| 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, ... | 2014 | 25362178 |
| 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 ... | 2014 | 25348621 |
| 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 ... | 2014 | 25296195 |
| 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 ... | 2014 | 25282469 |
| 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 ... | 2014 | 25264057 |
| 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 ... | 2014 | 25257285 |
| antifibrotic therapy in simian immunodeficiency virus infection preserves cd4+ t-cell populations and improves immune reconstitution with antiretroviral therapy. | even with prolonged antiretroviral therapy (art), many human immunodeficiency virus-infected individuals have <500 cd4(+) t cells/µl, and cd4(+) t cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical t-cell zone (tz) that impairs homeostatic mechanisms required for t-cell survival. we therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased tz fibrosis would improve reconstitution of pe ... | 2015 | 25246534 |
| spatiotemporal dynamics of simian immunodeficiency virus brain infection in cd8+ lymphocyte-depleted rhesus macaques with neuroaids. | despite the success of combined antiretroviral therapy in controlling viral replication in human immunodeficiency virus (hiv)-infected individuals, hiv-associated neurocognitive disorders, commonly referred to as neuroaids, remain a frequent and poorly understood complication. infection of cd8(+) lymphocyte-depleted rhesus macaques with the sivmac251 viral swarm is a well-established rapid disease model of neuroaids that has provided critical insight into hiv-1-associated neurocognitive disorder ... | 2014 | 25205684 |
| a discrete-time survival model with random effects for designing and analyzing repeated low-dose challenge experiments. | repeated low-dose (rld) challenge designs are important in hiv vaccine research. current methods for rld designs rely heavily on an assumption of homogeneous risk of infection among animals, which, upon violation, can lead to invalid inferences and underpowered study designs. we propose to fit a discrete-time survival model with random effects that allows for heterogeneity in the risk of infection among animals and allows for predetermined challenge dose changes over time. based on this model, w ... | 2015 | 25190513 |
| 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 ... | 2014 | 25187546 |
| 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 ... | 2014 | 25182644 |
| 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 ... | 2014 | 25165117 |
| 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 ... | 2014 | 25143442 |
| 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 ... | 2014 | 25135832 |
| 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 ... | 2014 | 25113915 |
| 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 ... | 2014 | 25102373 |
| 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. | 2014 | 25082291 |
| 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 ... | 2014 | 25080550 |
| 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 ... | 2014 | 25053367 |
| 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, ... | 2014 | 25043006 |
| 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 ... | 2014 | 25042999 |
| cd8+ t cells maintain suppression of simian immunodeficiency virus in the central nervous system. | human immunodeficiency virus (hiv) accesses the brain early in infection and can lead to neurocognitive disorders. the brain can also serve as a viral reservoir, but how virus is controlled in the brain is unknown. to examine this, cd8-depleting monoclonal antibody was injected into the cerebrospinal fluid of rhesus monkeys with chronic simian immunodeficiency virus (siv) infection. this treatment led to the rapid increase of siv in the brain. virus in the brain is maintained by active suppressi ... | 2015 | 25035516 |
| 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 ... | 2014 | 24970236 |
| 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 ... | 2014 | 24920807 |
| 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 ... | 2014 | 24920805 |
| 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. | 2014 | 24918575 |
| 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 ... | 2014 | 24907411 |
| 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 ... | 2014 | 24902876 |
| 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 ... | 2014 | 24899503 |
| 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 ... | 2014 | 24884551 |
| 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 ... | 2014 | 24807714 |
| 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 ... | 2014 | 24807713 |
| 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 ... | 2014 | 24777106 |
| 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 ... | 2014 | 24743648 |
| 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 ... | 2014 | 24740505 |
| 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 ... | 2014 | 24709063 |
| rhesus cytomegalovirus (macacine herpesvirus 3)-associated facial neuritis in simian immunodeficiency virus-infected rhesus macaques (macaca mulatta). | peripheral neuropathies are common sequelae to human immunodeficiency virus (hiv) infection in humans and are due to a variety of mechanisms, including direct antiretroviral toxicity, hiv-mediated damage, immune-mediated disorders, and opportunistic viral infections. rhesus macaques (macaca mulatta) infected with simian immunodeficiency virus (siv) remain the most consistent animal model for unraveling the pathogenesis of lentiviral-associated disease and its associated opportunistic infections. ... | 2015 | 24686387 |
| 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 ... | 2014 | 24684292 |
| 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 ... | 2014 | 24651676 |
| 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. | 2014 | 24614087 |
| 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 ... | 2014 | 24586674 |
| 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. | 2014 | 24521395 |
| 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(+ ... | 2014 | 24501416 |
| 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 ... | 2014 | 24498008 |
| 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 ... | 2014 | 24464410 |
| 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 ... | 2014 | 24418547 |
| 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 ... | 2014 | 24400995 |
| 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 ... | 2014 | 24309114 |
| 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. | 2013 | 24308721 |
| a vaccine against ccr5 protects a subset of macaques upon intravaginal challenge with simian immunodeficiency virus sivmac251. | as an alternative to targeting human immunodeficiency virus (hiv), we have developed vaccines targeting ccr5, a self-protein critically involved in hiv replication and pathogenesis. by displaying peptides derived from ccr5 at high density on the surface of virus-like particles, we can efficiently induce high-titer igg antibodies against this self-molecule. here, we investigated whether prophylactic immunization of rhesus macaques with a particle-based vaccine targeting two regions of macaque ccr ... | 2014 | 24307581 |
| transient increase of interferon-stimulated genes and no clinical benefit by chloroquine treatment during acute simian immunodeficiency virus infection of macaques. | simian immunodeficiency virus (siv) infection leads to aids in experimentally infected rhesus macaques similarly to hiv-infected humans. in contrast, siv infection of natural hosts is characterized by a down-regulation of innate acute responses to the virus within a few weeks of infection and results in limited pathology. chloroquine (cq) has been used in the treatment or prevention of malaria and has recently been shown to cause a decrease of immune activation and cd4 cell loss in hiv-infected ... | 2014 | 24251542 |
| 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 ... | 2013 | 24174440 |
| poly-proline motif in hiv-2 vpx is critical for its efficient translation. | human immunodeficiency virus type 2 (hiv-2) carries an accessory protein vpx that is important for viral replication in natural target cells. in its c-terminal region, there is a highly conserved poly-proline motif (ppm) consisting of seven consecutive prolines, encoded in a poly-pyrimidine tract. we have previously shown that ppm is critical for vpx expression and viral infectivity. to elucidate the molecular basis underlying this observation, we analysed the expression of vpx proteins with var ... | 2014 | 24114794 |
| 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 ... | 2013 | 24109238 |
| 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 ... | 2013 | 24109227 |
| 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. | 2013 | 24051706 |
| 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 ... | 2013 | 24039947 |
| 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 ... | 2013 | 23986575 |
| 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 ... | 2013 | 23966995 |
| 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 ... | 2013 | 23966391 |
| 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 ... | 2013 | 23966385 |
| 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 ... | 2013 | 23947613 |
| 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 ... | 2013 | 23939235 |
| 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 ... | 2013 | 23935491 |
| 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 ... | 2013 | 23926338 |
| 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. | 2013 | 23905748 |
| 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. | 2013 | 23898936 |
| 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 ... | 2013 | 23867612 |
| 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- ... | 2013 | 23824823 |
| 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 ... | 2013 | 23824793 |
| 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 ... | 2013 | 23797688 |
| il-21-producer cd4+ t cell kinetics during primary simian immunodeficiency virus infection. | il-21 signaling is important for t cell and b cell-mediated clearance of chronic viral infections. while non-cognate follicular helper cd4+ t cells (tfh) are indicated to be pivotal in providing il-21-mediated help to activated b cells within germinal centers, how this signaling may be disrupted in early aids virus infection is not clear. in this study, we assessed the lineage and kinetics of peripheral blood il-21-producing cd4+ t cells in primary simian immunodeficiency virus (siv) infection o ... | 2016 | 23791954 |
| 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 ... | 2013 | 23785209 |
| 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 ... | 2013 | 23760006 |
| 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 ... | 2013 | 23746074 |
| 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 ... | 2013 | 23744104 |
| 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 ... | 2013 | 23741627 |
| 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 ... | 2013 | 23720733 |
| 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 ... | 2013 | 23671565 |
| 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 ... | 2013 | 23615117 |
| 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 ... | 2013 | 23596301 |
| 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 ... | 2013 | 23536679 |
| 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. ... | 2013 | 23527264 |
| 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 ... | 2013 | 23487457 |
| 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 ... | 2013 | 23468632 |
| 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 ... | 2013 | 23468494 |
| 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 ... | 2013 | 23418159 |
| 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 ... | 2013 | 23417323 |
| 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 ... | 2013 | 23414480 |
| 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 ... | 2013 | 23401588 |
| 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 ... | 2013 | 23387294 |
| 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 ... | 2013 | 23342126 |
| 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 ... | 2013 | 23338235 |
| microbial translocation in the pathogenesis of hiv infection and aids. | in pathogenic simian immunodeficiency virus (siv) and human immunodeficiency virus (hiv) infections, the translocation of microbial products from the gastrointestinal (gi) tract to portal and systemic circulation has been proposed as a major driver of the chronic immune activation that is associated with disease progression. consistently, microbial translocation is not present in nonpathogenic siv infections of natural host species. in vivo studies demonstrated that hiv/siv-associated microbial ... | 2013 | 23297256 |
| evidence for a different susceptibility of primate lentiviruses to type i interferons. | type i interferons induce a complex transcriptional program that leads to a generalized antiviral response against a large panel of viruses, including human immunodeficiency virus type 1 (hiv-1). however, despite the fact that interferons negatively regulate hiv-1 ex vivo, a chronic interferon state is linked to the progression of aids and to robust viral replication, rather than protection, in vivo. to explain this apparent contradiction, we hypothesized that hiv-1 may have evolved a partial re ... | 2013 | 23255800 |
| efficient mucosal transmissibility but limited pathogenicity of r5 shiv sf162p3n in chinese-origin rhesus macaques. | infection of rhesus macaques (rms) of indian origin with simian immunodeficiency virus or simian-hiv (shiv) provided powerful tools to study hiv-1 transmission and disease and for testing the efficacy of novel drugs, vaccines, and prevention strategies. in developing alternative nonhuman primate aids models for the ccr5 (r5)-tropic shivsf162p3n, we characterized virus transmission and infection in chinese-origin rms. | 2013 | 23221980 |
| alternative serotype adenovirus vaccine vectors elicit memory t cells with enhanced anamnestic capacity compared to ad5 vectors. | the failure of the adenovirus serotype 5 (ad5) vector-based human immunodeficiency virus type 1 (hiv-1) vaccine in the step study has led to the development of adenovirus vectors derived from alternative serotypes, such as ad26, ad35, and ad48. we have recently demonstrated that vaccines using alternative-serotype ad vectors confer partial protection against stringent simian immunodeficiency virus (siv) challenges in rhesus monkeys. however, phenotypic differences between the t cell responses el ... | 2013 | 23152535 |
| loss of a tyrosine-dependent trafficking motif in the simian immunodeficiency virus envelope cytoplasmic tail spares mucosal cd4 cells but does not prevent disease progression. | a hallmark of pathogenic simian immunodeficiency virus (siv) and human immunodeficiency virus (hiv) infections is the rapid and near-complete depletion of mucosal cd4(+) t lymphocytes from the gastrointestinal tract. loss of these cells and disruption of epithelial barrier function are associated with microbial translocation, which has been proposed to drive chronic systemic immune activation and disease progression. here, we evaluate in rhesus macaques a novel attenuated variant of pathogenic s ... | 2013 | 23152518 |
| characterization of the major histocompatibility complex class i a alleles in cynomolgus macaques of vietnamese origin. | cynomolgus macaques (macaca fascicularis, mafa) have emerged as an important animal model for infectious disease and transplantation research. extensive characterization of their major histocompatibility complex (mhc) polymorphism regions therefore becomes urgently required. in this study, we identified 41 mhc class i a nucleotide sequences in 34 unrelated cynomolgus macaques of vietnamese origin farmed in southern china, including eight novel mafa-a sequences. we found two sequences with perfec ... | 2012 | 23137320 |
| transcriptional profiling of experimental cd8(+) lymphocyte depletion in rhesus macaques infected with simian immunodeficiency virus sivmac239. | cd8(+) t cells inhibit virus replication in siv-infected rhesus macaques. however, it is unclear to what extent the viral suppression mediated by cd8(+) t cells reflects direct killing of infected cells as opposed to indirect, noncytolytic mechanisms. in this study, we used functional genomics to investigate noncytolytic mechanisms of in vivo viral suppression mediated by cd8(+) lymphocytes. eight chronically sivmac239-infected rhesus macaques underwent cd8(+) lymphocyte depletion, and rna from ... | 2013 | 23097439 |