 15113931 |
| passive immunotherapy in simian immunodeficiency virus-infected macaques accelerates the development of neutralizing antibodies. | passively transferred neutralizing antibodies can block lentivirus infection, but their role in postexposure prophylaxis is poorly understood. in this nonhuman-primate study, the effects of short-term antibody therapy on 5-year disease progression, virus load, and host immunity were explored. we reported previously that postinfection passive treatment with polyclonal immune globulin with high neutralizing titers against sivsme660 (sivig) significantly improved the 67-week health of sivsme660-inf ... | 2004 | 15140996 |
| body-composition changes in the simian immunodeficiency virus-infected juvenile rhesus macaque. | body-composition changes are common in individuals infected with human immunodeficiency virus. the purpose of the present study was to measure, as a model of wasting in acquired immunodeficiency syndrome (aids), longitudinal body-composition changes in macaques infected with simian immunodeficiency virus (siv). | 2004 | 15143467 |
| high beta-chemokine expression levels in lymphoid tissues of simian/human immunodeficiency virus 89.6-vaccinated rhesus macaques are associated with uncontrolled replication of simian immunodeficiency virus challenge inoculum. | viral suppression by noncytolytic cd8+ t cells, in addition to that by classic antiviral cd8+ cytotoxic t lymphocytes, has been described for human immunodeficiency virus and simian immunodeficiency virus (siv) infections. however, the role of soluble effector molecules, especially beta-chemokines, in antiviral immunity is still controversial. in an attenuated vaccine model, approximately 60% of animals immunized with simian/human immunodeficiency virus (shiv) 89.6 and then challenged intravagin ... | 2004 | 15163733 |
| in vivo 1h mrs of brain injury and repair during acute siv infection in the macaque model of neuroaids. | the metabolic response of the rhesus macaque brain during acute simian immunodeficiency virus (siv) infection was investigated with in vivo (1)h mr spectroscopy. fifteen rhesus macaques were studied before inoculation, and once or twice after infection. in all, 13/15 macaques had elevations of cho/naa at 11-13 days postinoculation (dpi); all 10 macaques measured after 13 dpi had subsequent reduction of this ratio (anova, p < 10(-6)). there were significant increases in cho/cr (20%, p = 0.04) and ... | 2004 | 15170829 |
| cell-cycle dysregulation in the immunopathogenesis of aids. | for a number of years the pathogenesis of aids was thought to be essentially related to direct human immunodeficiency virus (hiv)-mediated killing of cd4+ t cells. more recently, attention has shifted to pathogenic models that emphasize the role of generalized immune system activation and the excess apoptosis of uninfected t cells in inducing hiv-associated cd4+ t-cell depletion. the main focus of our research is to better define the determinants and the consequences of these "indirect" mechanis ... | 2004 | 15181287 |
| brain virus burden and indoleamine-2,3-dioxygenase expression during lentiviral infection of rhesus monkey are concomitantly lowered by 6-chloro-2',3'-dideoxyguanosine. | increased kynurenine pathway metabolism has been implicated in the aetiology of lentiviral encephalopathy. indoleamine-2,3-dioxygenase (ido) initiates the increased production of kynurenine pathway metabolites like quinolinic acid (quin). quin itself is elevated in aids-diseased monkey and human brain parenchyma and cerebrospinal fluid at levels excitotoxic for neurons in vitro. this study investigates the cellular origin of ido biosynthesis in the brain of rhesus monkeys infected with simian im ... | 2004 | 15182307 |
| dopamine deficits and regulation of the camp second messenger system in brains of simian immunodeficiency virus-infected rhesus monkeys. | the basal ganglia, structures rich in the neurotransmitter dopamine, are primarily affected during human immunodeficiency virus (hiv) infection. the authors measured levels of dopamine and its metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid, in brains of uninfected and simian immunodeficiency virus (siv)-infected rhesus monkeys during the asymptomatic stage of the infection. moreover, the authors investigated changes in cyclic adenosine monophosphate (camp) and camp response el ... | 2004 | 15204921 |
| cytotoxic t lymphocyte-based control of simian immunodeficiency virus replication in a preclinical aids vaccine trial. | recently, encouraging aids vaccine trials in macaques have implicated cytotoxic t lymphocytes (ctls) in the control of the simian human immunodeficiency virus shiv89.6p that induces acute cd4(+) t cell depletion. however, none of these vaccine regimens have been successful in the containment of replication of the pathogenic simian immunodeficiency viruses (sivs) that induce chronic disease progression. indeed, it has remained unclear if vaccine-induced ctl can control siv replication. here, we s ... | 2004 | 15210746 |
| necrotizing meningoencephalitis and pneumonitis in a simian immunodeficiency virus-infected rhesus macaque due to acanthamoeba. | free-living amoebae of the genus acanthamoeba can cause a fatal disease of the brain in humans called granulomatous amoebic encephalitis. we present a case of meningoencephalitis and pneumonitis in a simian immunodeficiency virus (siv)-infected rhesus macaque caused by acanthamoeba sp. the animal became ill 176 days after intravenous inoculation with sivmac251 after a short history of weight loss and a sudden onset of hind limb paresis and abnormal head movements. histopathologic examination of ... | 2004 | 15232140 |
| viral and immunological factors associated with breast milk transmission of siv in rhesus macaques. | the viral and host factors involved in transmission of hiv through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. to evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of simian immunodeficiency virus (siv) in lactating rhesus macaques (macaca mulatta) as a model of natural breast milk transmission of hiv. | 2004 | 15253769 |
| cpg-c immunostimulatory oligodeoxyribonucleotide activation of plasmacytoid dendritic cells in rhesus macaques to augment the activation of ifn-gamma-secreting simian immunodeficiency virus-specific t cells. | there are two principle subsets of dendritic cells (dcs); cd11c(+)cd123(-) myeloid dcs (mdcs) and cd11c(-)cd123(+) plasmacytoid dcs (pdcs). dc activation via tnf-tnfrs (e.g., cd40l) and tlrs (e.g., immunostimulatory oligodeoxyribonucleotides (iss-odns)) is crucial for maximal stimulation of innate and adaptive immunity. macaque dc biology is being studied to improve hiv vaccines using the siv macaque model. using lineage (lin) markers to exclude non-dcs, lin(-)hla-dr(+)cd11c(+)cd123(-) mdcs and ... | 2004 | 15265893 |
| macaque dendritic cells infected with siv-recombinant canarypox ex vivo induce siv-specific immune responses in vivo. | dendritic cells (dcs) infected with recombinant avipox vectors express the introduced genes and activate antigen-specific t cells. dcs exhibit distinct differentiation-dependent immune functions. moreover, immature dcs are readily infected by canarypox vectors, but undergo tumor necrosis factor (tnf)-alpha-dependent death, while fewer mature dcs get infected and resist dying. a pilot study was performed using the rhesus macaque system to explore whether immature and mature dcs infected with siv- ... | 2004 | 15320991 |
| enhanced siv replication and accelerated progression to aids in macaques primed to mount a cd4 t cell response to the siv envelope protein. | given the dual role of cd4 t cells as both immune effectors and targets for hiv infection, the balance of cd4 versus cd8 t cell-mediated responses induced by candidate aids vaccines may be critical in determining postvaccination infection outcomes. an attenuated recombinant varicella-zoster virus vaccine expressing the simian immunodeficiency virus (siv) envelope (env) elicited nonneutralizing env-binding antibodies and little if any cytotoxic t lymphocyte responses in rhesus macaques (macaca mu ... | 2004 | 15326293 |
| efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. | the specificity of nonnucleoside reverse transcriptase (rt) inhibitors (nnrtis) for the rt of human immunodeficiency virus type 1 (hiv-1) has prevented the use of simian immunodeficiency virus (siv) in the study of nnrtis and nnrti-based highly active antiretroviral therapy. however, a siv-hiv-1 chimera (rt-shiv), in which the rt from sivmac239 was replaced with the rt-encoding region from hiv-1, is susceptible to nnrtis and is infectious to rhesus macaques. we have evaluated the antiviral activ ... | 2004 | 15328115 |
| natural and experimental infection of immunocompromised rhesus macaques (macaca mulatta) with the microsporidian enterocytozoon bieneusi genotype d. | microsporidia are obligate intracellular parasites that cause opportunistic infections in aids and other immunocompromised patients. eight simian immunodeficiency virus (siv)-infected rhesus macaque monkeys (macaca mulatta) were inoculated orally with enterocytozoon bieneusi spores isolated from intestinal lavage fluid of an aids patient (genotype d) to study the natural history of this infection. four monkeys were already naturally infected with e. bieneusi (also genotype d), and were included ... | 2004 | 15345231 |
| comprehensive analysis of nef functions selected in simian immunodeficiency virus-infected macaques. | a variety of simian immunodeficiency virus (sivmac) nef mutants have been investigated to clarify which in vitro nef functions contribute to efficient viral replication and pathogenicity in rhesus macaques. most of these nef alleles, however, were only functionally characterized for their ability to down-modulate cd4 and class i major histocompatibility complex (mhc-i) cell surface expression and to enhance siv replication and infectivity. to obtain information on the in vivo relevance of more r ... | 2004 | 15367626 |
| identification of t lymphocytes in simian immunodeficiency virus encephalitis: distribution of cd8+ t cells in association with central nervous system vessels and virus. | t lymphocytes are found within brains infected with human immunodeficiency virus (hiv) or simian immunodeficiency virus (siv) where they are a minor, but consistently identified, population. however, little analysis of their phenotypes has been done, and questions concerning whether or not they are viral antigen specific has not been thoroughly examined. we investigated the central nervous system (cns) of siv-infected rhesus macaques to identify t-lymphocyte subsets in relation to virus-infected ... | 2004 | 15385254 |
| vaccine protection from cd4+ t-cell loss caused by simian immunodeficiency virus (siv) mac251 is afforded by sequential immunization with three unrelated vaccine vectors encoding multiple siv antigens. | candidate human immunodeficiency virus (hiv) vaccine strategies that induce strong cellular immune responses protect rhesus macaques that are infected with recombinant simian/human immunodeficiency virus shiv89.6p from acute cd4+ t-cell loss and delay progression to aids. however, similar strategies have not proven as efficacious in the simian immunodeficiency virus (siv)mac model of aids, an infection that causes a slow, steady loss of cd4+ t-cell function and numbers in rhesus macaques similar ... | 2004 | 15448353 |
| modulation by morphine of viral set point in rhesus macaques infected with simian immunodeficiency virus and simian-human immunodeficiency virus. | six rhesus macaques were adapted to morphine dependence by injecting three doses of morphine (5 mg/kg of body weight) for a total of 20 weeks. these animals along with six control macaques were infected intravenously with mixture of simian-human immunodeficiency virus ku-1b (shiv(ku-1b)), shiv(89.6p), and simian immunodeficiency virus 17e-fr. levels of circulating cd4(+) t cells and viral loads in the plasma and the cerebrospinal fluid were monitored in these macaques for a period of 12 weeks. b ... | 2004 | 15452267 |
| identification of seventeen new simian immunodeficiency virus-derived cd8+ t cell epitopes restricted by the high frequency molecule, mamu-a*02, and potential escape from ctl recognition. | mhc class i-restricted cd8+ t cells play an important role in controlling hiv and siv replication. in siv-infected indian rhesus macaques (macaca mulatta), comprehensive cd8+ t cell epitope identification has only been undertaken for two alleles, mamu-a*01 and mamu-b*17. as a result, these two molecules account for virtually all known mhc class i-restricted siv-derived cd8+ t cell epitopes. siv pathogenesis research and vaccine testing have intensified the demand for epitopes restricted by addit ... | 2004 | 15470050 |
| abrogation of attenuated lentivirus-induced protection in rhesus macaques by administration of depo-provera before intravaginal challenge with simian immunodeficiency virus mac239. | in nonhuman primate models of acquired immunodeficiency syndrome, live attenuated lentiviruses provide the most reliable protection from systemic and mucosal challenge with pathogenic simian immunodeficiency virus (siv). although live attenuated lentiviruses may never be used in humans because of safety concerns, understanding the nature of the protective immune mechanisms induced by live attenuated vaccines in primate models will be useful for developing other vaccine approaches. approximately ... | 2004 | 15478078 |
| a novel approach for producing lentiviruses that are limited to a single cycle of infection. | we have devised a novel approach for producing simian immunodeficiency virus (siv) strains and, potentially, human immunodeficiency virus type 1 (hiv-1) strains that are limited to a single cycle of infection. unlike previous lentiviral vectors, our single-cycle siv is capable of expressing eight of the nine viral gene products and infected cells release immature virus particles that are unable to complete subsequent rounds of infection. single-cycle siv (scsiv) was produced by using a two-plasm ... | 2004 | 15479813 |
| insufficient production and tissue delivery of cd4+ memory t cells in rapidly progressive simian immunodeficiency virus infection. | the mechanisms linking human immunodeficiency virus replication to the progressive immunodeficiency of acquired immune deficiency syndrome are controversial, particularly the relative contribution of cd4+ t cell destruction. here, we used the simian immunodeficiency virus (siv) model to investigate the relationship between systemic cd4+ t cell dynamics and rapid disease progression. of 18 rhesus macaques (rms) infected with ccr5-tropic sivmac239 (n=14) or cxcr4-tropic sivmac155t3 (n=4), 4 of the ... | 2004 | 15545355 |
| distinct genomic integration of mlv and siv vectors in primate hematopoietic stem and progenitor cells. | murine leukemia virus (mlv)-derived vectors are widely used for hematopoietic stem cell (hsc) gene transfer, but lentiviral vectors such as the simian immunodeficiency virus (siv) may allow higher efficiency transfer and better expression. recent studies in cell lines have challenged the notion that retroviruses and retroviral vectors integrate randomly into their host genome. medical applications using these vectors are aimed at hscs, and thus large-scale comprehensive analysis of mlv and siv i ... | 2004 | 15550989 |
| wasting syndrome and disruption of the somatotropic axis in simian immunodeficiency virus-infected macaques with mycobacterium avium complex infection. | mycobacterium avium is a common opportunistic infection of patients with acquired immunodeficiency syndrome (aids). we used the simian immunodeficiency virus (siv)-infected rhesus macaque (macaca mulatta) model to examine whether disseminated m. avium is associated with disruption of the somatotropic axis in aids. macaques were followed prospectively, and body composition was determined by dual-energy x-ray absorption. serum levels of insulin-like growth factor (igf)-1, igf binding protein-3, gr ... | 2004 | 15551219 |
| a period of transient viremia and occult infection precedes persistent viremia and antiviral immune responses during multiple low-dose intravaginal simian immunodeficiency virus inoculations. | in rhesus macaques, classic systemic infection, characterized by persistent viremia and seroconversion, occurred after multiple low-dose (10(3) 50% tissue culture infective doses) intravaginal (ivag) inoculations with simian immunodeficiency virus (siv) strain sivmac251. monkeys developed classic siv infections after a variable number of low-dose ivag exposures to sivmac251. once established, the systemic infection was identical to siv infection following high-dose ivag siv inoculation. however, ... | 2004 | 15564513 |
| acute siv infection of the brain leads to upregulation of il6 and interferon-regulated genes: expression patterns throughout disease progression and impact on neuroaids. | the virus/host interactions during the acute phase of human immunodeficiency virus (hiv) infection help determine the course of disease. during this time period, virus enters the brain. here, we report clusters of genes whose transcripts are significantly upregulated in the frontal lobe of the brain during acute simian immunodeficiency virus (siv) infection of rhesus monkeys. many of these genes are involved in interferon (ifn) and/or interleukin (il)-6 pathways. although neither ifnalpha nor if ... | 2004 | 15579284 |
| elevated interleukin-7 levels not sufficient to maintain t-cell homeostasis during simian immunodeficiency virus-induced disease progression. | elevated levels of interleukin 7 (il-7) have been correlated with various t-cell depletion conditions, including hiv infection, and suggested as an indicator of hiv disease progression (aids and death). here, the assessment of pathogenic simian immunodeficiency virus (sivmac239) infection in rhesus macaques demonstrated a clear association between a significant elevation in il-7 levels and disease progression. in 5 macaques that progressed to simian aids and death, elevated il-7 levels were unab ... | 2004 | 14525780 |
| strong cellular and humoral anti-hiv env immune responses induced by a heterologous rhabdoviral prime-boost approach. | recombinant rhabdovirus vectors expressing human immunodeficiency virus (hiv) and/or simian immunodeficiency virus (siv) proteins have been shown to induce strong immune responses in mice and rhesus macaques. however, the finding that such responses protect rhesus macaques from aids-like disease but not from infection indicates that further improvements for these vectors are needed. here, we designed a prime-boost schedule consisting of a rabies virus (rv) vaccine strain and a recombinant vesicu ... | 2005 | 15582655 |
| impact of thymectomy on the peripheral t cell pool in rhesus macaques before and after infection with simian immunodeficiency virus. | the goal of this study was to define, by surgical removal of the thymus in juvenile rhesus macaques, the role of the thymus in peripheral t cell homeostasis and to assess the significance of thymic output in siv infection. by monitoring the changes in phenotypic t cell markers as well as in the numbers of tcr excisional circles--a recently described marker for recent thymic emigrants--following thymectomy, we present evidence that surgical thymectomy in juvenile macaques results in a faster deca ... | 2005 | 15593297 |
| dermavir: a novel topical vaccine for hiv/aids. | human immunodeficiency virus (hiv) vaccines have the potential to improve antiretroviral drug treatment by inducing cytotoxic killing of hiv-infected cells. prophylactic vaccines utilize new antigens to initiate immunity; however, in hiv-infected individuals the load of viral antigen is not the limiting factor for the restoration of immune responses. here we describe a novel immunization strategy with dermavir that improves viral antigen presentation using dendritic cells (dc). dermavir contains ... | 2005 | 15654970 |
| trichomonad gastritis in rhesus macaques (macaca mulatta) infected with simian immunodeficiency virus. | in a retrospective study, 51 cases of gastritis (14%) were identified from among 341 necropsies performed on simian immunodeficiency virus (siv)-infected rhesus macaques (macaca mulatta) at the new england primate research center from 1993 to 2001. protozoa were seen in the stomach of 13 monkeys (25%) with gastritis. two histopathologic manifestations of gastritis were observed: seven cases of lymphoplasmacytic gastritis with trichomonad trophozoites within lumens of gastric glands and four case ... | 2005 | 15657268 |
| biodistribution and persistence of an mva-vectored candidate hiv vaccine in siv-infected rhesus macaques and scid mice. | recombinant modified vaccinia virus ankara (mva) is together with a few other attenuated viral vectors on the forefront of human immunodeficiency virus type 1 (hiv-1) vaccine development. as such, mva-vectored vaccines are likely to be administered into immunocompromized individuals. here, we demonstrated in a good laboratory practice study safety and biological clearance of candidate hiv-1 vaccine mva.hiva in simian immunodeficiency virus (siv)-infected rhesus macaques and mice with a severe co ... | 2005 | 15670887 |
| dynamic immune responses maintain cytotoxic t lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants. | viral escape from cytotoxic t lymphocytes (ctls) can undermine immune control of human immunodeficiency virus 1. it is therefore important to assess the stability of viral mutations in ctl epitopes after transmission to naive hosts. here we demonstrate the persistence of mutations in a dominant ctl epitope after transmission of simian immunodeficiency virus variants to major histocompatibility complex-matched rhesus monkeys. transient reversions to wild-type sequences occurred and elicited ctls ... | 2005 | 15685174 |
| evaluation of siv-lipopeptide immunizations administered by the intradermal route in their ability to induce antigen specific t-cell responses in rhesus macaques. | numerous clinical and experimental observations have shown that cellular immunity, in particular cd8+ t-lymphocytes, plays an important role in the control of hiv infection. we have focused on a lipopeptide vaccination strategy that has been shown to induce polyepitopic t-cell responses in both animals and humans, in order to deliver simian immunodeficiency virus (siv) antigens to rhesus macaques. given the relevance of antigen administration route in the development of an effective cellular imm ... | 2005 | 15708309 |
| early antiretroviral therapy for simian immunodeficiency virus infection leads to mucosal cd4+ t-cell restoration and enhanced gene expression regulating mucosal repair and regeneration. | simian immunodeficiency virus (siv) and human immunodeficiency virus (hiv) infections lead to rapid depletion of cd4(+) t cells from gut-associated lymphoid tissue (galt). although the administration of antiretroviral therapy (art) has been shown to increase cd4(+) t-cell levels in the peripheral blood in both siv and hiv infections, its efficacy in restoring intestinal mucosal cd4(+) t cells has not been well investigated. to gain insights into the molecular mechanisms of virally induced disrup ... | 2005 | 15708990 |
| species-specific variation in the b30.2(spry) domain of trim5alpha determines the potency of human immunodeficiency virus restriction. | retroviruses encounter dominant postentry restrictions in cells of particular species. human immunodeficiency virus type 1 (hiv-1) is blocked in the cells of old world monkeys by trim5alpha, a tripartite motif (trim) protein composed of ring, b-box 2, coiled-coil, and b30.2(spry) domains. rhesus monkey trim5alpha (trim5alpha(rh)) more potently blocks hiv-1 infection than human trim5alpha (trim5alpha(hu)). here, by studying chimeric trim5alpha proteins, we demonstrate that the major determinant o ... | 2005 | 15709033 |
| simian immunodeficiency virus (siv) envelope quasispecies transmission and evolution in infant rhesus macaques after oral challenge with uncloned sivmac251: increased diversity is associated with neutralizing antibodies and improved survival in previously immunized animals. | oral infection of infant macaques with simian immunodeficiency virus (siv) is a useful animal model to test interventions to reduce postnatal hiv transmission via breast-feeding. we previously demonstrated that immunization of infant rhesus macaques with either modified vaccinia virus ankara (mva) expressing siv gag, pol and env, or live-attenuated sivmac1a11 resulted in lower viremia and longer survival compared to unimmunized controls after oral challenge with virulent sivmac251 (van rompay et ... | 2005 | 15710048 |
| protection of rhesus monkeys against infection with minimally pathogenic simian-human immunodeficiency virus: correlations with neutralizing antibodies and cytotoxic t cells. | we studied the capacity of active immunization of rhesus monkeys with hiv-1 envelope protein (env) to induce primary virus cross-reactive neutralizing antibodies to prevent infection following intravenous challenge with simian-human immunodeficiency virus (shiv). monkeys were immunized with the human immunodeficiency type 1 (hiv-1) strain r2 env. initially, the env was expressed in vivo by an alphavirus replicon particle system, and then it was administered as soluble oligomeric gp140. concurren ... | 2005 | 15731230 |
| comparisons of brain metabolites observed by hrmas 1h nmr of intact tissue and solution 1h nmr of tissue extracts in siv-infected macaques. | the objective of this study was to compare ex vivo proton high-resolution magic angle spinning magnetic resonance spectra of intact tissue with those spectra obtained by solution (1)h nmr of brain extracts of the same sample. sixteen brain tissue samples from simian immunodeficiency virus-infected rhesus macaques from both frontal cortex and putamen were evaluated by comparing brain metabolite quantities of n-acetylaspartate (naa), choline-containing compounds (cho), myo-inositol (mi), creatine ... | 2005 | 15759297 |
| divergent host responses during primary simian immunodeficiency virus sivsm infection of natural sooty mangabey and nonnatural rhesus macaque hosts. | to understand how natural sooty mangabey hosts avoid aids despite high levels of simian immunodeficiency virus (siv) sivsm replication, we inoculated mangabeys and nonnatural rhesus macaque hosts with an identical inoculum of uncloned sivsm. the unpassaged virus established infection with high-level viral replication in both macaques and mangabeys. a species-specific, divergent immune response to siv was evident from the first days of infection and maintained in the chronic phase, with macaques ... | 2005 | 15767406 |
| peak siv replication in resting memory cd4+ t cells depletes gut lamina propria cd4+ t cells. | in early simian immunodeficiency virus (siv) and human immunodeficiency virus-1 (hiv-1) infections, gut-associated lymphatic tissue (galt), the largest component of the lymphoid organ system, is a principal site of both virus production and depletion of primarily lamina propria memory cd4+ t cells; that is, cd4-expressing t cells that previously encountered antigens and microbes and homed to the lamina propria of galt. here, we show that peak virus production in gut tissues of siv-infected rhesu ... | 2005 | 15793562 |
| expression of cd154 by a simian immunodeficiency virus vector induces only transitory changes in rhesus macaques. | human immunodeficiency virus infection is characterized by dysregulation of antigen-presenting cell function and defects in cell-mediated immunity. recent evidence suggests that impaired ability of cd4+ t cells to upregulate the costimulatory molecule cd154 is at the core of this dysregulation. to test the hypothesis that increased expression of cd154 on infected cd4+ t cells could modulate immune function, we constructed a replication-competent simian immunodeficiency virus (siv) vector that ex ... | 2005 | 15795254 |
| retroviral recombination in vivo: viral replication patterns and genetic structure of simian immunodeficiency virus (siv) populations in rhesus macaques after simultaneous or sequential intravaginal inoculation with sivmac239deltavpx/deltavpr and sivmac239deltanef. | to characterize the occurrence, frequency, and kinetics of retroviral recombination in vivo, we intravaginally inoculated rhesus macaques, either simultaneously or sequentially, with attenuated simian immunodeficiency virus (siv) strains having complementary deletions in their accessory genes and various degrees of replication impairment. in monkeys inoculated simultaneously with sivmac239deltavpx/deltavpr and sivmac239deltanef, recombinant wild-type (wt) virus and wild-type levels of plasma vir ... | 2005 | 15795274 |
| cd4-independent entry and replication of simian immunodeficiency virus in primary rhesus macaque astrocytes are regulated by the transmembrane protein. | previous studies have demonstrated that the genetic determinants of simian immunodeficiency virus (siv) neurovirulence map to the env and nef genes. recent studies from our laboratory demonstrated that siv replication in primary rhesus macaque astrocyte cultures is dependent upon the nef gene. here, we demonstrate that macrophage tropism is not sufficient for replication in astrocytes and that specific amino acids in the transmembrane (tm) portion of env are also important for optimal siv replic ... | 2005 | 15795280 |
| quantitative neuropathologic correlates of changes in ratio of n-acetylaspartate to creatine in macaque brain. | to elucidate the neuropathologic basis of transient changes in the ratio of n-acetylaspartate (naa) to creatine (cr) in the primate brain by using a simian immunodeficiency virus (siv)-infected macaque model of the neurologic manifestation of acquired immune deficiency syndrome. | 2005 | 15798152 |
| enhanced immunity and protective efficacy against sivmac251 intrarectal challenge following ad-siv priming by multiple mucosal routes and gp120 boosting in mpl-se. | previously, 39% of rhesus macaques primed orally, intranasally, and intratracheally with adenovirus (ad)-simian immunodeficiency virus (siv) recombinants and boosted with gp120 in monophosphoryl lipid a-stable emulsion (mpl-se) remained aviremic or cleared or controlled viremia at the threshold of detection following siv(mac251) intrarectal challenge (study b). in contrast, no macaques primed orally and intranasally with ad-siv recombinants and boosted with gp120 in quillaja saponaria-21 exhibit ... | 2005 | 15802969 |
| dysfunction of simian immunodeficiency virus/simian human immunodeficiency virus-induced il-2 expression by central memory cd4+ t lymphocytes. | production of il-2 and ifn-gamma by cd4+ t lymphocytes is important for the maintenance of a functional immune system in infected individuals. in the present study, we assessed the cytokine production profiles of functionally distinct subsets of cd4+ t lymphocytes in rhesus monkeys infected with pathogenic or attenuated siv/simian human immunodeficiency virus (shiv) isolates, and these responses were compared with those in vaccinated monkeys that were protected from immunodeficiency following pa ... | 2005 | 15814700 |
| relationships between astrogliosis and 1h mr spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model. | in vivo 1h mr spectroscopy demonstrates elevated choline (cho)/creatine (cr) and myo-inositol (mi)/cr in many neurologic diseases that has been ascribed to gliosis. we tested the hypotheses that in vivo cho/cr and/or mi/cr levels are correlated with glial fibrillary acidic protein (gfap) immunostains and that the changes are water-soluble metabolites. | 2005 | 15814917 |
| novel simian immunodeficiency virus ctl epitopes restricted by mhc class i molecule mamu-b*01 are highly conserved for long term in dna/mva-vaccinated, shiv-challenged rhesus macaques. | simian immunodeficiency virus (siv) infection of rhesus macaques provides an excellent model for investigating the basis of protective immunity against human immunodeficiency virus (hiv). one limitation of this model, however, has been the availability of a small number of known mhc class i-restricted ctl epitopes for investigating virus-specific immune responses. we assessed ctl responses against siv gag in a cohort of dna/modified vaccinia virus ankara (mva)-vaccinated/simian-human immunodefic ... | 2005 | 15824066 |
| comparison of susceptibility to sivmac239 infection between cd4(+) and cd4(+)8(+) t cells. | cd4-bearing t cells are the primary targets for human immunodeficiency virus type 1(hiv-1)/simian immunodeficiency virus (siv) infection. however, it is unclear whether the susceptibility of cd4-bearing t cells including cd4 single positive and cd4/8 double positive t cells to hiv/siv infection is the same or not. in this study, we compared the susceptibility to siv infection between cd4(+) and cd4(+)8(+) t cells, using herpesvirus saimiri (hvs)-transformed cd4(+) and cd4(+)8(+) t cells establis ... | 2005 | 15841338 |
| intestinal stromal tumors in a simian immunodeficiency virus-infected, simian retrovirus-2 negative rhesus macaque (macaca mulatta). | multifocal submucosal stromal tumors were diagnosed in a 5.5-year-old rhesus macaque (macaca mulatta) experimentally infected with simian immunodeficiency virus, strain sivsme660, and cd4+ t cell depleted. the animal was negative for simian retroviruses, srv-1, -2, and -5. polymerase chain reaction analysis of dna from tumor and spleen tissue revealed abundant, preferential presence of retroperitoneal fibromatosis herpesvirus, the macaque homologue of the kaposi sarcoma-associated herpesvirus (h ... | 2005 | 15872392 |
| delineation of multiple subpopulations of natural killer cells in rhesus macaques. | natural killer (nk) cells in rhesus macaques have been variably defined as cd3- cd16+ or cd3- cd8+, although only limited efforts have been made to validate these definitions rigorously. to better understand the role of nk cells in macaque disease models, we undertook a multiparameter analysis of macaque nk cells employing four-colour flow cytometry and a panel of lineage-specific and non-lineage-specific lymphocyte markers. using this approach, we identified two distinct populations of candidat ... | 2005 | 15885126 |
| the contribution of ring and b-box 2 domains to retroviral restriction mediated by monkey trim5alpha. | trim5alpha is a cytoplasmic protein that mediates a post-entry block to infection by some retroviruses. trim5alpha contains a tripartite motif (trim), which includes ring, b-box 2, and coiled-coil domains, and a c-terminal b30.2 (spry) domain. we investigated the contribution of the ring and b-box 2 domains to the antiretroviral activity of rhesus monkey trim5alpha (trim5alpharh), which potently restricts infection by human immunodeficiency virus, type 1 (hiv-1) and simian immunodeficiency virus ... | 2005 | 15897199 |
| cd8+ t cell dynamics during primary simian immunodeficiency virus infection in macaques: relationship of effector cell differentiation with the extent of viral replication. | immunological and virological events that occur during the earliest stages of hiv-1 infection are now considered to have a major impact on subsequent disease progression. we observed changes in the frequencies of cd8(bright) t cells expressing different chemokine receptors in the peripheral blood and lymph nodes of rhesus macaques during the acute phase of the pathogenic sivmac251 infection; the frequency of cd8(bright) t cells expressing cxcr4 decreased, while the frequency of those expressing ... | 2005 | 15905532 |
| resting naive cd4+ t cells are massively infected and eliminated by x4-tropic simian-human immunodeficiency viruses in macaques. | unlike hiv-1 and simian immunodeficiency virus (siv), which induce a slow, unrelenting loss of immune function spanning several years, highly pathogenic simian-human immunodeficiency viruses (shivs) induce a rapid, complete, and irreversible depletion of cd4(+) t lymphocytes in rhesus monkeys within weeks of infection, leading to death from immunodeficiency. we recently reported that, because these shivs exclusively use the cxcr4 coreceptor for cell entry, they target naive cd4(+) t cells for de ... | 2005 | 15911767 |
| suppression of virus load by highly active antiretroviral therapy in rhesus macaques infected with a recombinant simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. | we have modeled highly active antiretroviral therapy (haart) for aids in rhesus macaques infected with a chimera (rt-shiv) of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type-1 (hiv-1). seven rt-shiv-infected macaques were treated with a combination of efavirenz (200 mg orally once daily), lamivudine (8 mg/kg subcutaneously once daily), and tenofovir (30 mg/kg subcutaneously once daily). plasma viral rna levels in all animals were reduced by m ... | 2005 | 15919889 |
| immunization of macaques with single-cycle simian immunodeficiency virus (siv) stimulates diverse virus-specific immune responses and reduces viral loads after challenge with sivmac239. | genetically engineered simian immunodeficiency viruses (siv) that is limited to a single cycle of infection was evaluated as a nonreplicating aids vaccine approach for rhesus macaques. four mamu-a*01(+) macaques were inoculated intravenously with three concentrated doses of single-cycle siv (scsiv). each dose consisted of a mixture of approximately equivalent amounts of scsiv strains expressing the siv(mac)239 and siv(mac)316 envelope glycoproteins with mutations in nef that prevent major histoc ... | 2005 | 15919923 |
| improving the sensitivity of the elispot analyses of antigen-specific cellular immune responses in rhesus macaques. | the close similarities in hematopoietic and immune systems of humans and rhesus macaques (macaca mulatta) make them the desired nonhuman primate animal model for developing vaccines against infectious diseases relevant to humans. the best example is the simian immunodeficiency virus infection in macaques as a model for aids, resulting from infection of humans by hiv-1. vaccine efficacy against viruses depends on priming cell-mediated immunity by the use of sensitive assays that can accurately de ... | 2005 | 15937350 |
| effect of cd8+ lymphocyte depletion on virus containment after simian immunodeficiency virus sivmac251 challenge of live attenuated sivmac239delta3-vaccinated rhesus macaques. | although live attenuated vaccines can provide potent protection against simian immunodeficiency virus (siv) and simian-human immunodeficiency virus challenges, the specific immune responses that confer this protection have not been determined. to test whether cellular immune responses mediated by cd8+ lymphocytes contribute to this vaccine-induced protection, we depleted rhesus macaques vaccinated with the live attenuated virus sivmac239delta3 of cd8+ lymphocytes and then challenged them with si ... | 2005 | 15956558 |
| dna vaccines expressing different forms of simian immunodeficiency virus antigens decrease viremia upon sivmac251 challenge. | we have tested the efficacy of dna immunization as a single vaccination modality for rhesus macaques followed by highly pathogenic sivmac251 challenge. to further improve immunogenicity of the native proteins, we generated expression vectors producing fusion of the proteins gag and env to the secreted chemokine mcp3, targeting the viral proteins to the secretory pathway and to a beta-catenin (cate) peptide, targeting the viral proteins to the intracellular degradation pathway. macaques immunized ... | 2005 | 15956591 |
| the effect of micronutrient supplementation on disease progression and death in simian immunodeficiency virus-infected juvenile male rhesus macaques. | we investigated the impact that micronutrient supplementation has on the progression of simian acquired immunodeficiency syndrome (saids). | 2005 | 15962226 |
| pharmacology and pharmacokinetics of the antiviral agent beta-d-2',3'-dideoxy-3'-oxa-5-fluorocytidine in cells and rhesus monkeys. | beta-d-2',3'-dideoxy-3'-oxa-5-fluorocytidine (d-fdoc) is an effective inhibitor of human immunodeficiency virus 1 (hiv-1) and hiv-2, simian immunodeficiency virus, and hepatitis b virus (hbv) in vitro. the purpose of this study was to evaluate the intracellular metabolism of d-fdoc in human hepatoma (hepg2), human t-cell lymphoma (cem), and primary human peripheral blood mononuclear (pbm) cells by using tritiated compound. by 24 h, the levels of d-fdoc-triphosphate (d-fdoc-tp) were 2.8 +/- 0.4, ... | 2005 | 15980324 |
| a specific region of 37 amino acid residues in the spry (b30.2) domain of african green monkey trim5alpha determines species-specific restriction of simian immunodeficiency virus sivmac infection. | human immunodeficiency virus type 1 (hiv-1) efficiently enters cells of old world monkeys but encounters a block before reverse transcription. this restriction is mediated by a dominant repressive factor. recently, a member of the tripartite motif (trim) family proteins, trim5alpha, was identified as a blocking factor in a rhesus macaque cdna library. among old world monkey cell lines, the african green monkey kidney cell line cv1 is highly resistant to not only hiv-1 but also simian immunodefic ... | 2005 | 15994780 |
| propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. | in the current global aids pandemic, more than half of new human immunodeficiency virus type 1 (hiv-1) infections are acquired by women through intravaginal hiv exposure. for this study, we explored pathogenesis issues relevant to the development of effective vaccines to prevent infection by this route, using an animal model in which female rhesus macaques were exposed intravaginally to a high dose of simian immunodeficiency virus (siv). we examined in detail the events that transpire from hours ... | 2005 | 15994816 |
| cd8+ t-lymphocyte response to major immunodominant epitopes after vaginal exposure to simian immunodeficiency virus: too late and too little. | in the acute stage of infection following sexual transmission of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv), virus-specific cd8+ t-lymphocyte responses partially control but do not eradicate infection from the lymphatic tissues (lts) or prevent the particularly massive depletion of cd4+ t lymphocytes in gut-associated lymphatic tissue (galt). we explored hypothetical explanations for this failure to clear infection and prevent cd4+ t-lymphocyte loss in the siv/rhe ... | 2005 | 15994817 |
| increased viral replication in simian immunodeficiency virus/simian-hiv-infected macaques with self-administering model of chronic alcohol consumption. | alcohol abuse constitutes a major cohort among hiv-infected individuals. the precise effect of alcohol addiction on hiv pathogenesis remains inconclusive, however. this study was designed to determine the effect of alcohol dependence on virus replication and cd4 profiles in simian immunodeficiency virus/simian-hiv-infected rhesus macaques. a group of 3 male indian rhesus macaques was adapted to a self-drinking model of alcohol consumption, whereas another group of 3 macaques was provided a nutra ... | 2005 | 16010157 |
| regulation of apobec3f and human immunodeficiency virus type 1 vif by vif-cul5-elonb/c e3 ubiquitin ligase. | the human cytidine deaminase apobec3f (h-a3f), a protein related to the previously recognized antiviral factor apobec3g (h-a3g), has antiviral activity against human immunodeficiency virus type 1 (hiv-1) that is suppressed by the viral protein vif. the mechanism of hiv-1 vif-mediated suppression of h-a3f is not fully understood. here, we demonstrate that while h-a3f, like h-a3g, was able to suppress primate lentiviruses other than hiv-1 (simian immunodeficiency virus from african green monkeys [ ... | 2005 | 16014920 |
| mucosal alloimmunization elicits t-cell proliferation, cc chemokines, ccr5 antibodies and inhibition of simian immunodeficiency virus infectivity. | the hypothesis was tested that mucosal stimulation with unmatched mononuclear cells would induce systemic alloimmune responses. rectal or vaginal mucosal administration of 10(4)-10(7) unmatched mononuclear cells induced significant dose-dependent t-cell proliferation stimulated by the allogeneic cells in rhesus macaques. this was associated with a significant upregulation of cd8(+) t-cell-derived suppressor factor, as well as the cc chemokines ccl3, ccl4 and ccl5. in addition, there was a dose-d ... | 2005 | 16033970 |
| priming with plasmid dnas expressing interleukin-12 and simian immunodeficiency virus gag enhances the immunogenicity and efficacy of an experimental aids vaccine based on recombinant vesicular stomatitis virus. | of the various approaches being developed as prophylactic hiv vaccines, those based on a heterologous plasmid dna prime, live vector boost vaccination regimen appear especially promising in the nonhuman primate/simian-human immunodeficiency virus (shiv) challenge model. in this study, we sought to determine whether a series of intramuscular priming immunizations with a plasmid dna vaccine expressing sivgag p39, in combination with plasmid expressed rhesus il-12, could effectively enhance the imm ... | 2005 | 16060834 |
| a single amino acid change and truncated tm are sufficient for simian immunodeficiency virus to enter cells using ccr5 in a cd4-independent pathway. | entry of hiv and siv into susceptible cells is mediated by cd4 and chemokine receptors, which act as coreceptors. to study cell entry of siv, we constructed a cell line, xklusiv, derived from non-susceptible human k562 cells, that express the firefly luciferase reporter gene under control of a minimal siv long terminal repeat (ltr). using these susceptible cells, we studied the entry of a well-characterized molecularly cloned macrophage-tropic siv. xklusiv cells that express rhesus macaque cd4 a ... | 2005 | 16061266 |
| simian immunodeficiency virus disrupts extended lengths of the blood--brain barrier. | it is known that there is disruption of the blood-brain barrier during terminal aids encephalitis in both human immunodeficiency virus (hiv)-infected humans and simian immunodeficiency virus (siv)-infected rhesus macaques. much, although by no means all, of the neuropathological findings of hiv and siv infection involves accumulation of monocytes/macrophages that have likely crossed the blood-brain barrier (bbb). there is no convincing, rigorous, demonstration of hiv (or siv) infecting endotheli ... | 2005 | 16128918 |
| immune mechanisms associated with protection from vaginal siv challenge in rhesus monkeys infected with virulence-attenuated shiv 89.6. | although live-attenuated human immunodeficiency virus-1 (hiv) vaccines may never be used clinically, these vaccines have provided the most durable protection from intravenous (iv) challenge in the simian immunodeficiency virus (siv)/rhesus macaque model. systemic infection with virulence attenuated-simian-human immunodeficiency virus (shiv) 89.6 provides protection against vaginal siv challenge. this paper reviews the findings related to the innate and adaptive immune responses and the role of i ... | 2005 | 16128922 |
| increase of c1q biosynthesis in brain microglia and macrophages during lentivirus infection in the rhesus macaque is sensitive to antiretroviral treatment with 6-chloro-2',3'-dideoxyguanosine. | complement activation in the brain contributes to the pathology of neuroinflammatory and neurodegenerative diseases such as neuro-aids. using semiquantitative in situ hybridization and immunohistochemistry, we observed an early and sustained increase in the expression of c1q, the initial recognition subcomponent of the classical complement cascade, in the cns during simian immunodeficiency virus (siv) infection of rhesus macaques. cells of the microglial/macrophage lineage were the sources for c ... | 2005 | 16137563 |
| differential restriction of human immunodeficiency virus type 2 and simian immunodeficiency virus sivmac by trim5alpha alleles. | primate lentiviruses have narrow host ranges, due in part to their sensitivities to mammalian intracellular antiviral factors such as apobec3g and trim5alpha. despite the protection provided by this innate immune system, retroviruses are able to transfer between species where they can cause disease. this is true for sooty mangabey simian immunodeficiency virus, which has transferred to humans as hiv-2 and to rhesus macaques as sivmac, where it causes aids. here we examine the sensitivities of th ... | 2005 | 16140735 |
| use of molecular beacons for rapid, real-time, quantitative monitoring of cytotoxic t-lymphocyte epitope mutations in simian immunodeficiency virus. | immune pressure on lentiviruses exerted by cytotoxic t lymphocytes (ctl) selects for virus ctl epitope mutations. currently employed methods for monitoring emerging ctl epitope mutations rely on the labor-intensive and time-consuming techniques of virus population or clonal sequencing. here we describe the development of a high-throughput quantitative reverse transcription-pcr assay that facilitates large-scale ctl epitope monitoring. this approach utilizes both sequence-specific molecular beaco ... | 2005 | 16145140 |
| temporal and anatomic relationship between virus replication and cytokine gene expression after vaginal simian immunodeficiency virus infection. | the current knowledge about early innate immune responses at mucosal sites of human immunodeficiency virus (hiv) entry is limited but likely to be important in the design of effective hiv vaccines against heterosexual transmission. this study examined the temporal and anatomic relationship between virus replication, lymphocyte depletion, and cytokine gene expression levels in mucosal and lymphoid tissues in a vaginal-transmission model of hiv in rhesus macaques. the results of the study show tha ... | 2005 | 16160143 |