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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
differential cell surface expression of rhesus macaque's major histocompatibility complex class i alleles mamu-b*1703 and mamu-b*0101.the major histocompatibility complex class i allele mamu-b*17 of rhesus macaques is an elite controller of simian immunodeficiency virus (siv) infection whereas mamu-b*01 has no inhibitory effect on siv replication. the mechanism is still elusive. in this study, the so-called "missing g" in the leading peptide sequence of mamu-b*1703 allele was artificially inserted back through pcr amplification, and the new sequence was renamed as mamu-b*1703(+g). the plasmids harboring mamu-b*1703, mamu-b*170 ...201020383467
antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in mf59 adjuvant.we have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus shiv(sf162p4) following sequential immunization with alphavirus replicon particles (vrp) of a chimeric recombinant vee/sin alphavirus (derived from venezuelan equine encephalitis virus [vee] and the sindbis virus [sin]) encoding human immunodeficiency virus type 1 hiv-1(sf162) gp140deltav2 envelope (env) and trimeric env protein in mf59 adjuvant ...201020392857
variability in a dominant block to siv early reverse transcription in rhesus monkey cells predicts in vivo viral replication and time to death.while it has long been appreciated that there is considerable variability in host containment of hiv/siv replication, the determinants of that variability are not fully understood. previous studies demonstrated that the degree of permissivity of a macaque's peripheral blood mononuclear cells (pbmc) for infection with simian immunodeficiency virus (siv) in vitro predicted that animal's peak plasma virus rna levels following siv infection in vivo. the present study was conducted to define the mech ...201020416115
frequency of the major histocompatibility complex mamu-a*01 allele in experimental rhesus macaques in china.in indian rhesus macaques, the major histocompatibility complex mamu gene, especially the mamu-a*01 allele, plays an important role in simian immunodeficiency virus susceptibility and disease progression. the mamu-a*01 allele is one of the protective genes mostly being studied in simian acquired immunodeficiency syndrome.201020444001
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
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
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
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
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
diversity of mhc class i genes in burmese-origin rhesus macaques.rhesus macaques (macaca mulatta) are widely used in developing a strategy for vaccination against human immunodeficiency virus by using simian immunodeficiency virus infection as a model system. because the genome diversity of major histocompatibility complex (mhc) is well known to control the immune responsiveness to foreign antigens, mhc loci in indian- and chinese-origin macaques used in the experiments have been characterized, and it was revealed that the diversity of mhc in macaques was lar ...201020640416
recombinant varicella vaccines induce neutralizing antibodies and cellular immune responses to siv and reduce viral loads in immunized rhesus macaques.the development of an effective aids vaccine remains one of the highest priorities in hiv research. the live, attenuated varicella-zoster virus (vzv) oka vaccine, safe and effective for prevention of chickenpox and zoster, also has potential as a recombinant vaccine against other pathogens, including human immunodeficiency virus (hiv). the simian varicella model, utilizing simian varicella virus (svv), offers an approach to evaluate recombinant varicella vaccine candidates. recombinant svv (rsvv ...201020654666
mechanisms underlying γδ t-cell subset perturbations in siv-infected asian rhesus macaques.t cells that express the γδ t-cell receptor, which recognize microbial or stress-induced antigens, represent a minority of blood t cells but constitute a major proportion of intraepithelial lymphocytes in the gastrointestinal mucosa. as microbial products have been shown to translocate from the gastrointestinal tract into circulation in chronically hiv/simian immunodeficiency virus (siv)-infected individuals, we conducted a study of vδ1 and vδ2 t-cell frequency, phenotype, and function in blood, ...201020660793
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
simian immunodeficiency virus selectively infects proliferating cd4+ t cells in neonatal rhesus macaques.infants infected with hiv have a more severe course of disease and persistently higher viral loads than hiv-infected adults. however, the underlying pathogenesis of this exacerbation remains obscure. here we compared the rate of cd4(+) and cd8(+) t-cell proliferation in intestinal and systemic lymphoid tissues of neonatal and adult rhesus macaques, and of normal and age-matched simian immunodeficiency virus (siv)-infected neonates. the results demonstrate infant primates have much greater rates ...201020716768
cd8+ t cell recognition of cryptic epitopes is a ubiquitous feature of aids virus infection.vaccines designed to elicit aids virus-specific cd8+ t cells should engender broad responses. emerging data indicate that alternate reading frames (arfs) of both human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) encode cd8+ t cell epitopes, termed cryptic epitopes. here, we show that siv-specific cd8+ t cells from siv-infected rhesus macaques target 14 epitopes in eight arfs during siv infection. animals recognized up to five epitopes, totaling nearly one-quarter of the ...201020739530
damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections.the chronic phase of hiv infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or cd4(+) t cell count. recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically hiv-infected human ...201020808901
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
multiple sites in the n-terminal half of simian immunodeficiency virus capsid protein contribute to evasion from rhesus monkey trim5α-mediated restriction.we previously reported that cynomolgus monkey (cm) trim5α could restrict human immunodeficiency virus type 2 (hiv-2) strains carrying a proline at the 120th position of the capsid protein (ca), but it failed to restrict those with a glutamine or an alanine. in contrast, rhesus monkey (rh) trim5α could restrict all hiv-2 strains tested but not simian immunodeficiency virus isolated from macaque (sivmac), despite its genetic similarity to hiv-2.201020825647
interleukin-7 treatment counteracts ifn-α therapy-induced lymphopenia and stimulates siv-specific cytotoxic t lymphocyte responses in siv-infected rhesus macaques.interferon-α (ifn-α)-based therapy is presently the standard treatment for hepatitis c virus (hcv)-infected patients. despite good effectiveness, this cytokine is associated with major side effects, including significant lymphopenia, that limits its use for hiv/hcv-coinfected patients. interleukin-7 (il-7) has recently shown therapeutic potential and safety in several clinical trials designed to demonstrate t-cell restoration in immunodeficient patients. the purpose of this study was to evaluate ...201020841508
transgenic rhesus monkeys produced by gene transfer into early-cleavage-stage embryos using a simian immunodeficiency virus-based vector.the development of transgenic technologies in monkeys is important for creating valuable animal models of human physiology so that the etiology of diseases can be studied and potential therapies for their amelioration may be developed. however, the efficiency of producing transgenic primate animals is presently very low, and there are few reports of success. we have developed an improved methodology for the production of transgenic rhesus monkeys, making use of a simian immunodeficiency virus (s ...201020870965
cannabinoid administration attenuates the progression of simian immunodeficiency virus.abstract δ(9)-tetrahydrocannabinol (δ(9)-thc), the primary psychoactive component in marijuana, is fda approved to ameliorate aids-associated wasting. because cannabinoid receptors are expressed on cells of the immune system, chronic δ(9)-thc use may impact hiv disease progression. we examined the impact of chronic δ(9)-thc administration (0.32 mg/kg im, 2 × daily), starting 28 days prior to inoculation with simian immunodeficiency virus (siv(mac251); 100 tcid(50)/ml, iv), on immune and metaboli ...201020874519
a structural constraint for functional interaction between n-terminal and c-terminal domains in simian immunodeficiency virus capsid proteins.the gag capsid (ca) is one of the most conserved proteins in highly-diversified human and simian immunodeficiency viruses (hiv and siv). understanding the limitations imposed on amino acid sequences in ca could provide valuable information for vaccine immunogen design or anti-hiv drug development. here, by comparing two pathogenic siv strains, sivmac239 and sivsme543-3, we found critical amino acid residues for functional interaction between the n-terminal and the c-terminal domains in ca.201020955553
simian immunodeficiency virus from the sooty mangabey and rhesus macaque is modified with o-linked carbohydrate.although stretches of serine and threonine are sometimes sites for o-linked carbohydrate attachment, specific sequence and structural determinants for o-linked attachment remain ill defined. the gp120 envelope protein of sivmac239 contains a serine-threonine-rich stretch of amino acids at positions 128 to 139. here we show that lectin protein from jackfruit seed (jacalin), which binds to non- and monosialylated core 1 o-linked carbohydrate, potently inhibited the replication of sivmac239. select ...201020962077
macaque long-term nonprogressors resist superinfection with multiple cd8+ t cell escape variants of simian immunodeficiency virus.human immunodeficiency virus (hiv)-positive individuals can be superinfected with different virus strains. individuals who control an initial hiv infection are therefore still at risk for subsequent infection with divergent viruses, but the barriers to such superinfection remain unclear. here we tested long-term nonprogressors' (ltnps') susceptibility to superinfection using indian rhesus macaques that express the major histocompatibility complex class i (mhc-i) allele mamu-b 17, which is associ ...201020962091
enteric pathology and salmonella-induced cell death in healthy and siv-infected rhesus macaques.the goal of this study was to morphologically characterize a ligated ileal loop model of salmonella enterica serotype typhimurium infection in rhesus macaques (macaca mulatta) and to verify the occurrence of salmonella-induced cell death in vivo. eight adult healthy male rhesus macaques were used for ligated ileal loop surgery. four macaques had been intravenously inoculated with simian immunodeficiency virus (siv) mac251. ileal ligated loops were inoculated with wild-type (wt) s. typhimurium st ...201021041540
robust vaccine-elicited cellular immune responses in breast milk following systemic simian immunodeficiency virus dna prime and live virus vector boost vaccination of lactating rhesus monkeys.breast milk transmission of hiv remains an important mode of infant hiv acquisition. enhancement of mucosal hiv-specific immune responses in milk of hiv-infected mothers through vaccination may reduce milk virus load or protect against virus transmission in the infant gastrointestinal tract. however, the ability of hiv/siv strategies to induce virus-specific immune responses in milk has not been studied. in this study, five uninfected, hormone-induced lactating, mamu a*01(+) female rhesus monkey ...201021041730
broadening of cd8+ cell responses in vaccine-based simian immunodeficiency virus controllers.in our prior study on a prophylactic t-cell-based vaccine, some vaccinated macaques controlled a simian immunodeficiency virus (siv) challenge. these animals allowed viremia in the acute phase but showed persistent viral control after the setpoint. here, we examined the breadth of postchallenge virus-specific cellular immune responses in these siv controllers.201021045637
increased b7-h1 expression on dendritic cells correlates with programmed death 1 expression on t cells in simian immunodeficiency virus-infected macaques and may contribute to t cell dysfunction and disease progression.suppression of dendritic cell (dc) function in hiv-1 infection is thought to contribute to inhibition of immune responses and disease progression, but the mechanism of this suppression remains undetermined. using the rhesus macaque model, we show b7-h1 (programmed death [pd]-l1) is expressed on lymphoid and mucosal dcs (both myeloid dcs and plasmacytoid dcs), and its expression significantly increases after siv infection. meanwhile, its receptor, pd-1, is upregulated on t cells in both periphera ...201021059890
genomic analysis reveals pre- and postchallenge differences in a rhesus macaque aids vaccine trial: insights into mechanisms of vaccine efficacy.we have employed global transcriptional profiling of whole blood to identify biologically relevant changes in cellular gene expression in response to alternative aids vaccine strategies with subsequent viral challenge in a rhesus macaque vaccine model. samples were taken at day 0 (prechallenge), day 14 (peak viremia), and week 12 (set point) from animals immunized with replicating adenovirus type 5 host range (ad5hr) recombinant viruses expressing human immunodeficiency virus hiv(env)(89.6p), si ...201021068249
vaccine-induced t cells provide partial protection against high-dose rectal sivmac239 challenge of rhesus macaques.despite enormous efforts by the scientific community, an effective hiv vaccine remains elusive. to further address to what degree t cells in absence of antibodies may protect against simian immunodeficiency virus (siv) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived ad vector (adc) serotype 6 and then boosted intramuscularly with a serologically distinct adc vector of serotype 7 both expressing gag of sivmac239. animals were subsequently boosted int ...201021081905
myocarditis in cd8-depleted siv-infected rhesus macaques after short-term dual therapy with nucleoside and nucleotide reverse transcriptase inhibitors.although highly active antiretroviral therapy (haart) has dramatically reduced the morbidity and mortality associated with hiv infection, a number of antiretroviral toxicities have been described, including myocardial toxicity resulting from the use of nucleotide and nucleoside reverse transcriptase inhibitors (nrtis). current treatment guidelines recommend the use of haart regimens containing two nrtis for initial therapy of hiv-1 positive individuals; however, potential cardiotoxicity resultin ...201021203448
early myeloid dendritic cell dysregulation is predictive of disease progression in simian immunodeficiency virus infection.myeloid dendritic cells (mdc) are lost from blood in individuals with human immunodeficiency virus (hiv) infection but the mechanism for this loss and its relationship to disease progression are not known. we studied the mdc response in blood and lymph nodes of simian immunodeficiency virus (siv)-infected rhesus macaques with different disease outcomes. early changes in blood mdc number were inversely correlated with virus load and reflective of eventual disease outcome, as animals with stable i ...201021203477
loss of il-17-producing cd8 t cells during late chronic stage of pathogenic simian immunodeficiency virus infection.progressive disease caused by pathogenic siv/hiv infections is marked by systemic hyperimmune activation, immune dysregulation, and profound depletion of cd4(+) t cells in lymphoid and gastrointestinal mucosal tissues. il-17 is important for protective immunity against extracellular bacterial infections at mucosa and for maintenance of mucosal barrier. although il-17-secreting cd4 (th17) and cd8 (tc17) t cells have been reported, very little is known about the latter subset for any infectious di ...201021148794
blocking of α4β7 gut-homing integrin during acute infection leads to decreased plasma and gastrointestinal tissue viral loads in simian immunodeficiency virus-infected rhesus macaques.intravenous administration of a novel recombinant rhesus mab against the α4β7 gut-homing integrin (mab) into rhesus macaques just prior to and during acute siv infection resulted in significant decrease in plasma and gastrointestinal (gi) tissue viral load and a marked reduction in gi tissue proviral dna load as compared with control siv-infected rhesus macaques. this mab administration was associated with increases in peripheral blood naive and central memory cd4(+) t cells and maintenance of a ...201021149598
distinct host cell proteins incorporated by siv replicating in cd4+ t cells from natural disease resistant versus non-natural disease susceptible hosts.enveloped viruses including the simian immunodeficiency virus (siv) replicating within host cells acquire host proteins upon egress from the host cells. a number of studies have catalogued such host proteins, and a few have documented the potential positive and negative biological functions of such host proteins. the studies conducted herein utilized proteomic analysis to identify differences in the spectrum of host proteins acquired by a single source of siv replicating within cd4+ t cells from ...201021162735
persistence of gut mucosal innate immune defenses by enteric α-defensin expression in the simian immunodeficiency virus model of aids.gastrointestinal mucosa is an early target of hiv and a site of viral replication and severe cd4(+) t cell depletion. however, effects of hiv infection on gut mucosal innate immune defense have not been fully investigated. intestinal paneth cell-derived α-defensins constitute an integral part of the gut mucosal innate defense against microbial pathogens. using the siv-infected rhesus macaque model of aids, we examined the level of expression of rhesus enteric α-defensins (reds) in the jejunal mu ...201021178012
alcohol and hiv infection.alcohol abuse and human immunodeficiency virus (hiv) infection are major public health problems and frequently coexist in the same individual. although several studies have shown a significant association between alcohol consumption and the risk of being infected with hiv, it is unclear whether this association is due to behavioral and/or biomedical mechanisms. studies of hiv-infected patients are inherently limited in their ability to control for variables such as timing and dose of hiv exposur ...201021686230
partial protection against siv challenge by vaccination of adenovirus and mva vectors in rhesus monkeys.this study explores the effect of priming rhesus monkeys with an ad5/35 vector expressing simian immunodeficiency virus (siv) gag and gp120, and then boosting the animals with an modified vaccinia virus ankara (mva) vector encoding the same antigens after a 2-month interval. the animals were intravenously challenged with 100 tcid50 of highly pathogenic sivmac239 virus 2 months after the booster vaccination. the priming vaccination induced robust siv-specific cell-mediated and humoral immune resp ...201019759567
sex steroid hormones, hormonal contraception, and the immunobiology of human immunodeficiency virus-1 infection.worldwide, an increasing number of women use oral or injectable hormonal contraceptives. however, inadequate information is available to aid women and health care professionals in weighing the potential risks of hormonal contraceptive use in individuals living with hiv-1 or at high risk of infection. numerous epidemiological studies and challenge studies in a rhesus macaque model suggest that progesterone-based contraceptives increase the risk of hiv-1 infection in humans and simian immunodefici ...201019903932
envelope vaccination shapes viral envelope evolution following simian immunodeficiency virus infection in rhesus monkeys.the evolution of envelope mutations by replicating primate immunodeficiency viruses allows these viruses to escape from the immune pressure mediated by neutralizing antibodies. vaccine-induced anti-envelope antibody responses may accelerate and/or alter the specificity of the antibodies, thus shaping the evolution of envelope mutations in the replicating virus. to explore this possibility, we studied the neutralizing antibody response and the envelope sequences in rhesus monkeys vaccinated with ...201019906933
quantitative plasma proteomic profiling identifies the vitamin e binding protein afamin as a potential pathogenic factor in siv induced cns disease.investigating, predicting, diagnosing, and treating hiv-1-associated neurocognitive disorder (hand) has been hindered by the lack of disease-related molecular markers. in this study, plasma from rhesus monkeys (n = 6), before and after infection with simian immunodeficiency virus (siv), was profiled to obtain differential fingerprints in protein expression during siv-induced central nervous system (cns) disease. a quantitative proteomic analysis was performed by means of isobaric tag for relativ ...201019908921
nonpathogenesis of simian immunodeficiency virus infection is associated with reduced inflammation and recruitment of plasmacytoid dendritic cells to lymph nodes, not to lack of an interferon type i response, during the acute phase.divergent toll-like receptor 7 (tlr7) and tlr9 signaling has been proposed to distinguish pathogenic from nonpathogenic simian immunodeficiency virus infection in primate models. we demonstrate here that increased expression of type i interferon in pathogenic rhesus macaques compared to nonpathogenic african green monkeys was associated with the recruitment of plasmacytoid dendritic cells in the lymph nodes and the presence of an inflammatory environment early after infection, instead of a diffe ...201019939930
trafficking, persistence, and activation state of adoptively transferred allogeneic and autologous simian immunodeficiency virus-specific cd8(+) t cell clones during acute and chronic infection of rhesus macaques.despite multiple lines of evidence suggesting their involvement, the precise role of cd8(+) t cells in controlling hiv replication remains unclear. to determine whether cd8(+) t cells can limit retroviral replication in the absence of other immune responses, we transferred 1-13 x 10(9) allogeneic in vitro expanded siv-specific cd8(+) t cell clones matched for the relevant restricting mhc-i allele into rhesus macaques near the time of i.v. siv challenge. additionally, in vitro expanded autologous ...201019949089
distribution, persistence, and efficacy of adoptively transferred central and effector memory-derived autologous simian immunodeficiency virus-specific cd8+ t cell clones in rhesus macaques during acute infection.plasma viremia decreases coincident with the appearance of virus-specific cd8(+) t cells during acute hiv or siv infection. this finding, along with demonstrations of viral mutational escape from cd8(+) t cell responses and transient increase in plasma viremia after depletion of cd8(+) t cells in siv-infected monkeys strongly suggest a role for cd8(+) t cells in controlling hiv/siv. however, direct quantitative or qualitative correlates between cd8(+) t cell activity and virus control have not b ...201019949091
immunogenicity of viral vector, prime-boost siv vaccine regimens in infant rhesus macaques: attenuated vesicular stomatitis virus (vsv) and modified vaccinia ankara (mva) recombinant siv vaccines compared to live-attenuated siv.in a previously developed infant macaque model mimicking hiv infection by breast-feeding, we demonstrated that intramuscular immunization with recombinant poxvirus vaccines expressing simian immunodeficiency virus (siv) structural proteins provided partial protection against infection following oral inoculation with virulent siv. in an attempt to further increase systemic but also local antiviral immune responses at the site of viral entry, we tested the immunogenicity of different orally admini ...201019995539
preservation of memory cd4(+) t lymphocytes in breast milk of lactating rhesus monkeys during acute simian immunodeficiency virus infection.acute human immunodeficiency virus (hiv) or simian immunodeficiency virus (siv) infection is associated with a massive depletion of memory cd4(+) t lymphocytes in the gastrointestinal tract. to define the dynamics of the cd4(+) t lymphocyte subpopulations in breast milk during acute hiv or siv infection, lymphocyte populations were monitored in blood and milk of 4 mamu-a*01(+) rhesus monkeys after sivmac251 inoculation. strikingly, although the cd4(+) t lymphocytes in blood were depleted during ...201020001855
cytoskeletal proteins bound to heat-shock protein 70 may elicit resistance to simian immunodeficiency virus infection of cd4(+) t cells.this study is based on the evidence that immunization of macaques with human cd4(+) t cells elicits prevention of simian immunodeficiency virus (siv) infection. we hypothesized that heat-shock protein 70 (hsp70) isolated from cd4(+) t cells may act as a chaperone and carry the protective host proteins. two moieties of hsp70 were affinity-purified from human cd4(+) t cells; an adp preparation with hsp70-bound proteins (adp-hsp) and an atp control preparation. immunization of rhesus macaques with ...201020002211
small intestine cd4+ cell reduction and enteropathy in simian/human immunodeficiency virus ks661-infected rhesus macaques in the presence of low viral load.human immunodeficiency virus type 1, simian immunodeficiency virus and simian/human immunodeficiency virus (shiv) infection generally lead to death of the host accompanied by high viraemia and profound cd4(+) t-cell depletion. shiv clone ks661-infected rhesus macaques with a high viral load set point (hvl) ultimately experience diarrhoea and wasting at 6-12 months after infection. in contrast, infected macaques with a low viral load set point (lvl) usually live asymptomatically throughout the ob ...201019889928
durable mucosal simian immunodeficiency virus-specific effector memory t lymphocyte responses elicited by recombinant adenovirus vectors in rhesus monkeys.the induction of potent and durable cellular immune responses in both peripheral and mucosal tissues may be important for the development of effective vaccines against human immunodeficiency virus type 1 and other pathogens. in particular, effector responses at mucosal surfaces may be critical to respond rapidly to incoming mucosal pathogens. here we report that intramuscular injection of nonreplicating recombinant adenovirus (rad) vectors into rhesus monkeys induced remarkably durable simian im ...201121917969
The simian immunodeficiency virus targets central cell cycle functions through transcriptional repression in vivo.A massive and selective loss of CD4+ memory T cells occurs during the acute phase of immunodeficiency virus infections. The mechanism of this depletion is poorly understood but constitutes a key event with implications for progression. We assessed gene expression of purified T cells in Rhesus Macaques during acute SIVmac239 infection in order to define mechanisms of pathogenesis. We observe a general transcriptional program of over 1,600 interferon-stimulated genes induced in all T cells by the ...201122043290
evidence for an increased risk of transmission of simian immunodeficiency virus and malaria in a rhesus macaque coinfection model.in sub-saharan africa, hiv-1 infection frequently occurs in the context of other coinfecting pathogens, most importantly, mycobacterium tuberculosis and malaria parasites. the consequences are often devastating, resulting in enhanced morbidity and mortality. due to the large number of confounding factors influencing pathogenesis in coinfected people, we sought to develop a nonhuman primate model of simian immunodeficiency virus (siv)-malaria coinfection. in sub-saharan africa, plasmodium falcipa ...201121917966
correlation between cd4+ t-cell loss and gag-specific t cells in different intestinal sites of chronically siv-infected rhesus monkeys.to determine the loss of cd4+ t cells and virus-specific cytotoxic t cells (ctl) in different mucosal sites of rhesus monkeys infected with simian immunodeficiency virus (siv).201121192228
simian immunodeficiency virus sivmac239deltanef vaccination elicits different tat28-35sl8-specific cd8+ t-cell clonotypes compared to a dna prime/adenovirus type 5 boost regimen in rhesus macaques.different human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) vaccine vectors expressing the same viral antigens can elicit disparate t-cell responses. within this spectrum, replicating variable vaccines, like sivmac239?nef, appear to generate particularly efficacious cd8(+) t-cell responses. here, we sequenced t-cell receptor ß-chain (trb) gene rearrangements from immunodominant mamu-a 01-restricted tat(28-35)sl8-specific cd8(+) t-cell populations together with the correspond ...201121270159
functional analysis of frequently expressed chinese rhesus macaque mhc class i molecules mamu-a1*02601 and mamu-b*08301 reveals hla-a2 and hla-a3 supertypic specificities.the simian immunodeficiency virus (siv)-infected indian rhesus macaque (macaca mulatta) is the most established model of hiv infection and aids-related research, despite the potential that macaques of chinese origin is a more relevant model. ongoing efforts to further characterize the chinese rhesus macaques' major histocompatibility complex (mhc) for composition and function should facilitate greater utilization of the species. previous studies have demonstrated that chinese-origin m. mulatta ( ...201121274527
double-positive cd21+cd27+ b cells are highly proliferating memory cells and their distribution differs in mucosal and peripheral tissues.several b-cell defects arise in hiv infected patients, particularly in patients with chronic infection and high viral load. loss of memory b cells (cd27(+) b cells) in peripheral blood and lymphoid tissues is one of the major b cell dysfunctions in hiv and simian immunodeficiency virus (siv) infection. despite several studies, definitive identification of memory b cells based on cd27 surface expression has not been described. similarly, the rates of cell turnover in different b cell subpopulatio ...201121304587
epitope-specific cd8+ t lymphocytes cross-recognize mutant simian immunodeficiency virus (siv) sequences but fail to contain very early evolution and eventual fixation of epitope escape mutations during siv infection.human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) evade containment by cd8(+) t lymphocytes through focused epitope mutations. however, because of limitations in the numbers of viral sequences that can be sampled, traditional sequencing technologies have not provided a true representation of the plasticity of these viruses or the intensity of cd8(+) t lymphocyte-mediated selection pressure. moreover, the strategy by which cd8(+) t lymphocytes contain evolving viral quasi ...201121307185
cryptosporidiosis in rhesus macaques challenged during acute and chronic phases of siv infection.abstract the intestinal immune dysfunction due to loss of mucosal and peripheral cd4(+) t cells in individuals with hiv/aids is presumably responsible for the establishment of persistent cryptosporidiosis. simian immunodeficiency virus (siv)-infected macaques were used to investigate the phase/timing in siv infection, which permits a self-limiting cryptosporidium parvum infection to become persistent in immunodeficient hosts because of significant mucosal immune defects. two groups of siv-infect ...201121314434
long-term control of simian immunodeficiency virus mac251 viremia to undetectable levels in half of infected female rhesus macaques nasally vaccinated with simian immunodeficiency virus dna/recombinant modified vaccinia virus ankara.the efficacy of two siv dna plus recombinant modified vaccinia virus ankara nasal vaccine regimens, one combined with plasmids expressing il-2 and il-15, the other with plasmids expressing gm-csf, il-12, and tnf-a, which may better stimulate humoral responses, was evaluated in two female rhesus macaque groups. vaccination stimulated significant siv-specific mucosal and systemic cell-mediated immunity in both groups, whereas siv-specific iga titers were sporadic and igg titers negative. all vacci ...201121317390
characterization and allelic polymorphisms of rhesus macaque (macaca mulatta) igg fc receptor genes.macaque models are invaluable for aids research. indeed, initial development of hiv-1 vaccines relies heavily on simian immunodeficiency virus-infected rhesus macaques. neutralizing antibodies, a major component of anti-hiv protective responses, ultimately interact with fc receptors on phagocytic and natural killer cells to eliminate the pathogen. despite the major role that fc receptors play in protective responses, there is very limited information available on these molecules in rhesus macaqu ...201121327607
topical nonnucleoside reverse transcriptase inhibitor mc 1220 partially prevents vaginal rt-shiv infection of macaques.abstract the availability of an effective vaginal microbicide would be a major step toward containment of hiv transmission as well as allowing women self-protection against hiv infection. here we evaluated the efficacy of vaginal application of the potent nonnucleoside reverse transcriptase inhibitor (nnrti) mc 1220 against vaginal challenge of macaques with rt-shiv, a chimeric simian immunodeficiency virus (siv) containing the reverse transcriptase (rt) gene of hiv-1. challenge infection of mon ...201121332419
major histocompatibility complex class i-restricted cytotoxic t lymphocyte responses during primary simian immunodeficiency virus infection in burmese rhesus macaques.major histocompatibility complex class i (mhc-i)-restricted cd8(+) cytotoxic t lymphocyte (ctl) responses are crucial for the control of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) replication. in particular, gag-specific ctl responses have been shown to exert strong suppressive pressure on hiv/siv replication. additionally, association of vif-specific ctl frequencies with in vitro anti-siv efficacy has been suggested recently. host mhc-i genotypes could affect th ...201121895748
distinct expression patterns of cd69 in mucosal and systemic lymphoid tissues in primary siv infection of rhesus macaques.although the intestinal tract plays a major role in early human immunodeficiency virus (hiv) infection, the role of immune activation and viral replication in intestinal tissues is not completely understood. further, increasing evidence suggests the early leukocyte activation antigen cd69 may be involved in the development or regulation of important t cell subsets, as well as a major regulatory molecule of immune responses. using the simian immunodeficiency virus (siv) rhesus macaque model, we c ...201122096538
association of activating kir copy number variation of nk cells with containment of siv replication in rhesus monkeys.while the contribution of cd8(+) cytotoxic t lymphocytes to early containment of hiv-1 spread is well established, a role for nk cells in controlling hiv-1 replication during primary infection has been uncertain. the highly polymorphic family of kir molecules expressed on nk cells can inhibit or activate these effector cells and might therefore modulate their activity against hiv-1-infected cells. in the present study, we investigated copy number variation in kir3dh loci encoding the only activa ...201122194686
TRIM5 allelic polymorphism in macaque species/populations of different geographic origins: its impact on SIV vaccine studies.Tripartite motif 5a (TRIM5a) is a potent antiretroviral immune factor present in the cytoplasm of cells of most tissue types. The rhesus macaque TRIM5 gene has been shown to display polymorphism, with different variants being divided into three groups (TRIM5(TFP), TRIM5(Q), and TRIM5(CypA)), which may have divergent retroviral effects on infection. Along with rhesus macaques, cynomolgus macaques are also used in simian immunodeficiency virus (SIV) infection studies. As a consequence, TRIM5 genot ...201121929574
association of tlr7 variants with aids-like disease and aids vaccine efficacy in rhesus macaques.in hiv infection, tlr7-triggered ifn-α production exerts a direct antiviral effect through the inhibition of viral replication, but may also be involved in immune pathogenesis leading to aids. tlr7 could also be an important mediator of vaccine efficacy. in this study, we analyzed polymorphisms in the x-linked tlr7 gene in the rhesus macaque model of aids. upon resequencing of the tlr7 gene in 36 rhesus macaques of indian origin, 12 polymorphic sites were detected. next, we identified three tigh ...201122022401
myeloid dendritic cells isolated from tissues of siv-infected rhesus macaques promote the induction of regulatory t-cells.objective:: to determine whether the ability of primary myeloid dendritic cells (mdc) to induce regulatory t cells (treg) is affected by chronic siv infection. design:: modulation of dc activity with the aim of influencing treg frequency may lead to new treatment options for hiv and strategies for vaccine development. methods:: eleven chronically-infected siv rhesus macaques were compared with four uninfected animals. immature and mature mdc were isolated from mesenteric lymph nodes and spleen b ...201122095196
targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus dna.the majority of hiv infections occur via mucosal transmission. vaccines that induce memory t and b cells in the female genital tract may prevent the establishment and systemic dissemination of hiv. we tested the immunogenicity of a vaccine that uses human papillomavirus (hpv)-based gene transfer vectors, also called pseudovirions (psvs), to deliver siv genes to the vaginal epithelium. our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomol ...201122174446
Interleukin-21 administration to rhesus macaques chronically infected with simian immunodeficiency virus increases cytotoxic effector molecules in T cells and NK cells and enhances B cell function without increasing immune activation or viral replication.We have previously shown that interleukin-21, a pleiotropic C ?-chain signaling cytokine, induces the expression of the cytotoxic molecules granzyme B (GrB) and perforin in vitro in CD8 T cells and NK cells of chronically HIV infected individuals. In this pilot study, four chronically SIV infected rhesus macaques (RM) in late-stage disease were given two doses of recombinant MamuIL-21, 50 µg/kg, intravenously 7 days apart, followed by one subcutaneous dose, 100 µg/kg, 23 days after the second do ...201121996099
SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses.BACKGROUND: Vaccine regimens using different agents for priming and boosting have become popular for enhancing T cell and Ab responses elicited by candidate HIV/AIDS vaccines. Here we use a simian model to evaluate immunogenicity and protective efficacy of a recombinant modified vaccinia Ankara (MVA) vaccine in the presence and absence of a recombinant DNA prime. The simian vaccines and regimens represent prototypes for candidate HIV vaccines currently undergoing clinical testing. METHOD: Recomb ...201122178526
geographic, genetic and functional diversity of antiretroviral host factor trimcyp in cynomolgus macaque (macaca fascicularis).the antiretroviral factor trim5 gene-derived isoform, trimcyp, was found in at least three species of old world monkey, rhesus (macaca mulatta), pig-tailed (macaca nemestrina), and cynomolgus macaques (macaca fascicularis). although the frequency of trimcyp has been well studied in rhesus and pig-tailed macaques, the frequency and prevalence of trimcyp in the cynomolgus macaque remain to be definitively elucidated. here, we studied the geographic and genetic diversity of trim5α/trimcyp in cynomo ...201122113010
Structural basis of diverse Peptide accommodation by the rhesus macaque MHC class I molecule mamu-b*17: insights into immune protection from simian immunodeficiency virus.The MHC class I molecule Mamu-B*17 has been associated with elite control of SIV infection in rhesus macaques, akin to the protective effects described for HLA-B*57 in HIV-infected individuals. In this study, we determined the crystal structures of Mamu-B*17 in complex with eight different peptides corresponding to immunodominant SIV(mac)239-derived CD8(+) T cell epitopes: HW8 (HLEVQGYW), GW10 (GSHLEVQGYW), MW9 (MHPAQTSQW), QW9 (QTSQWDDPW), FW9 (FQWMGYELW), MF8 (MRHVLEPF), IW9 (IRYPKTFGW), and I ...201122084443
increased apobec3g and apobec3f expression is associated with low viral load and prolonged survival in simian immunodeficiency virus infected rhesus monkeys.the cytidine deaminases apobec3g (a3g) and apobec3f (a3f) are innate cellular factors that inhibit replication of a number of viruses, including hiv-1. since antiviral activity of apobec3 has been mainly confirmed by in vitro data, we examined their role for disease progression in the siv/macaque model for aids.201121955401
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