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multiple vaccine-elicited nonneutralizing antienvelope antibody activities contribute to protective efficacy by reducing both acute and chronic viremia following simian/human immunodeficiency virus shiv89.6p challenge in rhesus macaques.we have shown that following priming with replicating adenovirus type 5 host range mutant (ad5hr)-human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) recombinants, boosting with gp140 envelope protein enhances acute-phase protection against intravenous simian/human immunodeficiency virus (shiv)(89.6p) challenge compared to results with priming and no boosting or boosting with an hiv polypeptide representing the cd4 binding site of gp120. we retrospectively analyzed antibodies ...201020444898
in vivo cd8+ t-cell suppression of siv viremia is not mediated by ctl clearance of productively infected cells.the cd8+ t-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. we studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (siv) infected rhesus macaques following cd8+ t-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with siv. as previously described, plasma viral load (vl) increased followin ...201020126442
dynamics of haplotype frequency change in a cd8+tl epitope of simian immunodeficiency virus.deep pyrosequencing of a cd8+tl epitope from the tat protein of simian immunodeficiency virus (siv) from four infected rhesus macaques carrying the restricting mhc allele (mamu-a*01) for that epitope, revealed that natural selection favoring escape mutations led to an increase in the frequency of haplotypes in the epitope region that differed from the inoculum. after 20 weeks of infection, a new sequence haplotype in the epitope region had increased to a frequency greater than 50% in each of the ...201020149896
induction of antibody-mediated neutralization in sivmac239 by a naturally acquired v3 mutation.achieving humoral immunity against human immunodeficiency virus (hiv) is a major obstacle in aids vaccine development. despite eliciting robust humoral responses to hiv, exposed hosts rarely produce broadly neutralizing antibodies. the present study utilizes simian immunodeficiency virus (siv) to identify viral epitopes that conferred antibody neutralization to clone siv/17e-cl, an in vivo variant derived from neutralization resistant sivmac239. neutralization assays using rhesus macaque monoclo ...201020153009
interleukin 18 and cardiovascular disease in hiv-1 infection: a partner in crime?cardiovascular disease has been frequent in hiv-infected patients both before and after the advent of antiretroviral therapy (haart). the pathogenic basis for the increase of cardiovascular disease, in particular myocardial lesions, may involve hiv-1 itself or other mechanisms including endothelial dysfunction, activation of proinflammatory cytokines, and changes in platelets, which lead to atherosclerotic lesions of blood vessels. in the last decade, among the proinflammatory cytokines, interle ...201020216908
peripheral blood cd4 and cd8 double-positive t cells of rhesus macaques become vulnerable to simian immunodeficiency virus by in vitro stimulation due to the induction of ccr5.in vivo simian immunodeficiency virus (siv) challenge of macaques demonstrated the earlier disappearance of cd4 and cd8 double-positive (dp) t cells than cd4 single-positive t cells, although its mechanism remains unclear. here we found that peripheral dp t cells were readily induced to express ccr5, a secondary receptor for siv, by in vitro stimulation with either concanavalin a or anti-cd3/cd28 monoclonal antibodies. activated dp t cells were more vulnerable to siv infection, indicating that t ...201020224239
identification of 81lgxgxxixw89 and 171edrw174 domains from human immunodeficiency virus type 1 vif that regulate apobec3g and apobec3f neutralizing activity.the human cytidine deaminases apobec3g (a3g) and apobec3f (a3f) potently restrict human immunodeficiency virus type 1 (hiv-1) replication, but they are neutralized by the viral protein vif. vif bridges a3g and a3f with a cullin 5 (cul5)-based e3 ubiquitin ligase and mediates their proteasomal degradation. this mechanism has been extensively studied, and several vif domains have been identified that are critical for a3g and a3f neutralization. here, we identified two additional domains. via seque ...201020335268
systemic spironucleosis in 2 immunodeficient rhesus macaques (macaca mulatta).spironucleus spp are parasites of fish and terrestrial vertebrates, including mice and turkeys, that rarely cause extraintestinal disease. two rhesus macaques (macaca mulatta) were experimentally inoculated with simian immunodeficiency virus mac251. both progressed to simian acquired immune deficiency syndrome within 1 year of inoculation and developed systemic protozoal infections in addition to common opportunistic infections, including rhesus cytomegalovirus, rhesus lymphocryptovirus, and rhe ...201020351359
autologous neutralizing antibodies to the transmitted/founder viruses emerge late after simian immunodeficiency virus sivmac251 infection of rhesus monkeys.while the simian immunodeficiency virus (siv)-infected rhesus monkey is an important animal model for human immunodeficiency virus type 1 (hiv-1) infection of humans, much remains to be learned about the evolution of the humoral immune response in this model. in hiv-1 infection, autologous neutralizing antibodies emerge 2 to 3 months after infection. however, the ontogeny of the siv-specific neutralizing antibody response in mucosally infected animals has not been defined. we characterized the k ...201020357097
depo-provera does not alter disease progression in sivmac-infected female chinese rhesus macaques.depo-provera (medroxyprogesterone acetate), a long-acting derivative of progesterone, is utilized during many nonhuman primate microbicide studies to facilitate simian immunodeficiency virus (siv) infection by thinning the vaginal epithelium. to date, the systemic effects of this steroid hormone in regard to siv/hiv pathogenesis are not well understood, but an increase in infection rates and lymphoproliferation following progesterone application has been reported. therefore, a proactive study us ...201020377424
expression, purification, crystallization and preliminary x-ray diffraction analysis of rhesus macaque cd8alphaalpha homodimer.as a t-cell co-receptor, cd8 binds to mhc class i molecules and plays a pivotal role in the activation of cytotoxic t lymphocytes. to date, structures of cd8 have been solved for two different mammals: human and mouse. the infection of rhesus macaques (macaca mulatta) by simian immunodeficiency virus (siv) is the best animal model for studying hiv. in this study, the rhesus macaque cd8 (rcd8) alphaalpha homodimer was obtained and rcd8alpha exodomain protein crystals were successfully obtained fo ...201020383016
contributions of mamu-a*01 status and trim5 allele expression, but not ccl3l copy number variation, to the control of sivmac251 replication in indian-origin rhesus monkeys.ccl3 is a ligand for the hiv-1 co-receptor ccr5. there have recently been conflicting reports in the literature concerning whether ccl3-like gene (ccl3l) copy number variation (cnv) is associated with resistance to hiv-1 acquisition and with both viral load and disease progression following infection with hiv-1. an association has also been reported between ccl3l cnv and clinical sequelae of the simian immunodeficiency virus (siv) infection in vivo in rhesus monkeys. the present study was initia ...201020585621
maintenance or emergence of chronic phase secondary cytotoxic t lymphocyte responses after loss of acute phase immunodominant responses does not protect siv-infected rhesus macaques from disease progression.the simian immunodeficiency virus- (siv-) infected rhesus macaque is the preferred animal model for vaccine development, but the correlates of protection in this model are not completely understood. in this paper, we document the cytotoxic t lymphocyte (ctl) response to siv and its effects on viral evolution in an effort to identify events associated with disease progression regardless of mhc allele expression. we observed the evolution of epitopes targeted by ctls in a group of macaques that in ...201020589067
limited cd4+ t cell proliferation leads to preservation of cd4+ t cell counts in siv-infected sooty mangabeys.human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) infections result in chronic virus replication and progressive depletion of cd4+ t cells, leading to immunodeficiency and death. in contrast, 'natural hosts' of siv experience persistent infection with high virus replication but no severe cd4+ t cell depletion, and remain aids-free. one important difference between pathogenic and non-pathogenic infections is the level of activation and proliferation of cd4+ t cells. we an ...201020591864
identification of a critical t(q/d/e)x5adx2(i/l) motif from primate lentivirus vif proteins that regulate apobec3g and apobec3f neutralizing activity.primate lentiviruses are unique in that they produce several accessory proteins to help in the establishment of productive viral infection. the major function of these proteins is to clear host resistance factors that inhibit viral replication. vif is one of these proteins. it functions as an adaptor that binds to the cytidine deaminases apobec3g (a3g) and apobec3f (a3f) and bridges them to a cullin 5 (cul5) and elongin (elo) b/c e3 ubiquitin ligase complex for proteasomal degradation. so far, 1 ...201020592083
a limited number of simian immunodeficiency virus (siv) env variants are transmitted to rhesus macaques vaginally inoculated with sivmac251.single-genome amplification (sga) and sequencing of hiv-1 rna in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. use of this strategy as a means for identifying transmitted viruses suggested that intrarectal simian immunodeficiency virus (siv) inoculation of macaques recapitulates key features of human rectal infection. however, no studies have used the sga strategy to identify vaginally tra ...201020463069
proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated neuroaids.despite the advent of highly active anti-retroviral therapy (haart), hiv-associated neurocognitive disorders continue to be a significant problem. in efforts to understand and alleviate neurocognitive deficits associated with hiv, we used an accelerated simian immunodeficiency virus (siv) macaque model of neuroaids to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury.201020479889
the most common chinese rhesus macaque mhc class i molecule shares peptide binding repertoire with the hla-b7 supertype.of the two rhesus macaque subspecies used for aids studies, the simian immunodeficiency virus-infected indian rhesus macaque (macaca mulatta) is the most established model of hiv infection, providing both insight into pathogenesis and a system for testing novel vaccines. despite the chinese rhesus macaque potentially being a more relevant model for aids outcomes than the indian rhesus macaque, the chinese-origin rhesus macaques have not been well-characterized for their major histocompatibility ...201020480161
lineage-specific t-cell reconstitution following in vivo cd4+ and cd8+ lymphocyte depletion in nonhuman primates.many features of t-cell homeostasis in primates are still unclear, thus limiting our understanding of aids pathogenesis, in which t-cell homeostasis is lost. here, we performed experiments of in vivo cd4(+) or cd8(+) lymphocyte depletion in 2 nonhuman primate species, rhesus macaques (rms) and sooty mangabeys (sms). whereas rms develop aids after infection with simian immunodeficiency virus (siv), siv-infected sms are typically aids-resistant. we found that, in both species, most cd4(+) or cd8(+ ...201020484087
downregulation of robust acute type i interferon responses distinguishes nonpathogenic simian immunodeficiency virus (siv) infection of natural hosts from pathogenic siv infection of rhesus macaques.the mechanisms underlying the aids resistance of natural hosts for simian immunodeficiency virus (siv) remain unknown. recently, it was proposed that natural siv hosts avoid disease because their plasmacytoid dendritic cells (pdcs) are intrinsically unable to produce alpha interferon (ifn-alpha) in response to siv rna stimulation. however, here we show that (i) acute siv infections of natural hosts are associated with a rapid and robust type i ifn response in vivo, (ii) pdcs are the principal in ...201020484518
methamphetamine increases brain viral load and activates natural killer cells in simian immunodeficiency virus-infected monkeys.methamphetamine (meth) abuse increases risky behaviors that contribute to the spread of hiv infection. in addition, because hiv and meth independently affect physiological systems including the central nervous system, hiv-induced disease may be more severe in drug users. we investigated changes in blood and brain viral load as well as differences in immune cells in chronically simian immunodeficiency virus-infected rhesus macaques that were either administered meth or used as controls. although ...201020489154
simian immunodeficiency virus-specific cd4+ t cells from successful vaccinees target the siv gag capsid.we recently demonstrated that vaccinated rhesus macaques controlled viral replication of a heterologous siv challenge. here, we analyzed anamnestic siv-specific cd4+ t-cell responses expanding immediately after challenge and show that successful vaccinees consistently targeted a short region of the gag-p27 capsid (amino acids 249-291). we have also defined the major histocompatibility complex class ii (mhc-ii) restricting alleles for several of these responses and show that dq-restricted cd4+ t- ...201020812010
neutralizing antibodies in siv control: co-impact with t cells.human immunodeficiency virus type 1 (hiv-1) and pathogenic simian immunodeficiency virus (siv)-infected naïve hosts experience a characteristic absence of early and potent virus-specific neutralizing antibody (nab) responses preceding establishment of persistent infection. yet conversely, we have recently shown that nabs passively immunized in rhesus macaques at early post-siv challenge are capable of playing a critical role in non-sterile viremia control with implications of antibody-enhanced a ...201020510737
limited contribution of mucosal iga to simian immunodeficiency virus (siv)-specific neutralizing antibody response and virus envelope evolution in breast milk of siv-infected, lactating rhesus monkeys.breast milk transmission of human immunodeficiency virus (hiv) remains an important mode of infant hiv acquisition. interestingly, the majority of infants remain uninfected during prolonged virus exposure via breastfeeding, raising the possibility that immune components in milk prevent mucosal virus transmission. hiv-specific antibody responses are detectable in the milk of hiv-infected women and simian immunodeficiency virus (siv)-infected monkeys; however, the role of these humoral responses i ...201020519381
th17 cells and hiv infection.this review summarizes the recent literature about the potential perturbation and role of th17 cells in hiv pathogenesis. we discuss the recent findings on th17 deficiency in hiv/simian immunodeficiency virus (siv) infection and how this deficiency may impact the mucosal host defenses, potentially contributing to chronic immune activation.201020543592
th17 cells, hiv and the gut mucosal barrier.we will present recent studies on a subset of cd4 t helper cells, th17 cells, that appears to be critical for regulating gut mucosal immune responses against extracellular microbial pathogens and may serve as a link between innate and adaptive immune responses. implications of the loss of th17 cd4 t cells in hiv infection will be discussed in relation to the chronic immune activation and hiv pathogenesis.201020543596
th17 cells, job's syndrome and hiv: opportunities for bacterial and fungal infections.patients with hyper ige syndrome (hies) share with hiv patients a predisposition to infections, including candidiasis in autosomal dominant hies (ad-hies) and molluscum contagiosum and other viral infections in other disorders of elevated ige with infectious predilections. this review highlights the underlying pathogenesis of these diseases and their relevance to hiv infection.201020543597
viral decay kinetics in the highly active antiretroviral therapy-treated rhesus macaque model of aids.to prevent progression to aids, persons infected with human immunodeficiency virus type 1 (hiv-1) must remain on highly active antiretroviral therapy (haart) indefinitely since this modality does not eradicate the virus. the mechanisms involved in viral persistence during haart are poorly understood, but an animal model of haart could help elucidate these mechanisms and enable studies of hiv-1 eradication strategies. due to the specificity of non-nucleoside reverse transcriptase (rt) inhibitors ...201020668516
characterization of siv in the oral cavity and in vitro inhibition of siv by rhesus macaque saliva.human immunodeficiency virus (hiv) infections are rarely acquired via an oral route in adults. previous studies have shown that human whole saliva inhibits hiv infection in vitro, and multiple factors present in human saliva have been shown to contribute to this antiviral activity. despite the widespread use of simian immunodeficiency virus (siv)-infected rhesus macaques as models for hiv pathogenesis and transmission, few studies have monitored siv in the oral cavity of infected rhesus macaques ...201020672998
plasma proteomic analysis of simian immunodeficiency virus infection of rhesus macaques.lentiviral replication in its target cells affects a delicate balance between cellular cofactors required for virus propagation and immunoregulation for host defense. to better elucidate cellular proteins linked to viral infection, we tested plasma from rhesus macaques infected with the simian immunodeficiency viral strain sivsmm9, prior to, 10 days (acute), and 49 weeks (chronic) after viral infection. changes in plasma protein content were measured by quantitative mass spectrometry by isobaric ...201020677826
low-dose mucosal simian immunodeficiency virus infection restricts early replication kinetics and transmitted virus variants in rhesus monkeys.defining the earliest virologic events following human immunodeficiency virus type 1 (hiv-1) transmission may be critical for the design of vaccine strategies aimed at blocking acquisition of hiv-1 infection. in particular, the length of the eclipse phase and the number of transmitted virus variants may define the window in which a prophylactic vaccine must act. here we show that the dose of the virus inoculum affects these key virologic parameters following intrarectal simian immunodeficiency v ...201020686016
envelope-modified single-cycle simian immunodeficiency virus selectively enhances antibody responses and partially protects against repeated, low-dose vaginal challenge.immunization of rhesus macaques with strains of simian immunodeficiency virus (siv) that are limited to a single cycle of infection elicits t-cell responses to multiple viral gene products and antibodies capable of neutralizing lab-adapted siv, but not neutralization-resistant primary isolates of siv. in an effort to improve upon the antibody responses, we immunized rhesus macaques with three strains of single-cycle siv (scsiv) that express envelope glycoproteins modified to lack structural feat ...201020702641
emergence of simian immunodeficiency virus-specific cytotoxic cd4+ t cells and increased humoral responses correlate with control of rebounding viremia in cd8-depleted macaques infected with rev-independent live-attenuated simian immunodeficiency virus.indian rhesus macaques infected with the rev-independent live-attenuated sivmac239 strains control viremia to undetectable levels, have persistent but low cellular and humoral anti-siv responses, and show no signs of immune deficiency. to analyze the immune mechanisms responsible for viral control, five macaques infected at day 1 after birth were subjected to cd8(+) cell depletion at 6.7 y postinfection. this resulted in viremia increases to 3.7-5.5 log(10) rna copies, supporting a role of cd8-m ...201020702730
macaques vaccinated with simian immunodeficiency virus sivmac239delta nef delay acquisition and control replication after repeated low-dose heterologous siv challenge.an effective human immunodeficiency virus (hiv) vaccine will likely need to reduce mucosal transmission and, if infection occurs, control virus replication. to determine whether our best simian immunodeficiency virus (siv) vaccine can achieve these lofty goals, we vaccinated eight indian rhesus macaques with sivmac239delta nef and challenged them intrarectally (i.r.) with repeated low doses of the pathogenic heterologous swarm isolate sivsme660. we detected a significant reduction in acquisition ...201020592091
impact of short-term combined antiretroviral therapy on brain virus burden in simian immunodeficiency virus-infected and cd8+ lymphocyte-depleted rhesus macaques.antiretroviral drugs suppress virus burden in the cerebrospinal fluid of hiv-infected individuals; however, the direct effect of antiretrovirals on virus replication in brain parenchyma is poorly understood. we investigated the effect of short-term combined antiretroviral therapy (cart) on brain virus burden in rhesus monkeys using the cd8-depletion model of accelerated simian immunodeficiency virus (siv) encephalitis. four monkeys received cart (consisting of the nonpenetrating agents pmpa and ...201020595631
fundamental difference in the content of high-mannose carbohydrate in the hiv-1 and hiv-2 lineages.the virus-encoded envelope proteins of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) typically contain 26 to 30 sites for n-linked carbohydrate attachment. n-linked carbohydrate can be of three major types: high mannose, complex, or hybrid. the lectin proteins from galanthus nivalis (gna) and hippeastrum hybrid (hha), which specifically bind high-mannose carbohydrate, were found to potently inhibit the replication of a pathogenic cloned siv from rhesus macaques, sivm ...201020610711
generation of a dual rt env shiv that is infectious in rhesus macaques.the best current animal model for hiv infection and evaluation of antiviral compounds is the simian-human immunodeficiency virus (shiv)/macaque system. there are multiple recombinant shivs available, but these viruses have limitations in evaluating combination drug strategies for prevention. drug combinations that target reverse transcriptase (rt, either nrti or nnrti) and envelope (entry or fusion inhibitors) have to be tested separately, which does not permit the assessment of additive, synerg ...201020618587
microbial translocation in simian immunodeficiency virus (siv)-infected rhesus monkeys (macaca mulatta).chronic immune activation is a hallmark of hiv infection and has been postulated as major factor in the pathogenesis of aids. recent evidence suggests that activation of immune cells is triggered by microbial translocation through the impaired gastrointestinal barrier.201020618590
increased cd4+ t cell levels during il-7 administration of antiretroviral therapy-treated simian immunodeficiency virus-positive macaques are not dependent on strong proliferative responses.cd4(+) t cell depletion is a fundamental component of hiv infection and aids pathogenesis and is not always reversed following antiretroviral therapy (art). in this study, the siv-infected rhesus macaque model was used to assess recombinant simian il-7 in its glycosylated form (rsil-7gly) to enhance regeneration of cd4(+) t cells, particularly the crucial central memory compartment, after art. we assessed the impact of rsil-7gly administration as single injections and as a cluster of three doses ...201020622118
clonal repertoires of virus-specific cd8+ t lymphocytes are shared in mucosal and systemic compartments during chronic simian immunodeficiency virus infection in rhesus monkeys.because it is thought that mucosal tissues play a fundamental role in early hiv/siv infection, it is crucial to understand the virus-specific responses in mucosal tissues to facilitate devising strategies to prevent and control these infections. we have employed tcr repertoire analyses to define the clonal composition of a dominant siv epitope-specific cd8(+) t cell population in mucosal and systemic compartments of siv-infected rhesus monkeys during both acute and chronic infection. we show tha ...201020624939
heightened cytotoxic responses and impaired biogenesis contribute to early pathogenesis in the oral mucosa of simian immunodeficiency virus-infected rhesus macaques.simian immunodeficiency virus (siv) infection disseminated into the oropharyngeal tissues of rhesus macaques 6 weeks following intravenous inoculation. severe local cd4(+) t-cell depletion coincided with increases in nk cell and proinflammatory biomarkers and the disruption of growth-associated gene transcription, demonstrating the rapid establishment of pathogenesis in the oral mucosa.200919091994
antiviral cd8+ t cells in the genital tract control viral replication and delay progression to aids after vaginal siv challenge in rhesus macaques immunized with virulence attenuated shiv 89.6.the recently failed clinical efficacy trial of an acquired immunodeficiency syndrome (aids) vaccine that elicits antiviral cd8(+) t-cell responses has emphasized the challenge of producing an effective vaccine against human immunodeficiency virus (hiv). in the simian immunodeficiency virus (siv)/ rhesus monkey model of aids, live-attenuated lentivirus 'vaccines' provide the best protection from uncontrolled viral replication and clinical disease after pathogenic siv challenge. this review summar ...200919093961
characterization of 47 mhc class i sequences in filipino cynomolgus macaques.cynomolgus macaques (macaca fascicularis) provide increasingly common models for infectious disease research. several geographically distinct populations of these macaques from southeast asia and the indian ocean island of mauritius are available for pathogenesis studies. though host genetics may profoundly impact results of such studies, similarities and differences between populations are often overlooked. in this study we identified 47 full-length mhc class i nucleotide sequences in 16 cynomo ...200919107381
partial protection of simian immunodeficiency virus (siv)-infected rhesus monkeys against superinfection with a heterologous siv isolate.although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (hiv-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. we explored these questions in the simian immunodeficiency virus (siv)/rhesus monkey model of hiv-1/aids. we infected cohorts of rhesus monkeys with either sivmac251 or ...200919129440
high specific infectivity of plasma virus from the pre-ramp-up and ramp-up stages of acute simian immunodeficiency virus infection.to define the ratio of simian immunodeficiency virus (siv) rna molecules to infectious virions in plasma, a ramp-up-stage plasma pool was made from the earliest viral rna (vrna)-positive plasma samples (collected approximately 7 days after inoculation) from seven macaques, and a set-point-stage plasma pool was made from plasma samples collected 10 to 16 weeks after peak viremia from seven macaques; vrna levels in these plasma pools were determined, and serial 10-fold dilutions containing 1 to 1, ...200919129448
simian immunodeficiency virus types 1 and 2 (siv mnd 1 and 2) have different pathogenic potentials in rhesus macaques upon experimental cross-species transmission.the mandrill (mandrillus sphinx) is naturally infected by two types of simian immunodeficiency virus (siv): sivmnd types 1 and 2. both of these viruses cause long-term, non-progressive infections in their natural host despite high plasma viral loads. this study assessed the susceptibility of rhesus macaques to infection by these two types of sivmnd and compared the virological and basic immunological characteristics of the resulting infections with those observed in natural infection in mandrill ...200919141460
a case for innate immune effector mechanisms as contributors to disease resistance in siv-infected sooty mangabeys.natural or experimental infection of the african sooty mangabey (sm) with the simian immunodeficiency virus (siv) results in chronic high levels of virus replication but is associated with none of the debilitating immunopathology, including the marked cd4 t-cell depletion, persistent cell activation and acquired immunodeficiency, that afflicts non-natural hosts such as siv-infected asian rhesus macaques (rm) and hiv-infected humans. although siv-infected rm have served as important models of aid ...200919149550
glycerol monolaurate prevents mucosal siv transmission.although there has been great progress in treating human immunodeficiency virus 1 (hiv-1) infection, preventing transmission has thus far proven an elusive goal. indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission. nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (siv)-rhesus macaque (macacca mulatta) model point to opportunities at the earliest stages o ...200919262509
decreased nk cell frequency and function is associated with increased risk of kir3dl allele polymorphism in simian immunodeficiency virus-infected rhesus macaques with high viral loads.nk cells have been established as an important effector of innate immunity in a variety of viral infections. in hiv-1 infection in humans, alterations of nk cell function, frequency, and expression of various nk receptors have been reported to be associated with differential dynamics of disease progression. expression of certain alleles of kir3dl and kir3ds receptors on nk cells was shown to correlate with levels of virus replication. in the siv-infected rhesus macaque (rm) model of aids, severa ...200919265142
rhesus macaque model of chronic opiate dependence and neuro-aids: longitudinal assessment of auditory brainstem responses and visual evoked potentials.our work characterizes the effects of opiate (morphine) dependence on auditory brainstem and visual evoked responses in a rhesus macaque model of neuro-aids utilizing a chronic continuous drug delivery paradigm. the goal of this study was to clarify whether morphine is protective, or if it exacerbates simian immunodeficiency virus (siv)-related systemic and neurological disease. our model employs a macrophage tropic cd4/ccr5 coreceptor virus, siv(mac)239 (r71/e17), which crosses the blood-brain ...200919283490
evaluation of the lymphocyte trafficking drug fty720 in shivsf162p3-infected rhesus macaques.fty720 causes retention of lymphocytes in lymphatic tissues. previous studies revealed that fty720 can decrease or eliminate chronic viral infections of mice. we address here whether therapeutic use of fty720 in simian human immunodeficiency virus (shiv)-infected rhesus macaques could also decrease viraemia.200919218272
acute-phase cd4+ t-cell proliferation and cd152 upregulation predict set-point virus replication in vaccinated simian-human immunodeficiency virus strain 89.6p-infected macaques.human immunodeficiency virus (hiv) infection in humans and simian immunodeficiency virus (siv) infection in macaques are accompanied by a combined early loss of ccr5 (cd195)-expressing cd4(+) memory t cells, loss of t-helper function and t-cell hyperactivation, which have all been associated with development of high virus load and disease progression. here, a cohort of vaccinated simian-human immunodeficiency virus strain 89.6p (shiv(89.6p))-infected rhesus macaques, where preferential depletion ...200919223489
enhanced antibody responses elicited by a cpg adjuvant do not improve the protective effect of an aldrithiol-2-inactivated simian immunodeficiency virus therapeutic aids vaccine.the potential benefit of using unmethylated cpg oligoribodeoxynucleotides (odn) as an adjuvant in a therapeutic simian immunodeficiency virus (siv) vaccine consisting of at2-inactivated sivmac239 was evaluated in siv-infected rhesus macaques receiving antiretroviral therapy (art). we hypothesized that using cpg odn as an adjuvant in therapeutic vaccination would enhance siv-specific immune responses and suppress siv replication after art was stopped. to test our hypothesis, we immunized chronica ...200919225080
passive immunization with human neutralizing monoclonal antibodies against hiv-1 in macaque models: experimental approaches.after more than 20 years of intense research, a safe and effective vaccine against hiv-1/aids has not been developed. passive immunization has been used as a tool to demonstrate the role of neutralizing antibodies in conferring protection against hiv-1 challenge in chimpanzees. because these animals are endangered and studies are difficult to conduct with this species, chimeric viruses, termed simian-human immunodeficiency viruses (shivs), have been generated that encode the hiv-1 envelope gene ...200919252837
vaccine-induced, simian immunodeficiency virus-specific cd8+ t cells reduce virus replication but do not protect from simian immunodeficiency virus disease progression.our limited understanding of the interaction between primate lentiviruses and the host immune system complicates the design of an effective hiv/aids vaccine. to identify immunological correlates of protection from siv disease progression, we immunized two groups of five rhesus macaques (rms) with either modified vaccinia ankara (mva) or mvadeltaudg vectors that expressed sivmac239 gag and tat. both vectors raised a siv-specific cd8(+) t cell response, with a magnitude that was greater in mucosal ...200919542473
role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (siv) in macaques vaccinated with replication-deficient viral vectors.we investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (sciv) encoding siv antigens combined with adeno5-siv or sciv pseudotyped with murine leukemia virus envelope boosting strategies. the vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens.200919545395
protective efficacy of a single immunization of a chimeric adenovirus vector-based vaccine against simian immunodeficiency virus challenge in rhesus monkeys.rare serotype and chimeric recombinant adenovirus (rad) vectors that evade anti-ad5 immunity are currently being evaluated as potential vaccine vectors for human immunodeficiency virus type 1 and other pathogens. we have recently reported that a heterologous rad prime-boost regimen expressing simian immunodeficiency virus (siv) gag afforded durable partial immune control of an siv challenge in rhesus monkeys. however, single-shot immunization may ultimately be preferable for global vaccine deliv ...200919553307
effector memory t cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge.the rapid onset of massive, systemic viral replication during primary hiv or simian immunodeficiency virus (siv) infection and the immune evasion capabilities of these viruses pose fundamental problems for vaccines that depend upon initial viral replication to stimulate effector t cell expansion and differentiation. we hypothesized that vaccines designed to maintain differentiated effector memory t cell (tem cell) responses at viral entry sites might improve efficacy by impairing viral replicati ...200919219024
recombinant mycobacterium bovis bcg prime-recombinant adenovirus boost vaccination in rhesus monkeys elicits robust polyfunctional simian immunodeficiency virus-specific t-cell responses.while mycobacteria have been proposed as vaccine vectors because of their persistence and safety, little has been done systematically to optimize their immunogenicity in nonhuman primates. we successfully generated recombinant mycobacterium bovis bcg (rbcg) expressing simian immunodeficiency virus (siv) gag and pol as multigenic, nonintegrating vectors, but rbcg-expressing siv env was unstable. a dose and route determination study in rhesus monkeys revealed that intramuscular administration of r ...200919297477
polyfunctional cd4+ t-cell induction in neutralizing antibody-triggered control of simian immunodeficiency virus infection.rapid depletion of memory cd4(+) t cells and delayed induction of neutralizing antibody (nab) responses are characteristics of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) infections. although it was speculated that postinfection nab induction could have only a limited suppressive effect on primary hiv replication, a recent study has shown that a single passive nab immunization of rhesus macaques 1 week after siv challenge can result in reduction of viral loads at t ...200919297503
improved survival in rhesus macaques immunized with modified vaccinia virus ankara recombinants expressing simian immunodeficiency virus envelope correlates with reduction in memory cd4+ t-cell loss and higher titers of neutralizing antibody.previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (siv) gag-pol and env recombinants of the attenuated poxvirus modified vaccinia virus ankara (mva) provided protection from high viremia and aids following challenge with a pathogenic strain of siv. although all animals became infected, plasma viremia was significantly reduced in animals that received the mva-siv recombinant vaccines compared with animals that received nonrecombinant mva. most importan ...200919321617
sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with siv lentiviral vector-transduced cd34+ cells.we previously reported that lentiviral vectors derived from the simian immunodeficiency virus (siv) were efficient at transducing rhesus hematopoietic repopulating cells. to evaluate the persistence of vector-containing and -expressing cells long term, and the safety implications of siv lentiviral vector-mediated gene transfer, we followed 3 rhesus macaques for more than 4 years after transplantation with transduced cd34+ cells. all 3 animals demonstrated significant vector marking and expressio ...200919339698
genetically modified cd34+ hematopoietic stem cells contribute to turnover of brain perivascular macrophages in long-term repopulated primates.studies in rodents have shown that brain perivascular macrophages are derived from bone marrow precursors. less is known about the origin and turnover of perivascular cells in the human central nervous system. we took advantage of non-human primates reconstituted with autologous cd34+ hematopoietic stem cells that had been transduced with a lentiviral vector expressing the enhanced green fluorescent protein (egfp) to study the ontogeny of brain macrophages of rhesus macaques. flow cytometry and ...200919349370
association of progressive cd4(+) t cell decline in siv infection with the induction of autoreactive antibodies.the progressive decline of cd4(+) t cells is a hallmark of disease progression in human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) infection. whereas the acute phase of the infection is dominated by virus-mediated depletion of memory cd4(+) t cells, chronic infection is often associated with a progressive decline of total cd4(+) t cells, including the naïve subset. the mechanism of this second phase of cd4(+) t cell loss is unclear and may include immune activation-indu ...200919360097
interleukin-18 predicts atherosclerosis progression in siv-infected and uninfected rhesus monkeys (macaca mulatta) on a high-fat/high-cholesterol diet.interleukin (il)-18 levels have been identified as important predictors of cardiovascular mortality and are often elevated in human immunodeficiency virus (hiv)-infected individuals. to investigate a possible function for il-18 in atherogenesis in the context of early hiv infection, we used the simian immunodeficiency model of hiv infection. acutely simian immunodeficiency virus-infected and uninfected rhesus monkeys (macaca mulatta) on an atherogenic diet were evaluated prospectively for athero ...200919381133
the level of monocyte turnover predicts disease progression in the macaque model of aids.it is widely accepted that destruction of cd4(+) t cells and viral load are the primary markers for immunodeficiency in hiv-1-infected humans and in simian immunodeficiency virus (siv)-infected macaques. however, monocyte/macrophages are also important targets of hiv/siv infection and a critical link between innate and adaptive immunity. we therefore examined whether changes in cells of the monocyte/macrophage lineage could be linked to the pathogenesis of aids in the rhesus macaque model. here, ...200919383966
construction of soluble mamu-b*1703, a class i major histocompatibility complex of chinese rhesus macaques, monomer and tetramer loaded with a simian immunodeficiency virus peptide.chinese-descent rhesus macaques have become more prevalent for hiv infection and vaccine investigation than indian-origin macaques. most of the currently available data and reagents such as major histocompatibility complex (mhc) class i tetramers, however, were derived from indian-origin macaques due to the dominant use of these animals in history. although there are significant differences in the immunogenetic background between the two macaque populations, they share a few of common mhc class ...200919403061
low-dose rectal inoculation of rhesus macaques by sivsme660 or sivmac251 recapitulates human mucosal infection by hiv-1.we recently developed a novel strategy to identify transmitted hiv-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. here, we used this approach to determine the molecular features of simian immunodeficiency virus (siv) transmission in 18 experimentally infected indian rhesus macaques. animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of sivmac251 or sivsme660 that exhibited sequence diversity typical of e ...200919414559
high frequencies of resting cd4+ t cells containing integrated viral dna are found in rhesus macaques during acute lentivirus infections.we and others have reported that the vast majority of virus-producing cd4(+) t cells during the acute infection of rhesus macaques with simian immunodeficiency virus (siv) or cxcr4 (x4)-using simian/human immunodeficiency viruses (shivs) exhibited a nonactivated phenotype. these findings have been extended to show that resting cd4(+) t lymphocytes collected from siv- or x4-shiv-infected animals during the first 10 days of infection continue to release virus ex vivo. furthermore, we observed high ...200919416840
initiation of antiretroviral therapy 48 hours after infection with simian immunodeficiency virus potently suppresses acute-phase viremia and blocks the massive loss of memory cd4+ t cells but fails to prevent disease.we investigated whether a 28-day course of potent antiretroviral therapy, initiated at a time point (48 h postinoculation) following simian immunodeficiency virus (siv) inoculation when the acquisition of a viral infection was virtually assured, would sufficiently sensitize the immune system and result in controlled virus replication when treatment was stopped. the administration of tenofovir 48 h after siv inoculation to six mamu-a*01-negative rhesus macaques did, in fact, potently suppress vir ...200919420078
genetic engineering of a modified herpes simplex virus 1 vaccine vector.the herpes simplex virus 1 (hsv-1) d106 mutant virus is a multiple immediate-early gene deletion mutant virus that has been effective as an aids vaccine vector in rhesus macaques (kaur a, sanford hb, garry d, lang s, klumpp sa, watanabe d, et al. ability of herpes simplex virus vectors to boost immune responses to dna vectors and to protect against challenge by simian immunodeficiency virus. virology 2007;357:199-214). further analysis of this vector is needed to advance development into clinica ...200919428888
early antiretroviral treatment prevents the development of central nervous system abnormalities in simian immunodeficiency virus-infected rhesus monkeys.neurocognitive disorders are devastating consequences of hiv infection. although antiretroviral regimens have been efficacious in both improving life expectancy and decreasing dementia, there has not been an effect on the overall prevalence of hiv-associated neurocognitive disorders. whether early institution of treatment, or treatment with drugs that effectively penetrate the blood-brain barrier, would help protect from such conditions is not known. using the simian immunodeficiency virus/macaq ...200919455015
is the gut the major source of virus in early simian immunodeficiency virus infection?the acute phases of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) infection are characterized by rapid and profound depletion of cd4+ t cells from the guts of infected individuals. the large number of cd4+ t cells in the gut (a large fraction of which are activated and express the hiv/siv coreceptor ccr5), the high level of infection of these cells, and the temporal coincidence of this cd4+ t-cell depletion with the peak of virus in plasma in acute infection suggest ...200919458001
treatment with anti-fasl antibody preserves memory lymphocytes and virus-specific cellular immunity in macaques challenged with simian immunodeficiency virus.immune deficiency viruses such as siv in macaques or hiv-1 in human beings have evolved mechanisms to defeat host immunity that also impact the efficacy of vaccines. a key factor for vaccine protection is whether immune responses elicited by prior immunization remain at levels sufficient to limit disease progression once a host is exposed to the pathogen. one potential mechanism for escaping pre-existing immunity is to trigger death among antigen-activated cells. we tested whether fasl/cd178 is ...200919498020
development of a human immunodeficiency virus type 1-based lentiviral vector that allows efficient transduction of both human and rhesus blood cells.human immunodeficiency virus type 1 (hiv-1) vectors transduce rhesus blood cells poorly due to a species-specific block by trim5alpha and apobec3g, which target hiv-1 capsid and viral infectivity factor (vif), respectively. we sought to develop a lentiviral vector capable of transducing both human and rhesus blood cells by combining components of both hiv-1 and simian immunodeficiency virus (siv), including siv capsid (sca) and siv vif. a chimeric hiv-1 vector including sca (chihiv) was superior ...200919625395
dominant cd8+ t-lymphocyte responses suppress expansion of vaccine-elicited subdominant t lymphocytes in rhesus monkeys challenged with pathogenic simian-human immunodeficiency virus.emerging data suggest that a cytotoxic t-lymphocyte response against a diversity of epitopes confers greater protection against a human immunodeficiency virus/simian immunodeficiency virus infection than does a more focused response. to facilitate the creation of vaccine strategies that will generate cellular immune responses with the greatest breadth, it will be important to understand the mechanisms employed by the immune response to regulate the relative magnitudes of dominant and nondominant ...200919641002
profound cd4+/ccr5+ t cell expansion is induced by cd8+ lymphocyte depletion but does not account for accelerated siv pathogenesis.depletion of cd8(+) lymphocytes during acute simian immunodeficiency virus (siv) infection of rhesus macaques (rms) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for cd8(+) lymphocytes in determining postacute-phase viral replication set points. however, we report that cd8(+) lymphocyte depletion is also associated with a dramatic induction of proliferation among cd4(+) effector memory t (t(em)) cells and, to a le ...200919546246
susceptibility to simian immunodeficiency virus ex vivo predicts outcome of a prime-boost vaccine after sivmac239 challenge.efficacy assessment of aids vaccines relies both on preclinically challenging immunized monkeys with simian immunodeficiency virus (siv) or monitoring infection rates in large human trials. although conventional parameters of vaccine-induced immune responses do not completely predict outcome, existing methods for testing cellular immunity are sophisticated and difficult to establish in resource-limited settings.200919644382
modification of a loop sequence between alpha-helices 6 and 7 of virus capsid (ca) protein in a human immunodeficiency virus type 1 (hiv-1) derivative that has simian immunodeficiency virus (sivmac239) vif and ca alpha-helices 4 and 5 loop improves replication in cynomolgus monkey cells.human immunodeficiency virus type 1 (hiv-1) productively infects only humans and chimpanzees but not cynomolgus or rhesus monkeys while simian immunodeficiency virus isolated from macaque (sivmac) readily establishes infection in those monkeys. several hiv-1 and sivmac chimeric viruses have been constructed in order to develop an animal model for hiv-1 infection. construction of an hiv-1 derivative which contains sequences of a sivmac239 loop between alpha-helices 4 and 5 (l4/5) of capsid protei ...200919650891
effect of b-cell depletion on viral replication and clinical outcome of simian immunodeficiency virus infection in a natural host.simian immunodeficiency virus (siv)-infected african nonhuman primates do not progress to aids in spite of high and persistent viral loads (vls). some authors consider the high viral replication observed in chronic natural siv infections to be due to lower anti-siv antibody titers than those in rhesus macaques, suggesting a role of antibodies in controlling viral replication. we therefore investigated the impact of antibody responses on the outcome of acute and chronic sivagm replication in afri ...200919656874
systemic and mucosal t-lymphocyte activation induced by recombinant adenovirus vaccines in rhesus monkeys.the administration of vectors designed to elicited cell-mediated immune responses may have other consequences that are clinically significant. to explore this possibility, we evaluated t-cell activation during the first 2 months after recombinant adenovirus serotype 5 (rad5) prime or boost immunizations in rhesus monkeys. we also evaluated the kinetics of t-lymphocyte activation in both the systemic and the mucosal compartments after rad5 administration in monkeys with preexisting immunity to ad ...200919656883
infection with "escaped" virus variants impairs control of simian immunodeficiency virus sivmac239 replication in mamu-b*08-positive macaques.an understanding of the mechanism(s) by which some individuals spontaneously control human immunodeficiency virus (hiv)/simian immunodeficiency virus replication may aid vaccine design. approximately 50% of indian rhesus macaques that express the major histocompatibility complex (mhc) class i allele mamu-b*08 become elite controllers after infection with simian immunodeficiency virus sivmac239. mamu-b*08 has a binding motif that is very similar to that of hla-b27, a human mhc class i allele asso ...200919726517
nasal dna-mva siv vaccination provides more significant protection from progression to aids than a similar intramuscular vaccination.preventive human immunodeficiency virus (hiv) vaccination may require induction of virus-specific immune responses at mucosal sites to contain viral infection locally after exposure, as most hiv infections occur through mucosal surfaces. we compared the efficacy of an intranasal or intramuscular simian immunodeficiency virus (siv)+ interleukin (il)-2+il-15 dna/siv-mva (modified vaccinia virus ankara) vaccination in preventing disease progression in sivmac251 intrarectally challenged rhesus macaq ...200919741603
interactions between sivnef, sivgagpol and alix correlate with viral replication and progression to aids in rhesus macaques.infection with simian immunodeficiency virus (siv) leads to high viral loads and progression to simian aids (saids) in rhesus macaques. the viral accessory protein nef is required for this phenotype in monkeys as well as in hiv-infected humans. previously, we determined that hivnef binds hivgagpol and alix for optimal viral replication in cells. in this study, we demonstrated that these interactions could correlate with high viral loads leading to saids in the infected host. by infecting rhesus ...200919748111
effect of therapeutic immunization using ad5/35 and mva vectors on siv infection of rhesus monkeys undergoing antiretroviral therapy.antiretroviral therapy (art) effectively slows the progression of aids. however, drug resistance and/or toxicity can limit the utility of art in many patients. in this study, we assessed whether a viral vector-based vaccine can be used as a therapeutic vaccine in simian immunodeficiency virus (siv)-infected monkeys. the effect of vaccinating sivmac239-infected rhesus monkeys with an siv gag and gp120-expressing adenovirus (ad) vector vaccine and a modified vaccinia ankara (mva) vaccine was explo ...200918923453
immunization with single-cycle siv significantly reduces viral loads after an intravenous challenge with siv(mac)239.strains of simian immunodeficiency virus (siv) that are limited to a single cycle of infection were evaluated for the ability to elicit protective immunity against wild-type siv(mac)239 infection of rhesus macaques by two different vaccine regimens. six animals were inoculated at 8-week intervals with 6 identical doses consisting of a mixture of three different envelope variants of single-cycle siv (scsiv). six additional animals were primed with a mixture of cytoplasmic domain-truncated envelop ...200919165322
co-immunization with il-15 enhances cellular immune responses induced by a vif-deleted simian immunodeficiency virus proviral dna vaccine and confers partial protection against vaginal challenge with sivmac251.simian immunodeficiency virus (siv) infection of rhesus macaques is a valuable animal model for human immunodeficiency virus (hiv)-1 vaccine development. our laboratory recently described the immunogenicity and limited efficacy of a vif-deleted sivmac239 proviral dna (siv/cmvdelta vif) vaccine. the current report characterizes immunogenicity and efficacy for the siv/cmvdelta vif proviral dna vaccine when co-inoculated with an optimized rhesus interleukin (ril)-15 expression plasmid. macaques co- ...200919193388
probable deceleration of progression of simian aids affected by opiate dependency: studies with a rhesus macaque/sivsmm9 model.to determine effects of opiate dependency on development of simian aids.200919194320
bone marrow-based homeostatic proliferation of mature t cells in nonhuman primates: implications for aids pathogenesis.bone marrow (bm) is the key hematopoietic organ in mammals and is involved in the homeostatic proliferation of memory cd8(+) t cells. here we expanded on our previous observation that bm is a preferential site for t-cell proliferation in simian immunodeficiency virus (siv)-infected sooty mangabeys (sms) that do not progress to aids despite high viremia. we found high levels of mature t-cell proliferation, involving both naive and memory cells, in healthy sms and rhesus macaques (rms). in additio ...200918832134
correlation of vaccine-elicited systemic and mucosal nonneutralizing antibody activities with reduced acute viremia following intrarectal simian immunodeficiency virus sivmac251 challenge of rhesus macaques.cell-mediated immunity and neutralizing antibodies contribute to control of human immunodeficiency virus/simian immunodeficiency virus (hiv/siv) infection, but the role of nonneutralizing antibodies is not defined. previously, we reported that sequential oral/oral or intranasal/oral (i/o) priming with replication-competent adenovirus type 5 host range mutant (ad5hr)-siv recombinants, followed by intramuscular envelope protein boosting, elicited systemic and mucosal cellular immunity and exhibite ...200918971271
antiretroviral activity of the aminothiol wr1065 against human immunodeficiency virus (hiv-1) in vitro and simian immunodeficiency virus (siv) ex vivo.wr1065 is the free-thiol metabolite of the cytoprotective aminothiol amifostine, which is used clinically at very high doses to protect patients against toxicity induced by radiation and chemotherapy. in an earlier study we briefly reported that the aminothiol wr1065 also inhibits hiv-1 replication in phytohemagglutinin (pha)-stimulated human t-cell blasts (tcbs) infected in culture for 2 hr before wr1065 exposure. in this study we expanded the original observations to define the dose-response c ...200919895691
simian immunodeficiency virus envelope glycoprotein counteracts tetherin/bst-2/cd317 by intracellular sequestration.tetherin is an ifn-inducible restriction factor that inhibits hiv-1 particle release in the absence of the hiv-1 countermeasure, viral protein u (vpu). although ubiquitous in hiv-1 and simian immunodeficiency viruses from chimpanzees, greater spot nosed monkeys, mustached monkeys, and mona monkeys, other primate lentiviruses do not encode a vpu protein. here we demonstrate that siv from tantalus monkeys (sivtan) encodes an envelope glycoprotein (sivtan env) able to counteract tetherin from tanta ...200919864625
elevated levels of innate immune modulators in lymph nodes and blood are associated with more-rapid disease progression in simian immunodeficiency virus-infected monkeys.cytokines and chemokines are critical for establishing tissue-specific immune responses and play key roles in modulating disease progression in simian immunodeficiency virus (siv)-infected macaques and human immunodeficiency virus (hiv)-infected humans. the goal here was to characterize the innate immune response at different tissue sites and to correlate these responses to clinical outcome, initially focusing on rhesus macaques orally inoculated with siv and monitored until onset of simian aids ...200919759147
an integrated systems analysis implicates egr1 downregulation in simian immunodeficiency virus encephalitis-induced neural dysfunction.human immunodeficiency virus (hiv)-associated dementia (had) is a syndrome occurring in hiv-infected patients with advanced disease that likely develops as a result of macrophage and microglial activation as well as other immune events triggered by virus in the central nervous system. the most relevant experimental model of had, rhesus macaques exhibiting simian immunodeficiency virus (siv) encephalitis (sive), closely reproduces the human disease and has been successfully used to advance our un ...200919812322
[purification, crystallographic analysis of rhesus mhc-i mamu-a*02 complexed with simian immunodeficiency virus nonapeptide].rhesus macaque (macaca mulatta) is the best model to study of human immunodeficiency virus (hiv) infection and to develop acquired immunodeficiency syndrome (aids) vaccine. the crystal structure of its major histocompatibility antigen complex (mhc) is helpful to understand the mechanism of hiv immune evasion. in this study, we cloned the light chain (beta2m) of mhc class i allele of rhesus macaques, mamu-a*02, and inserted it into pet21a(+) vector. we transfected the recombinant plasmid pet21a(+ ...200919835144
viral interleukin-6 encoded by rhesus macaque rhadinovirus is associated with lymphoproliferative disorder (lpd).rhesus macaques (rm) co-infected with simian immunodeficiency virus (siv) and rhesus macaque rhadinovirus (rrv) develop abnormal cellular proliferations characterized as extra-nodal lymphoma and retroperitoneal fibromatosis (rf). rrv encodes a viral interleukin-6 (vil-6), much like kaposi's sarcoma-associated herpesvirus, and involvement of the viral cytokine was examined in proliferative lesions.200919863672
anti-retroviral therapy fails to restore the severe th-17: tc-17 imbalance observed in peripheral blood during simian immunodeficiency virus infection.human immuno deficiency virus and simian immunodeficiency virus infections are characterized by a severe loss of th-17 cells (il-17(+)cd4(+) t cells) that has been associated with disease progression and systemic dissemination of bacterial infections. anti-retroviral therapy (art) has led to repopulation of cd4(+) t cells in peripheral tissues with little sustainable repopulation in mucosal tissues. given the central importance of th-17 cells in mucosal homeostasis, it is not known if the failur ...200919863676
impact of cytotoxic-t-lymphocyte memory induction without virus-specific cd4+ t-cell help on control of a simian immunodeficiency virus challenge in rhesus macaques.despite many efforts to develop aids vaccines eliciting virus-specific t-cell responses, whether induction of these memory t cells by vaccination before human immunodeficiency virus (hiv) exposure can actually contribute to effective t-cell responses postinfection remains unclear. in particular, induction of hiv-specific memory cd4(+) t cells may increase the target cell pool for hiv infection because the virus preferentially infects hiv-specific cd4(+) t cells. however, virus-specific cd4(+) he ...200919587045
novel translation products from simian immunodeficiency virus sivmac239 env-encoding mrna contain both rev and cryptic t-cell epitopes.understanding the correlates of immune protection against human immunodeficiency virus and simian immunodeficiency virus (siv) will require defining the entire cellular immune response against the viruses. here, we define two novel translation products from the siv env mrna that are targeted by the t-cell response in siv-infected rhesus macaques. the shorter product is a subset of the larger product, which contains both the first exon of the rev protein and a translated portion of the rev intron ...200919605480
derivation and characterization of a simian immunodeficiency virus sivmac239 variant with tropism for cxcr4.like human immunodeficiency virus type 1 (hiv-1), most simian immunodeficiency virus (siv) strains use ccr5 to establish infection. however, while hiv-1 can acquire the ability to use cxcr4, sivs that utilize cxcr4 have rarely been reported. to explore possible barriers against siv coreceptor switching, we derived an r5x4 variant, termed 239-st1, from the r5 clone sivmac239 by serially passaging virus in cd4(+) cxcr4(+) ccr5(-) supt1 cells. a 239-st1 env clone, designated 239-st1.2-32, used cxcr ...200919605489
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