Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virus-specific ctl.we previously demonstrated that hiv replication is concentrated in lymph node b cell follicles during chronic infection and that hiv-specific ctl fail to accumulate in large numbers at those sites. it is unknown whether these observations can be generalized to other secondary lymphoid tissues or whether virus compartmentalization occurs in the absence of ctl. we evaluated these questions in sivmac239-infected rhesus macaques by quantifying siv rna(+) cells and siv-specific ctl in situ in spleen, ...201425362178
expansion of dysfunctional tim-3-expressing effector memory cd8+ t cells during simian immunodeficiency virus infection in rhesus macaques.the t cell ig- and mucin domain-containing molecule-3 (tim-3) negative immune checkpoint receptor demarcates functionally exhausted cd8(+) t cells arising from chronic stimulation in viral infections like hiv. tim-3 blockade leads to improved antiviral cd8(+) t cell responses in vitro and, therefore, represents a novel intervention strategy to restore t cell function in vivo and protect from disease progression. however, the tim-3 pathway in the physiologically relevant rhesus macaque siv model ...201425348621
novel vaccine vectors for hiv-1.the ultimate solution to the global hiv-1 epidemic will probably require the development of a safe and effective vaccine. multiple vaccine platforms have been evaluated in preclinical and clinical trials, but given the disappointing results of clinical efficacy studies so far, novel vaccine approaches are needed. in this opinion article, we discuss the scientific basis and clinical potential of novel adenovirus and cytomegalovirus vaccine vectors for hiv-1 as two contrasting but potentially comp ...201425296195
transcriptional profiling of peripheral cd8+t cell responses to sivδnef and sivmac251 challenge reveals a link between protective immunity and induction of systemic immunoregulatory mechanisms.immunization of macaques with attenuated simian immunodeficiency virus (siv) with deletions in nef (sivδnef) is shown to elicit protective immunity to infection by pathogenic siv, yet the mechanisms that orchestrate protection and prevent pathogenesis remains unknown. we utilized whole-genome transcriptional profiling to reveal molecular signatures of protective immunity in circulating cd8+ t cells of rhesus macaques vaccinated with sivmac239δnef and challenged with pathogenic sivmac251. our fin ...201425282469
growth properties of macaque-tropic hiv-1 clones carrying vpr/vpx genes derived from simian immunodeficiency viruses in place of their vpr regions.we have previously generated a macaque-tropic human immunodeficiency virus type 1 (hiv-1mt) clone designated mn4/lsdqgtu by genetic manipulation from a parental virus that replicates poorly in rhesus macaque cells. in rhesus cell line m1.3s and peripheral blood mononuclear cells (pbmcs), mn4/lsdqgtu grows comparably to a standard simian immunodeficiency virus clone derived from the rhesus macaque (sivmac239) that can induce the acquired immunodeficiency syndrome (aids) in the animals. in this st ...201425264057
chronic binge alcohol consumption does not diminish effectiveness of continuous antiretroviral suppression of viral load in simian immunodeficiency virus-infected macaques.alcohol use disorders (auds) are a frequent comorbidity in a large percentage of people living with hiv/aids (plwha). plwha with comorbid auds are consistently found to perform poorly at most levels of the hiv treatment cascade, resulting in a higher likelihood of virologic nonsuppression. this has been partly attributed to lower rates of persistence with and adherence to antiretroviral therapies (art). focus groups of in-care plwha identify the need to suspend art on drinking days because of th ...201425257285
accumulation of functionally immature myeloid dendritic cells in lymph nodes of rhesus macaques with acute pathogenic simian immunodeficiency virus infection.myeloid dendritic cells (mdc) are key mediators of innate and adaptive immunity to virus infection, but the impact of hiv infection on the mdc response, particularly early in acute infection, is ill-defined. we studied acute pathogenic simian immunodeficiency virus (siv) infection of rhesus macaques to address this question. the mdc in blood and bone marrow were depleted within 12 days of intravenous infection with sivmac251, associated with a marked proliferative response. in lymph nodes, mdc w ...201424684292
vaccination against endogenous retrotransposable element consensus sequences does not protect rhesus macaques from sivsme660 infection and replication.the enormous sequence diversity of hiv remains a major roadblock to the development of a prophylactic vaccine and new approaches to induce protective immunity are needed. endogenous retrotransposable elements (ere) such as endogenous retrovirus k (erv)-k and long interspersed nuclear element-1 (line-1) are activated during hiv-1-infection and could represent stable, surrogate targets to eliminate hiv-1-infected cells. here, we explored the hypothesis that vaccination against ere would protect ma ...201424651676
modified interferon-α subtypes production and chemokine networks in the thymus during acute simian immunodeficiency virus infection, impact on thymopoiesis.thymus dysfunction characterizes human/simian immunodeficiency virus (siv) infections and contributes to physiopathology. however, both the mechanisms involved in thymic dysfunction and its precise timing remain unknown. we here analyzed thymic function during acute siv infection in rhesus macaques.201424614087
exposure to miv-150 from a high-dose intravaginal ring results in limited emergence of drug resistance mutations in shiv-rt infected rhesus macaques.when microbicides used for hiv prevention contain antiretroviral drugs, there is concern for the potential emergence of drug-resistant hiv following use in infected individuals who are either unaware of their hiv infection status or who are aware but still choose to use the microbicide. resistant virus could ultimately impact their responsiveness to treatment and/or result in subsequent transmission of drug-resistant virus. we tested whether drug resistance mutations (drms) would emerge in macaq ...201424586674
comparison of the vaginal environment of macaca mulatta and macaca nemestrina throughout the menstrual cycle.pigtail macaques, macaca nemestrina (pt), are more susceptible to vaginal transmission of simian immunodeficiency virus (siv) and other sexually transmitted diseases (std) than rhesus macaques (rm). however, comparative studies to explore the reasons for these differences are lacking.201424521395
increased stability and limited proliferation of cd4+ central memory t cells differentiate nonprogressive simian immunodeficiency virus (siv) infection of sooty mangabeys from progressive siv infection of rhesus macaques.depletion of cd4(+) central memory t (tcm) cells dictates the tempo of progression to aids in simian immunodeficiency virus (siv)-infected rhesus macaques (rms) both in the natural history of infection and in the context of vaccination. cd4(+) tcm cells of sooty mangabeys (sms), a natural host for siv in which infection is nonpathogenic, are less susceptible to siv infection than cd4(+) tcm cells of rms. whether this relative protection from infection translates into increased stability of cd4(+ ...201424501416
variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of rt-shiv.rt-shiv is a chimera of simian immunodeficiency virus (siv) containing the reverse transcriptase (rt)-encoding region of human immunodeficiency virus type 1 (hiv-1) within the backbone of sivmac239. it has been used in a non-human primate model for studies of non-nucleoside rt inhibitors (nnrti) and highly active antiretroviral therapy (haart). we and others have identified several mutations that arise in the "foreign" hiv-1 rt of rt-shiv during in vivo replication. in this study we catalogued a ...201424498008
giant cell encephalitis and microglial infection with mucosally transmitted simian-human immunodeficiency virus shivsf162p3n in rhesus macaques.neurocognitive disorders such as dementia and cognitive/motor impairments are among the most significant complications associated with human immunodeficiency virus (hiv) infection, especially in aging populations, yet the pathogenesis remains poorly understood. activated macrophages and microglia in white matter along with the hallmark multinucleated giant cells are prominent features of hiv encephalitis (hive) and of several simian immunodeficiency virus (siv) models. while infected microglia h ...201424464410
analysis of the n-terminal positively charged residues of the simian immunodeficiency virus vif reveals a critical amino acid required for the antagonism of rhesus apobec3d, g, and h.previous studies have shown that apolipoprotein b mrna editing, enzyme catalytic, polypeptide g (apobec3g; ha3g) and f (apobec3f; ha3f) proteins interact with a nonlinear binding site located at the n-terminal region of the hiv-1 vif protein. we have analyzed the role of 12 positively charged amino acids of the n-terminal region of the siv vif. simian-human immunodeficiency viruses (shiv) were constructed that expressed each of these amino acid substitutions. these viruses were examined for repl ...201424418547
modulation of gut-specific mechanisms by chronic δ(9)-tetrahydrocannabinol administration in male rhesus macaques infected with simian immunodeficiency virus: a systems biology analysis.our studies have demonstrated that chronic δ(9)-tetrahydrocannabinol (thc) administration results in a generalized attenuation of viral load and tissue inflammation in simian immunodeficiency virus (siv)-infected male rhesus macaques. gut-associated lymphoid tissue is an important site for hiv replication and inflammation that can impact disease progression. we used a systems approach to examine the duodenal immune environment in 4- to 6-year-old male rhesus monkeys inoculated intravenously with ...201424400995
bovine alpha-2-hs-glycoprotein functions as a booster antigen for efficiently stimulating humoral immune responses to ccr5 and sivmac239 envelope glycoprotein.the presence of anti-ccr5 and anti-hiv-1 envelope glycoprotein (env) gp41 antibodies (abs) at sites of hiv-1 exposure was effective in preventing its transmission to hiv-1-exposed seronegative (esn) subjects. here, we design an immunogen that can induce abs against ccr5 and sivmac239 env simultaneously and show that bovine alpha-2-hs-glycoprotein (bahsg) functions as a booster antigen for efficiently stimulating humoral immune responses to ccr5 and env. initially, we generated a rhesus ccr5-deri ...201424309114
form follows function: astrocyte morphology and immune dysfunction in siv neuroaids.cortical function is disrupted in neuroinflammatory disorders, including hiv-associated neurocognitive disorders (hand). astrocyte dysfunction includes retraction of foot processes from the blood-brain barrier and decreased removal of neurotransmitters from synaptic clefts. mechanisms of astrocyte activation, including innate immune function and the fine neuroanatomy of astrocytes, however, remain to be investigated. we quantified the number of glial fibrillary acidic protein (gfap)-labeled astr ...201424970236
cytokine/chemokine responses in activated cd4+ and cd8+ t cells isolated from peripheral blood, bone marrow, and axillary lymph nodes during acute simian immunodeficiency virus infection.understanding the cytokine/chemokine networks in cd4(+) and cd8(+) t cells during the acute phase of infection is crucial to design therapies for the control of early human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) replication. here, we measured early changes in cd4(+) and cd8(+) t cells in the peripheral blood (pb), bone marrow (bm), and axillary lymph node (aln) tissue of rhesus macaques infected with sivmac251. at 21 days after infection, all tissues showed a statistica ...201424920807
cd40l-adjuvanted dna/modified vaccinia virus ankara simian immunodeficiency virus siv239 vaccine enhances siv-specific humoral and cellular immunity and improves protection against a heterologous sive660 mucosal challenge.it remains a challenge to develop a successful human immunodeficiency virus (hiv) vaccine that is capable of preventing infection. here, we utilized the benefits of cd40l, a costimulatory molecule that can stimulate both dendritic cells (dcs) and b cells, as an adjuvant for our simian immunodeficiency virus (siv) dna vaccine in rhesus macaques. we coexpressed the cd40l with our dna/siv vaccine such that the cd40l is anchored on the membrane of siv virus-like particle (vlp). these cd40l containin ...201424920805
lipopolysaccharide induces immune activation and siv replication in rhesus macaques of chinese origin.chronic immune activation is a hallmark of progressive hiv infection and a key determinant of immunodeficiency in hiv-infected individuals. bacterial lipopolysaccharide (lps) in the circulation has been implicated as a key factor in hiv infection-related systemic immune activation. we thus investigate the impact of lps on systemic immune activation in simian immunodeficiency virus (siv)-infected rhesus macaques of chinese origin.201424918575
humoral immunity induced by mucosal and/or systemic siv-specific vaccine platforms suggests novel combinatorial approaches for enhancing responses.combinatorial hiv/siv vaccine approaches targeting multiple arms of the immune system might improve protective efficacy. we compared siv-specific humoral immunity induced in rhesus macaques by five vaccine regimens. systemic regimens included alvac-sivenv priming and env boosting (alvac/env); dna immunization; and dna plus env co-immunization (dna&env). repad/env combined mucosal replication-competent ad-env priming with systemic env boosting. a peptide/env regimen, given solely intrarectally, i ...201424907411
the effects of chronic binge alcohol on the genital microenvironment of simian immunodeficiency virus-infected female rhesus macaques.alcohol abuse is a widespread problem among those at risk for and living with hiv and can impact transmission and disease progression. in this study we sought to use the simian immunodeficiency virus (siv)-macaque model to evaluate the immunological and virological changes in the genital microenvironment of females exposed to chronic alcohol. female rhesus macaques were treated with alcohol (n=6) or isocaloric sucrose (n=6) for 3 months and then inoculated with sivmac251. to assess the effects o ...201424902876
nk cell responses to simian immunodeficiency virus vaginal exposure in naive and vaccinated rhesus macaques.nk cell responses to hiv/siv infection have been well studied in acute and chronic infected patients/monkeys, but little is known about nk cells during viral transmission, particularly in mucosal tissues. in this article, we report a systematic study of nk cell responses to high-dose vaginal exposure to sivmac251 in the rhesus macaque female reproductive tract (frt). small numbers of nk cells were recruited into the frt mucosa following vaginal inoculation. the influx of mucosal nk cells precede ...201424899503
resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive trim5α expression in pbmc.at least six host-encoded restriction factors (rfs), apobec3g, trim5α, tetherin, samhd1, schlafen 11, and mx2 have now been shown to inhibit hiv and/or siv replication in vitro. to determine their role in vivo in the resistance of macaques to mucosally-acquired siv, we quantified both pre-exposure (basal) and post-exposure mrna levels of these rfs, mx1, and ifnγ in pbmc, lymph nodes, and duodenum of rhesus macaques undergoing weekly low dose rectal exposures to the primary isolate, siv/deltab670 ...201424884551
molecularly tagged simian immunodeficiency virus sivmac239 synthetic swarm for tracking independent infection events.following mucosal human immunodeficiency virus type 1 transmission, systemic infection is established by one or only a few viral variants. modeling single-variant, mucosal transmission in nonhuman primates using limiting-dose inoculations with a diverse simian immunodeficiency virus isolate stock may increase variability between animals since individual variants within the stock may have substantial functional differences. to decrease variability between animals while retaining the ability to en ...201424807714
deep transcriptional sequencing of mucosal challenge compartment from rhesus macaques acutely infected with simian immunodeficiency virus implicates loss of cell adhesion preceding immune activation.pathology resulting from human immunodeficiency virus (hiv) infection is driven by protracted inflammation; the primary loss of cd4(+) t cells is caused by activation-driven apoptosis. recent studies of nonhuman primates (nhps) have suggested that during the acute phase of infection, antiviral mucosal immunity restricts viral replication in the primary infection compartment. these studies imply that hiv achieves systemic infection as a consequence of a failure in host antiviral immunity. here, w ...201424807713
enhanced antiretroviral therapy in rhesus macaques improves rt-shiv viral decay kinetics.using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (siv) consisting of sivmac239 with the human immunodeficiency virus type 1 (hiv-1) reverse transcriptase from clone hxbc2 (rt-shiv). the impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (haart) on early viral decay and rebound were determined. the four-drug combination consisted of an integrase inhibitor, l-870-812 (l-812), tog ...201424777106
tcr affinity associated with functional differences between dominant and subdominant siv epitope-specific cd8+ t cells in mamu-a*01+ rhesus monkeys.many of the factors that contribute to cd8+ t cell immunodominance hierarchies during viral infection are known. however, the functional differences that exist between dominant and subdominant epitope-specific cd8+ t cells remain poorly understood. in this study, we characterized the phenotypic and functional differences between dominant and subdominant simian immunodeficiency virus (siv) epitope-specific cd8+ t cells restricted by the major histocompatibility complex (mhc) class i allele mamu-a ...201424743648
tlr3-responsive, xcr1+, cd141(bdca-3)+/cd8α+-equivalent dendritic cells uncovered in healthy and simian immunodeficiency virus-infected rhesus macaques.in mice, cd8α(+) myeloid dendritic cells (mdc) optimally cross-present ags to cd8(+) t cells and respond strongly to tlr3 ligands. although equivalent dc have been identified by comparative genomic analysis and functional studies in humans as xcr1(+)cd141 (bdca-3)(+)clec9a(+)cell adhesion molecule 1(+) mdc, and in sheep as cd26(+) mdc, these cells remained elusive in nonhuman primates. to remedy this situation, we delineated precisely dc and monocyte populations by 12-color flow cytometry and tr ...201424740505
a simian-human immunodeficiency virus carrying the rt gene from chinese crf01_ae strain of hiv is sensitive to nucleoside reverse transcriptase inhibitors and has a highly genetic stability in vivo.human immunodeficiency virus (hiv)-1 subtype crf01_ae is one of the major hiv-1 subtypes that dominate the global epidemic. however, its drug resistance, associated mutations, and viral fitness have not been systemically studied, because available chimeric simian-hivs (shivs) usually express the hiv-1 reverse transcriptase (rt) gene of subtype b hiv-1, which is different from subtype crf01_ae hiv-1. in this study, a recombinant plasmid, prt-shiv/ae, was constructed to generate a chimeric rt-shiv ...201424709063
characterization of simian immunodeficiency virus (siv) that induces siv encephalitis in rhesus macaques with high frequency: role of trim5 and major histocompatibility complex genotypes and early entry to the brain.although nonhuman primate models of neuro-aids have made tremendous contributions to our understanding of disease progression in the central nervous system (cns) of human immunodeficiency virus type 1 (hiv-1)-infected individuals, each model holds advantages and limitations. in this study, in vivo passage of sivsme543 was conducted to obtain a viral isolate that can induce neuropathology in rhesus macaques. after a series of four in vivo passages in rhesus macaques, we have successfully isolated ...201425187546
effect of suberoylanilide hydroxamic acid (saha) administration on the residual virus pool in a model of combination antiretroviral therapy-mediated suppression in sivmac239-infected indian rhesus macaques.nonhuman primate models are needed for evaluations of proposed strategies targeting residual virus that persists in hiv-1-infected individuals receiving suppressive combination antiretroviral therapy (cart). however, relevant nonhuman primate (nhp) models of cart-mediated suppression have proven challenging to develop. we used a novel three-class, six-drug cart regimen to achieve durable 4.0- to 5.5-log reductions in plasma viremia levels and declines in cell-associated viral rna and dna in bloo ...201425182644
lack of interleukin-10-mediated anti-inflammatory signals and upregulated interferon gamma production are linked to increased intestinal epithelial cell apoptosis in pathogenic simian immunodeficiency virus infection.interleukin-10 (il-10) is an immunomodulatory cytokine that is important for maintenance of epithelial cell (ec) survival and anti-inflammatory responses (air). the majority of hiv infections occur through the mucosal route despite mucosal epithelium acting as a barrier to human immunodeficiency virus (hiv). therefore, understanding the role of il-10 in maintenance of intestinal homeostasis during hiv infection is of interest for better characterization of the pathogenesis of hiv-mediated entero ...201425165117
live simian immunodeficiency virus vaccine correlate of protection: immune complex-inhibitory fc receptor interactions that reduce target cell availability.principles to guide design of an effective vaccine against hiv are greatly needed, particularly to protect women in the pandemic's epicenter in africa. we have been seeking these principles by identifying correlates of the robust protection associated with sivmac239δnef vaccination in the siv-rhesus macaque animal model of hiv-1 transmission to women. we identified one correlate of sivmac239δnef protection against vaginal challenge as a resident mucosal system for siv-gp41 trimer ab production a ...201425143442
live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry.we sought design principles for a vaccine to prevent hiv transmission to women by identifying correlates of protection conferred by a highly effective live attenuated siv vaccine in the rhesus macaque animal model. we show that sivmac239δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. the plasma cells and ectopic follicles produce igg abs reactive with viral envelope glycoprotein ...201425135832
chronic δ⁹-tetrahydrocannabinol administration may not attenuate simian immunodeficiency virus disease progression in female rhesus macaques.persons living with hiv/aids (plwha) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9-tetrahydrocannabinol; δ(9)-thc dronabinol). previously, we demonstrated that chronic δ(9)-thc administration decreases early mortality in male simian immunodeficiency virus (siv)-infected macaques. in this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in siv-infected female rhesus macaques. clini ...201425113915
reduction of pyramidal and immature hippocampal neurons in pediatric simian immunodeficiency virus infection.pediatric hiv infection remains a global health crisis with a worldwide infection rate of 2.5 million (who, geneva switzerland, 2009). children are much more susceptible to hiv-1 neurological impairments compared with adults, which is exacerbated by coinfections. a major obstacle in pediatric hiv research is sample access. the proposed studies take advantage of ongoing pediatric simian immunodeficiency virus (siv) pathogenesis and vaccine studies to test the hypothesis that pediatric siv infecti ...201425102373
atypical nodular astrocytosis in simian immunodeficiency virus-infected rhesus macaques (macaca mulatta).simian immunodeficiency virus (siv), a model for hiv pathogenesis, is associated with neuropathology.201425082291
recombinant mycobacterium bovis bacillus calmette-guérin vectors prime for strong cellular responses to simian immunodeficiency virus gag in rhesus macaques.live attenuated nonpathogenic mycobacterium bovis bacillus calmette-guérin (bcg) mediates long-lasting immune responses, has been safely administered as a tuberculosis vaccine to billions of humans, and is affordable to produce as a vaccine vector. these characteristics make it very attractive as a human immunodeficiency virus (hiv) vaccine vector candidate. here, we assessed the immunogenicity of recombinant bcg (rbcg) constructs with different simian immunodeficiency virus (siv)gag expression ...201425080550
chronic alcohol abuse and hiv disease progression: studies with the non-human primate model.the populations at risk for hiv infection, as well as those living with hiv, overlap with populations that engage in heavy alcohol consumption. alcohol use has been associated with high-risk sexual behavior and an increased likelihood of acquiring hiv, as well as poor outcome measures of disease such as increased viral loads and declines in cd4+ t lymphocytes among those living with hiv-infections. it is difficult to discern the biological mechanisms by which alcohol use affects the virus:host i ...201425053367
type i interferon responses in rhesus macaques prevent siv infection and slow disease progression.inflammation in hiv infection is predictive of non-aids morbidity and death, higher set point plasma virus load and virus acquisition; thus, therapeutic agents are in development to reduce its causes and consequences. however, inflammation may simultaneously confer both detrimental and beneficial effects. this dichotomy is particularly applicable to type i interferons (ifn-i) which, while contributing to innate control of infection, also provide target cells for the virus during acute infection, ...201425043006
rapid seeding of the viral reservoir prior to siv viraemia in rhesus monkeys.the viral reservoir represents a critical challenge for human immunodeficiency virus type 1 (hiv-1) eradication strategies. however, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (art). here we show that the viral reservoir is seeded rapidly after mucosal simian immunodeficiency virus (siv) infection of rhesus monkeys and before systemic viraemia. we initiated suppressive art in gro ...201425042999
the rhesus rhadinovirus cd200 homologue affects immune responses and viral loads during in vivo infection.rhesus macaque rhadinovirus (rrv) is a gammaherpesvirus of rhesus macaque (rm) monkeys that is closely related to human herpesvirus 8 (hhv-8)/kaposi's sarcoma-associated herpesvirus (kshv), and it is capable of inducing diseases in simian immunodeficiency virus (siv)-infected rm that are similar to those seen in humans coinfected with hiv and hhv-8. both hhv-8 and rrv encode viral cd200 (vcd200) molecules that are homologues of cellular cd200, a membrane glycoprotein that regulates immune respon ...201424991004
targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.α4β7 integrin-expressing cd4(+) t cells preferentially traffic to gut-associated lymphoid tissue (galt) and have a key role in hiv and simian immunodeficiency virus (siv) pathogenesis. we show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with sivmac251. in treated animals that became infected, the galt was significantly protected from infecti ...201425419708
plasmodium infection reduces the volume of the viral reservoir in siv-infected rhesus macaques receiving antiretroviral therapy.previous studies indicated that plasmodium infection activates the immune system, including memory cd4+ t cells, which constitute the reservoir of human immunodeficiency virus type-1 (hiv-1). therefore, we postulated that co-infection with malaria might activate the reservoir of hiv-1. to test this hypothesis, we used a rhesus macaque model of co-infection with malaria and simian immunodeficiency virus (siv), along with antiretroviral therapy (art).201425487036
increased mucosal cd4+ t cell activation in rhesus macaques following vaccination with an adenoviral vector.the possibility that vaccination with adenovirus (adv) vectors increased mucosal t cell activation remains a central hypothesis to explain the potential enhancement of hiv acquisition within the step trial. modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (hadv-5), are not endogenous to macaques. here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [sadv-7]) enhances mucosal t cel ...201424829340
optimization of pcr for quantification of simian immunodeficiency virus genomic rna in plasma of rhesus macaques (macaca mulatta) using armored rna.quantification of plasma viral load (pvl) is used to monitor disease progression in siv-infected macaques. this study was aimed at optimizing of performance characteristics of the quantitative pcr (qpcr) pvl assay.201424266615
adenovirus serotype 26 and 35 vectors induce simian immunodeficiency virus-specific t lymphocyte responses in foreskin in rhesus monkeys.foreskin is the principal site of heterosexual hiv-1 infection in men. however, little is known about hiv-1-specific immune responses or inflammation in foreskin. to the best of our knowledge, no previous studies have assessed immune responses to candidate hiv-1 vaccines in foreskin. using the rhesus monkey model, we show that intramuscular immunization with adenovirus serotype 26 and 35 vectors expressing siv antigens elicited durable siv gag-specific cd4(+) and cd8(+) t cell responses in fores ...201424429370
postnatal acquisition of primary rhesus cytomegalovirus infection is associated with prolonged virus shedding and impaired cd4+ t lymphocyte function.although virus-specific cd4(+) t lymphocytes emerge rapidly during primary cytomegalovirus (cmv) infection in humans, they exhibit a state of prolonged functional exhaustion of unknown etiology. to investigate the suitability of rhesus macaques as a model of primary human cmv infection, we examined the virologic and immunologic features of naturally acquired primary cmv infection in rhesus macaques.201424719473
the mucosal expression pattern of interferon-ε in rhesus macaques.type i ifns play an important role in innate and adaptive immunity against viral infections. a novel type i ifn, namely ifn-ε, which can protect against vaginal transmission of hsv2 and chlamydia muridarum bacterial infection, has been described in mice and humans. nevertheless, the principle cell type and the expression pattern of ifn-ε in tissues remain uncertain. in addition, the expression of ifn-ε in indian rhesus macaques (macaca mulatta) has not been reported. here, we analyzed ifn-ε expr ...201425139290
effects of vector backbone and pseudotype on lentiviral vector-mediated gene transfer: studies in infant ada-deficient mice and rhesus monkeys.systemic delivery of a lentiviral vector carrying a therapeutic gene represents a new treatment for monogenic disease. previously, we have shown that transfer of the adenosine deaminase (ada) cdna in vivo rescues the lethal phenotype and reconstitutes immune function in ada-deficient mice. in order to translate this approach to ada-deficient severe combined immune deficiency patients, neonatal ada-deficient mice and newborn rhesus monkeys were treated with species-matched and mismatched vectors ...201424925206
transmitted/founder simian immunodeficiency virus envelope sequences in vesicular stomatitis and semliki forest virus vector immunized rhesus macaques.identification of transmitted/founder simian immunodeficiency virus (siv) envelope sequences responsible for infection may prove critical for understanding hiv/siv mucosal transmission. we used single genome amplification and phylogenetic analyses to characterize transmitted/founder sivs both in the inoculum and in immunized-infected rhesus monkeys. single genome amplification of the sivsme660 inoculum revealed a maximum diversity of 1.4%. we also noted that the consensus sequence of the challen ...201425360552
linking pig-tailed macaque major histocompatibility complex class i haplotypes and cytotoxic t lymphocyte escape mutations in simian immunodeficiency virus infection.the influence of major histocompatibility complex class i (mhc-i) alleles on human immunodeficiency virus (hiv) diversity in humans has been well characterized at the population level. mhc-i alleles likely affect viral diversity in the simian immunodeficiency virus (siv)-infected pig-tailed macaque (macaca nemestrina) model, but this is poorly characterized. we studied the evolution of siv in pig-tailed macaques with a range of mhc-i haplotypes. siv(mac251) genomes were amplified from the plasma ...201425275134
toll-like receptor 3 signaling inhibits simian immunodeficiency virus replication in macrophages from rhesus macaques.toll-like receptor 3 (tlr3) recognizes double-stranded rna and induces multiple intracellular events responsible for innate antiviral immunity against viral infections. here we demonstrate that tlr3 signaling of monocyte-derived macrophages (mdm) from rhesus monkeys by poly i:c inhibited simian immunodeficiency virus (siv) infection and replication. investigation of the mechanisms showed that tlr3 activation resulted in the induction of type i and type iii interferons (ifns) and ifn-inducible an ...201425453343
virus-host mucosal interactions during early siv rectal transmission.to deepen our understanding of early rectal transmission of hiv-1, we studied virus-host interactions in the rectal mucosa using simian immunodeficiency virus (siv)-indian rhesus macaque model and mrna deep sequencing. we found that rectal mucosa actively responded to siv as early as 3 days post-rectal inoculation (dpi) and mobilized more robust responses at 6 and 10 dpi. our results suggest that the failure of the host to contain virus replication at the portal of entry is attributable to both ...201425128762
kir2dl4 copy number variation is associated with cd4+ t-cell depletion and function of cytokine-producing nk cell subsets in siv-infected mamu-a*01-negative rhesus macaques.here, we demonstrate that kir2dl4 copy number variation (cnv) is associated with cd4(+) t-cell decline and functionality of cytokine-producing nk cells during primary simian immunodeficiency virus (siv) infection in mamu-a*01(-) indian-origin rhesus macaques, with higher kir2dl4 copy numbers being associated with a better preservation of cd4(+) t cells and an increased gamma interferon (ifn-γ) production from stimulated cytokine-producing nk cell subsets during acute sivmac251 infection. these f ...201323449795
immunogenicity of seven new recombinant yellow fever viruses 17d expressing fragments of sivmac239 gag, nef, and vif in indian rhesus macaques.an effective vaccine remains the best solution to stop the spread of human immunodeficiency virus (hiv). cellular immune responses have been repeatedly associated with control of viral replication and thus may be an important element of the immune response that must be evoked by an efficacious vaccine. recombinant viral vectors can induce potent t-cell responses. although several viral vectors have been developed to deliver hiv genes, only a few have been advanced for clinical trials. the live-a ...201323336000
transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated siv infection.a majority of individuals infected with human immunodeficiency virus (hiv) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. due to the impracticalities of conducting host-microbe systems-based studies in hiv infected patients, we have evaluated the potential of simian immunodeficiency virus (siv) infected rhesus macaques to serve as a non-human primate model for oral manifestations of hiv disease. ...201324312248
effect of semen and seminal amyloid on vaginal transmission of simian immunodeficiency virus.semen and semen-derived amyloid fibrils boost hiv infection in vitro but their impact on sexual virus transmission in vivo is unknown. here, we examined the effect of seminal plasma (sp) and semen-derived enhancer of virus infection (sevi) on vaginal virus transmission in the siv/rhesus macaque (macacca mulatta) model.201324308721
old world monkeys and new age science: the evolution of nonhuman primate systems virology.nonhuman primate (nhp) biomedical models are critical to our understanding of human health and disease, yet we are still in the early stages of developing sufficient tools to support primate genomic research that allow us to better understand the basis of phenotypic traits in nhp models of disease. a mere 7 years ago, the limited nhp transcriptome profiling that was being performed was done using complementary dna arrays based on human genome sequences, and the lack of nhp genomic information an ...201324174440
functional antagonism of rhesus macaque and chimpanzee bst-2 by hiv-1 vpu is mediated by cytoplasmic domain interactions.human immunodeficiency virus type 1 (hiv-1) vpu enhances the release of viral particles from infected cells by interfering with the function of bst-2/tetherin, a cellular protein inhibiting virus release. the vpu protein encoded by nl4-3, a widely used hiv-1 laboratory strain, antagonizes human bst-2 but not monkey or murine bst-2, leading to the conclusion that bst-2 antagonism by vpu is species specific. in contrast, we recently identified several primary vpu isolates, such as vpu of hiv-1dh12 ...201324109238
efficiency of cell-free and cell-associated virus in mucosal transmission of human immunodeficiency virus type 1 and simian immunodeficiency virus.effective strategies are needed to block mucosal transmission of human immunodeficiency virus type 1 (hiv-1). here, we address a crucial question in hiv-1 pathogenesis: whether infected donor mononuclear cells or cell-free virus plays the more important role in initiating mucosal infection by hiv-1. this distinction is critical, as effective strategies for blocking cell-free and cell-associated virus transmission may be different. we describe a novel ex vivo model system that utilizes sealed hum ...201324109227
neuroprotective maraviroc monotherapy in simian immunodeficiency virus-infected macaques: reduced replicating and latent siv in the brain.hiv-associated neurocognitive deficits remain a challenge despite suppressive combined antiretroviral therapy. given the association between hiv-induced central nervous system (cns) disease and replication of hiv in immune-activated macrophages, ccr5 antagonists may attenuate cns disease by modulating inflammatory signaling and by limiting viral replication.201324051706
limited impact of passive non-neutralizing antibody immunization in acute siv infection on viremia control in rhesus macaques.antiviral antibodies, especially those with neutralizing activity against the incoming strain, are potentially important immunological effectors to control human immunodeficiency virus (hiv) infection. while neutralizing activity appears to be central in sterile protection against hiv infection, the entity of inhibitory mechanisms via hiv and simian immunodeficiency virus (siv)-specific antibodies remains elusive. the recent hiv vaccine trial rv144 and studies in nonhuman primate models have ind ...201324039947
inhibition of cul4a neddylation causes a reversible block to samhd1-mediated restriction of hiv-1.the deoxynucleoside triphosphohydrolase samhd1 restricts retroviral replication in myeloid cells. human immunodeficiency virus type 2 (hiv-2) and a simian immunodeficiency virus from rhesus macaques (sivmac) encode vpx, a virion-packaged accessory protein that counteracts samhd1 by inducing its degradation. samhd1 is thought to work by depleting the pool of intracellular deoxynucleoside triphosphates but has also been reported to have exonuclease activity that could allow it to degrade the viral ...201323986575
early detection of simian immunodeficiency virus in the central nervous system following oral administration to rhesus macaques.the timing of hiv dissemination to the central nervous system (cns) has the potential to have important implications regarding hiv disease progression and treatment. the earlier hiv enters the cns the more difficult it might be to remove with antiretroviral therapy. alternatively, hiv may only enter the cns later in the course of disease as a result of disruption of the blood-brain-barrier. we utilized the simian immunodeficiency virus (siv) infection of rhesus macaques to evaluate the oral rout ...201323966995
dynamics of cytokine/chemokine responses in intestinal cd4+ and cd8+ t cells during acute simian immunodeficiency virus infection.loss of intestinal cd4(+) t cells was associated with decreased production of several t-helper 1 (th1) and th2 cytokines and increased production of interleukin 17 (il-17), gamma interferon (ifn-γ), ccl4, and granulocyte-macrophage colony-stimulating factor (gm-csf) by cd8(+) t cells 21 days after simian immunodeficiency virus (siv) infection in rhesus macaques. shifting of mucosal th1 to th2 or t-cytotoxic 1 (tc1) to tc2 cytokine profiles was not evident. additionally, both cd4(+) and cd8(+) t ...201323966391
generation of rhesus macaque-tropic hiv-1 clones that are resistant to major anti-hiv-1 restriction factors.human immunodeficiency virus type 1 (hiv-1) replication in macaque cells is restricted mainly by antiviral cellular apobec3, trim5α/trim5cypa, and tetherin proteins. for basic and clinical hiv-1/aids studies, efforts to construct macaque-tropic hiv-1 (hiv-1mt) have been made by us and others. although rhesus macaques are commonly and successfully used as infection models, no hiv-1 derivatives suitable for in vivo rhesus research are available to date. in this study, to obtain novel hiv-1mt clone ...201323966385
siv infection of rhesus macaques of chinese origin: a suitable model for hiv infection in humans.simian immunodeficiency virus (siv) infection of indian-origin rhesus macaques (rm) has been widely used as a well-established nonhuman primate (nhp) model for hiv/aids research. however, there have been a growing number of studies using chinese rm to evaluate immunopathogenesis of siv infection. in this paper, we have for the first time reviewed and discussed the major publications related to siv or shiv infection of chinese rm in the past decades. we have compared the differences in the pathog ...201323947613
structure-specific glial response in a macaque model of neuroaids: multivoxel proton magnetic resonance spectroscopic imaging at 3 tesla.as ~40% of persons with hiv also suffer neurocognitive decline, we sought to assess metabolic dysfunction in the brains of simian immunodeficiency virus (siv)-infected rhesus macaques, an advanced animal model, in structures involved in cognitive function. we test the hypothesis that siv-infection produces proton-magnetic resonance spectroscopic imaging (h-mrsi)-observed decline in the neuronal marker, n-acetylaspartate (naa), and elevations in the glial marker, myo-inositol (mi), and associated ...201323939235
blocking tlr7- and tlr9-mediated ifn-α production by plasmacytoid dendritic cells does not diminish immune activation in early siv infection.persistent production of type i interferon (ifn) by activated plasmacytoid dendritic cells (pdc) is a leading model to explain chronic immune activation in human immunodeficiency virus (hiv) infection but direct evidence for this is lacking. we used a dual antagonist of toll-like receptor (tlr) 7 and tlr9 to selectively inhibit responses of pdc but not other mononuclear phagocytes to viral rna prior to and for 8 weeks following pathogenic simian immunodeficiency virus (siv) infection of rhesus m ...201323935491
lack of b cell dysfunction is associated with functional, gp120-dominant antibody responses in breast milk of simian immunodeficiency virus-infected african green monkeys.the design of an effective vaccine to reduce the incidence of mother-to-child transmission (mtct) of human immunodeficiency virus (hiv) via breastfeeding will require identification of protective immune responses that block postnatal virus acquisition. natural hosts of simian immunodeficiency virus (siv) sustain nonpathogenic infection and rarely transmit the virus to their infants despite high milk virus rna loads. this is in contrast to hiv-infected women and siv-infected rhesus macaques (rhms ...201323926338
siv infection of rhesus macaques differentially impacts mononuclear phagocyte responses to virus-derived tlr agonists.during progressive simian immunodeficiency virus (siv) infection, the ability of innate mononuclear phagocytes to function when responding to the invading pathogen has yet to be determined.201323905748
loss of bone marrow nk cells during siv infection is associated with increased turnover rates and cytotoxicity but not changes in trafficking.hiv and siv infections induce nk cell dysfunction and hematopoietic defects in the bone marrow, but the effects of infection on bone marrow nk cell development and function are unknown.201323898936
interleukin-10 prevents epithelial cell apoptosis by regulating ifnγ and tnfα expression in rhesus macaque colon explants.interleukin-10 (il-10) is an important immunomodulatory cytokine that plays an obligate role in regulating inflammatory responses. here we demonstrated the role of il-10 in regulating crypts length and breadth as well as maintaining the survival of epithelial cells using rhesus colon explant cultures. anti-il-10 antibody treatment of colon explant cultures induced increased production of inflammatory cytokines/molecules like ifnγ, tnfα, cd107a and perforin as well as increased epithelial cell ap ...201323867612
high production rates sustain in vivo levels of pd-1high simian immunodeficiency virus-specific cd8 t cells in the face of rapid clearance.programmed death 1 (pd-1) expression by human/simian immunodeficiency virus (hiv/siv)-specific cd8 t cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. however, the cellular mechanisms that sustain pd-1(high) virus-specific cd8 t cell responses during chronic infection are unknown. here, we show that the pd-1(high) phenotype is associated with accelerated in vivo cd8 t cell turnover in siv-infected rhesus macaques, especially within the siv- ...201323824823
cd4+ t cells support production of simian immunodeficiency virus env antibodies that enforce cd4-dependent entry and shape tropism in vivo.cd4(+) t cells rather than macrophages are the principal cells infected by human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus (siv) in vivo. macrophage tropism has been linked to the ability to enter cells through ccr5 in conjunction with limiting cd4 levels, which are much lower on macrophages than on t cells. we recently reported that rhesus macaques (rm) experimentally depleted of cd4(+) t cells before siv infection exhibit extensive macrophage infection as well as ...201323824793
the frequency of α₄β₇(high) memory cd4⁺ t cells correlates with susceptibility to rectal simian immunodeficiency virus infection.integrin α₄β₇(high) (α₄β₇(high)) mediates the homing of cd4⁺ t cells to gut-associated lymphoid tissues, which constitute a highly favorable environment for hiv expansion and dissemination. hiv and simian immunodeficiency virus (siv) envelope proteins bind to and signal through α₄β₇(high) and during acute infection siv preferentially infects α₄β₇(high) cd4⁺ t cells. we postulated that the availability of these cells at the time of challenge could influence mucosal siv transmission and acute vira ...201323797688
immune activation and regulation in simian immunodeficiency virus-plasmodium fragile-coinfected rhesus macaques.human immunodeficiency virus (hiv) is characterized by immune activation, while chronic malaria is associated with elevated interleukin-10 (il-10) levels. how these apparently antagonizing forces interact in the coinfected host is poorly understood. using a rhesus macaque model of simian immunodeficiency virus (siv)-plasmodium fragile coinfection, we evaluated how innate immune effector cells affect the balance between immune activation and regulation. in vitro toll-like receptor (tlr) responses ...201323785209
interleukin-21 up-regulates interleukin-21r expression and interferon gamma production by cd8+ cells in shiv-infected macaques.interleukin-21 (il-21) is produced primarily by cd4+ t cells and regulates immunity against human/simian immunodeficiency virus (hiv/siv) infection. activated cd8+ cells and their secreted interferon-gamma (ifn-γ) are crucial for the control of acute hiv/siv infection. however, whether il-21 can regulate ifn-γ production by cd8+ cells remains controversial. rhesus macaques (rms, n = 8) were infected with shiv and the levels of plasma il-21, ifn-γ and the frequency of peripheral blood activated t ...201323760006
multi-functional plasmacytoid dendritic cells redistribute to gut tissues during simian immunodeficiency virus infection.the objective of this study was to determine the systemic effects of chronic simian immunodeficiency virus (siv) infection on plasmacytoid dendritic cells (pdcs). pdcs play a critical role in antiviral immunity, but current data are conflicting on whether pdcs inhibit hiv/siv replication, or, alternatively, contribute to chronic immune activation and disease. furthermore, previous pdc studies have been complicated by incomplete descriptions of generalized depletion during hiv/siv infection, and ...201323746074
influence of naturally occurring simian foamy viruses (sfvs) on siv disease progression in the rhesus macaque (macaca mulatta) model.we have investigated the influence of naturally occurring simian foamy viruses (sfvs) on simian immunodeficiency virus (siv) infection and disease in indian rhesus macaques. animals were divided into two groups based upon presence or absence of sfv; in each group, eight monkeys were injected with siv(mac239) virus obtained from a molecular clone and four were injected with medium. blood was collected every two weeks for evaluation of siv infection based upon t cell-subsets, plasma viral load, de ...201323744104
a multiplex microsphere-based immunoassay increases the sensitivity of siv-specific antibody detection in serum samples and mucosal specimens collected from rhesus macaques infected with sivmac239.results from recent hiv-1 vaccine studies have indicated that high serum antibody (ab) titers may not be necessary for ab-mediated protection, and that abs localized to mucosal sites might be critical for preventing infection. enzyme-linked immunosorbent assay (elisa) has been used for decades as the gold standard for ab measurement, though recently, highly sensitive microsphere-based assays have become available, with potential utility for improved detection of abs. in this study, we assessed t ...201323741627
laser capture microdissection assessment of virus compartmentalization in the central nervous systems of macaques infected with neurovirulent simian immunodeficiency virus.nonhuman primate-simian immunodeficiency virus (siv) models are powerful tools for studying the pathogenesis of human immunodeficiency virus type 1 (hiv-1) in the brain. our laboratory recently isolated a neuropathogenic viral swarm, sivsmh804e, a derivative of sivsme543-3, which was the result of sequential intravenous passages of viruses isolated from the brains of rhesus macaques with siv encephalitis. animals infected with sivsmh804e or its precursor (sivsmh783br) developed siv meningitis an ...201323720733
acute phase cd8+ t lymphocytes against alternate reading frame epitopes select for rapid viral escape during siv infection.cd8+ t lymphocytes (ctl) can control aids virus replication. however, natural selection favoring viral variants that escape ctl recognition is a common feature of both simian immunodeficiency virus (siv) infection of macaques and hiv infection of humans. emerging data indicate that ctl directed against alternate reading frame (arf)-derived epitopes (a.k.a. cryptic epitopes) are important components of the total virus-specific response in siv and hiv infection but the contributions of these respo ...201323671565
immunopathogenesis of simian immunodeficiency virus infection in nonhuman primates.soon after the discovery of hiv-infected humans, rhesus macaques in a colony at the new england primate research center showed similar signs of a progressive immune suppression. the discovery of the simian immunodeficiency virus (siv)-associated disease opened the door to study an aids-like illness in nonhuman primates (nhp). even after 3 decades, this animal model remains an invaluable tool to provide a greater insight into hiv immunopathogenesis. in this review, recent progress in deciphering ...201323615117
suppressed th17 levels correlate with elevated pias3, shp2, and socs3 expression in cd4 t cells during acute simian immunodeficiency virus infection.t helper 17 (th17) cells play an important role in mucosal immune homeostasis and maintaining the integrity of the mucosal epithelial barrier. loss of th17 cells has been extensively documented during human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) infections. the lack of effective repopulation of th17 cells has been associated with chronic immune activation mediated by the translocation of microbial products. using ex vivo analysis of purified peripheral blood cd4 t c ...201323596301
t cells target apobec3 proteins in human immunodeficiency virus type 1-infected humans and simian immunodeficiency virus-infected indian rhesus macaques.apobec3 proteins mediate potent antiretroviral activity by hypermutating the retroviral genome during reverse transcription. to counteract apobec3 and gain a replicative advantage, lentiviruses such as human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus (siv) have evolved the vif protein, which targets apobec3 proteins for proteasomal degradation. however, the proteasome plays a critical role in the generation of t cell peptide epitopes. whether vif-mediated destruction ...201323536679
rhesus macaque lymph node pd-1(hi)cd4+ t cells express high levels of cxcr5 and il-21 and display a ccr7(lo)icos+bcl6+ t-follicular helper (tfh) cell phenotype.cd4 t follicular helper (tfh) cells play a unique and essential role in the generation of b cell responses in the lymph node microenvironment. here we sought to determine if differential expression of pd-1 could be used to delineate tfh cells in rhesus macaque lymph nodes (ln). cd3(+)cd4(+) t cells were found to harbor a unique subset of cells that expressed the program death-1 (pd-1) receptor at significantly high levels that were enriched in the ln compartment as compared to peripheral blood. ...201323527264
mucosal priming with a replicating-vaccinia virus-based vaccine elicits protective immunity to simian immunodeficiency virus challenge in rhesus monkeys.mucosal surfaces are not targeted by most human immunodeficiency virus type 1 (hiv-1) vaccines, despite being major routes for hiv-1 transmission. here we report a novel vaccination regimen consisting of a mucosal prime with a modified replicating vaccinia virus tiantan strain (mvtt(sivgpe)) and an intramuscular boost with a nonreplicating adenovirus strain (ad5(sivgpe)). this regimen elicited robust cellular immune responses with enhanced magnitudes, sustainability, and polyfunctionality, as we ...201323487457
cytotoxic capacity of siv-specific cd8(+) t cells against primary autologous targets correlates with immune control in siv-infected rhesus macaques.although the study of non-human primates has resulted in important advances for understanding hiv-specific immunity, a clear correlate of immune control over simian immunodeficiency virus (siv) replication has not been found to date. in this study, cd8(+) t-cell cytotoxic capacity was examined to determine whether this function is a correlate of immune control in the rhesus macaque (rm) siv infection model as has been suggested in chronic hiv infection. sivmac251-infected human reverse transcrip ...201323468632
heterogeneity in neutralization sensitivities of viruses comprising the simian immunodeficiency virus sivsme660 isolate and vaccine challenge stock.the sooty mangabey-derived simian immunodeficiency virus (siv) strain e660 (sivsme660) is a genetically heterogeneous, pathogenic isolate that is commonly used as a vaccine challenge strain in the nonhuman primate (nhp) model of human immunodeficiency virus type 1 (hiv-1) infection. though it is often employed to assess antibody-based vaccine strategies, its sensitivity to antibody-mediated neutralization has not been well characterized. here, we utilize single-genome sequencing and infectivity ...201323468494
global gray and white matter metabolic changes after simian immunodeficiency virus infection in cd8-depleted rhesus macaques: proton mrs imaging at 3 t.to test the hypotheses that global decreased neuro-axonal integrity reflected by decreased n-acetylaspartate (naa) and increased glial activation reflected by an elevation in its marker, the myo-inositol (mi), present in a cd8-depleted rhesus macaque model of hiv-associated neurocognitive disorders. to this end, we performed quantitative mri and 16 × 16 × 4 multivoxel proton mrs imaging (te/tr = 33/1400 ms) in five macaques pre- and 4-6 weeks post-simian immunodeficiency virus infection. absolut ...201323418159
peptide-binding motifs associated with mhc molecules common in chinese rhesus macaques are analogous to those of human hla supertypes and include hla-b27-like alleles.chinese rhesus macaques are of particular interest in simian immunodeficiency virus/human immunodeficiency virus (siv/hiv) research as these animals have prolonged kinetics of disease progression to acquired immunodeficiency syndrome (aids), compared to their indian counterparts, suggesting that they may be a better model for hiv. nevertheless, the specific mechanism(s) accounting for these kinetics remains unclear. the study of major histocompatibility complex (mhc) molecules, including their m ...201323417323
effect of bacterial pneumonia on lung simian immunodeficiency virus (siv) replication in alcohol consuming siv-infected rhesus macaques.opportunistic infections in human immunodeficiency virus (hiv)-infected persons have been shown to increase the rate of hiv replication. in populations where prophylaxis against pneumocystis pneumonia is utilized, bacterial pneumonia is now the leading cause of lower respiratory tract infection in hiv+ patients. our prior studies have shown that chronic alcohol consumption in demarcated simian immunodeficiency virus (siv)-infected rhesus macaques increases plasma viral load set point and acceler ...201323414480
cutting edge: novel vaccination modality provides significant protection against mucosal infection by highly pathogenic simian immunodeficiency virus.vaccine-induced protection against infection by hiv or highly pathogenic and virulent siv strains has been limited. in a proof-of-concept study, we show that a novel vaccine approach significantly protects rhesus macaques from mucosal infection by the highly pathogenic strain sivmac251. we vaccinated three cohorts of 12 macaques each with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-ig. cohort 1 was vaccinated with cells secreting gp96(siv)ig carryin ...201323401588
effect of combination antiretroviral therapy on chinese rhesus macaques of simian immunodeficiency virus infection.definitive treatment of hiv infection remains a critical but elusive goal, with persistence of residual virus even in the face of prolonged administration of suppressive combination antiretroviral treatment (cart) providing a source for recrudescent infection if treatment is stopped. characterization of the residual virus and devising strategies to target it for eradication are key goals in hiv treatment research. indian rhesus macaques (in-rm) infected with sivmac have been widely used in such ...201323387294
a novel protective mhc-i haplotype not associated with dominant gag-specific cd8+ t-cell responses in sivmac239 infection of burmese rhesus macaques.several major histocompatibility complex class i (mhc-i) alleles are associated with lower viral loads and slower disease progression in human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) infections. immune-correlates analyses in these mhc-i-related hiv/siv controllers would lead to elucidation of the mechanism for viral control. viral control associated with some protective mhc-i alleles is attributed to cd8+ t-cell responses targeting gag epitopes. we have been trying t ...201323342126
virus-encoded tlr ligands reveal divergent functional responses of mononuclear phagocytes in pathogenic simian immunodeficiency virus infection.the role of mononuclear phagocytes in the pathogenesis or control of hiv infection is unclear. in this study, we monitored the dynamics and function of dendritic cells (dc) and monocytes/macrophages in rhesus macaques acutely infected with pathogenic sivmac251 with and without antiretroviral therapy (art). siv infection was associated with monocyte mobilization and recruitment of plasmacytoid dc (pdc) and macrophages to lymph nodes, which did not occur with art treatment. sivmac251 single-strand ...201323338235
Refresh
firstprev
12345678910...
nextlast
Displaying items 201 - 300 of 1723