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reduced inflammation and lymphoid tissue immunopathology in rhesus macaques receiving anti-tumor necrosis factor treatment during primary simian immunodeficiency virus infection.human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) infections induce robust, generalized inflammatory responses that begin during acute infection and lead to pathological systemic immune activation, fibrotic damage of lymphoid tissues, and cd4⁺ t-cell loss, pathogenic processes that contribute to disease progression.201323087435
distinct evolutionary pressures underlie diversity in simian immunodeficiency virus and human immunodeficiency virus lineages.simian immunodeficiency virus (siv) infection of rhesus macaques causes immune depletion and disease closely resembling human aids and is well recognized as the most relevant animal model for the human disease. experimental investigations of viral pathogenesis and vaccine protection primarily involve a limited set of related viruses originating in sooty mangabeys (sivsmm). the diversity of human immunodeficiency virus type 1 (hiv-1) has evolved in humans in about a century; in contrast, siv isol ...201223055550
loss of effector and anti-inflammatory natural killer t lymphocyte function in pathogenic simian immunodeficiency virus infection.chronic immune activation is a key determinant of aids progression in hiv-infected humans and simian immunodeficiency virus (siv)-infected macaques but is singularly absent in siv-infected natural hosts. to investigate whether natural killer t (nkt) lymphocytes contribute to the differential modulation of immune activation in aids-susceptible and aids-resistant hosts, we compared nkt function in macaques and sooty mangabeys in the absence and presence of siv infection. cynomolgus macaques had si ...201223028326
vaccine-induced cd8+ t cells control aids virus replication.developing a vaccine for human immunodeficiency virus (hiv) may be aided by a complete understanding of those rare cases in which some hiv-infected individuals control replication of the virus. most of these elite controllers express the histocompatibility alleles hla-b*57 or hla-b*27 (ref. 3). these alleles remain by far the most robust associations with low concentrations of plasma virus, yet the mechanism of control in these individuals is not entirely clear. here we vaccinate indian rhesus m ...201223023123
neutralizing capacity of monoclonal antibodies that recognize peptide sequences underlying the carbohydrates on gp41 of simian immunodeficiency virus.extensive glycosylation of the envelope spikes of human and simian immunodeficiency virus (hiv and siv) is an important factor for the resistance of these viruses to neutralization by antibodies. sivmac239 gp41 has three closely spaced sites for n-linked carbohydrate attachment. rhesus macaques experimentally infected with mutant versions of sivmac239 lacking two or three of these carbohydrate sites developed strong serum reactivity against mutated peptide sequences at the site of these glycosyl ...201222993152
simian immunodeficiency virus interactions with macaque dendritic cells.this chapter summarizes advances in the following areas: (1) dendritic cell (dc)-mediated simian immunodeficiency virus (siv) transmission, (2) role of dcs in innate and adaptive immunity against siv, and (3) approaches to harness dc function to induce anti-siv responses. the nonhuman primate (nhp) model of human immunodeficiency virus (hiv) infection in rhesus macaques and other asian nhp species is highly relevant to advance the understanding of virus-host interactions critical for transmissio ...201322975875
dynamics of memory b-cell populations in blood, lymph nodes, and bone marrow during antiretroviral therapy and envelope boosting in simian immunodeficiency virus sivmac251-infected rhesus macaques.human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) infection causes b-cell dysregulation and the loss of memory b cells in peripheral blood mononuclear cells (pbmc). these effects are not completely reversed by antiretroviral treatment (art). to further elucidate b-cell changes during chronic siv infection and treatment, we investigated memory b-cell subpopulations and plasma cells/plasmablasts (pc/pb) in blood, bone marrow, and lymph nodes of rhesus macaques during art and u ...201222973034
partial protection of shiv-infected chinese rhesus macaques against super-infection with heterologous shiv isolate.many studies have revealed a protective effect of infection with simian immunodeficiency virus (siv) or simian-human immunodeficiency virus (shiv) against subsequent infection by a related immunodeficiency virus. however, whether a protective response can be induced by an infection with an immunodeficiency virus is still currently debated in the hiv-1 vaccine field. the aim of this study was to evaluate the protection against shiv challenge in chinese macaques that had been inoculated with shivs ...201222954309
adcc develops over time during persistent infection with live-attenuated siv and is associated with complete protection against siv(mac)251 challenge.live-attenuated strains of simian immunodeficiency virus (siv) routinely confer apparent sterilizing immunity against pathogenic siv challenge in rhesus macaques. understanding the mechanisms of protection by live-attenuated siv may provide important insights into the immune responses needed for protection against hiv-1. here we investigated the development of antibodies that are functional against neutralization-resistant siv challenge strains, and tested the hypothesis that these antibodies ar ...201222927823
preclinical evaluation of hiv eradication strategies in the simian immunodeficiency virus-infected rhesus macaque: a pilot study testing inhibition of indoleamine 2,3-dioxygenase.even in the setting of maximally suppressive antiretroviral therapy (art), hiv persists indefinitely. several mechanisms might contribute to this persistence, including chronic inflammation and immune dysfunction. in this study, we have explored a preclinical model for the evaluation of potential interventions that might serve to eradicate or to minimize the level of persistent virus. given data that metabolic products of the inducible enzyme indoleamine 2,3-dioxygeanse (ido) might foster inflam ...201322924680
high-efficiency transduction of rhesus hematopoietic repopulating cells by a modified hiv1-based lentiviral vector.human immunodeficiency virus type 1 (hiv1) vectors poorly transduce rhesus hematopoietic cells due to species-specific restriction factors, including the tripartite motif-containing 5 isoformα (trim5α) which targets the hiv1 capsid. we previously developed a chimeric hiv1 (χhiv) vector system wherein the vector genome is packaged with the simian immunodeficiency virus (siv) capsid for efficient transduction of both rhesus and human cd34(+) cells. to evaluate whether χhiv vectors could efficientl ...201222871664
risk of immunodeficiency virus infection may increase with vaccine-induced immune response.to explore the efficacy of novel complementary prime-boost immunization regimens in a nonhuman primate model for hiv infection, rhesus monkeys primed by different dna vaccines were boosted with virus-like particles (vlp) and then challenged by repeated low-dose rectal exposure to simian immunodeficiency virus (siv). characteristic of the cellular immune response after the vlp booster immunization were high numbers of siv-specific, gamma interferon-secreting cells after stimulation with inactivat ...201222811518
nk and cd4+ t cell cooperative immune responses correlate with control of disease in a macaque simian immunodeficiency virus infection model.control of infectious disease may be accomplished by successful vaccination or by complex immunologic and genetic factors favoring ag-specific multicellular immune responses. using a rhesus macaque model, we evaluated ag-specific t cell-dependent nk cell immune responses in siv-infected macaques, designated "controlling" or "noncontrolling" based on long-term chronic viremia levels, to determine whether nk cell effector functions contribute to control of siv infection. we observed that gag stimu ...201222798665
systemic vaccination induces clonally diverse siv-specific cd8+ t-cell populations in systemic and mucosal compartments.an hiv-1 vaccine must elicit a clonally diverse virus-specific cd8+ t-cell response to contain mutant virus forms, and these responses must be present in mucosal tissues, which are the site of early hiv-1 replication. we show that systemic delivery of prototype vaccine vectors in rhesus monkeys induced siv (simian immunodeficiency virus)-specific cd8+ t-cell responses in systemic and mucosal compartments with comparable clonal compositions. although clonal sharing was maintained between the peri ...201322763409
gag-specific cellular immunity determines in vitro viral inhibition and in vivo virologic control following simian immunodeficiency virus challenges of vaccinated rhesus monkeys.a comprehensive vaccine for human immunodeficiency virus type 1 (hiv-1) would block hiv-1 acquisition as well as durably control viral replication in breakthrough infections. recent studies have demonstrated that env is required for a vaccine to protect against acquisition of simian immunodeficiency virus (siv) in vaccinated rhesus monkeys, but the antigen requirements for virologic control remain unclear. here, we investigate whether cd8(+) t lymphocytes from vaccinated rhesus monkeys mediate v ...201222761379
sequential evolution and escape from neutralization of simian immunodeficiency virus sivsme660 clones in rhesus macaques.simian immunodeficiency virus (siv) infection of rhesus macaques has become an important surrogate model for evaluating hiv vaccine strategies. the extreme resistance to neutralizing antibody (nab) of many commonly used strains, such as sivmac251/239 and sivsme543-3, limits their potential relevance for evaluating the role of nab in vaccine protection. in contrast, sivsme660 is an uncloned virus that appears to be more sensitive to neutralizing antibody. to evaluate the role of nab in this model ...201222696650
plasmodium inui infection reduces the efficacy of a simian immunodeficiency virus dna vaccine in a rhesus macaque model through alteration of the vaccine-induced immune response.human immunodeficiency virus type 1 and malaria are co-endemic in many areas. we evaluated the effects of plasmodium inui infection on the performance of a simian immunodeficiency virus (siv) dna vaccine. rhesus macaques were infected with p. inui by transfusion of whole blood from a persistently infected animal. animals with and animals without p. inui infection were then vaccinated 4 times with an siv dna vaccine encoding sivgag, sivpol, and sivenv. animals were subsequently challenged with th ...201222693228
electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins.human immunodeficiency virus type 2 (hiv-2) and simian immunodeficiency virus isolated from a macaque monkey (sivmac) are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (sivsm). despite their close similarity in genome structure, hiv-2 and sivmac show different sensitivities to trim5α, a host restriction factor against retroviruses. the replication of hiv-2 strains is potently restricted by rhesus (rh) monkey trim5α, while that of sivmac strain 239 (si ...201222679444
methamphetamine and inflammatory cytokines increase neuronal na+/k+-atpase isoform 3: relevance for hiv associated neurocognitive disorders.methamphetamine (meth) abuse in conjunction with human immunodeficiency virus (hiv) exacerbates neuropathogenesis and accelerates neurocognitive impairments in the central nervous system (cns), collectively termed hiv associated neurocognitive disorders (hand). since both hiv and meth have been implicated in altering the synaptic architecture, this study focused on investigating alterations in synaptic proteins. employing a quantitative proteomics approach on synaptosomes isolated from the cauda ...201222662178
siv replication in the infected rhesus macaque is limited by the size of the preexisting th17 cell compartment.the mechanisms by which some hiv-infected subjects resist disease progression, whereas others progress rapidly, are incompletely understood. viral and host genetic factors, such as nef deletions and major histocompatibility complex alleles, explain a portion of the observed variability. however, it has been difficult to identify host immune functions that may be present before infection and that allow resistance to lentiviral disease progression. here, we show that simian immunodeficiency virus ...201222649090
accelerated heterologous adenovirus prime-boost siv vaccine in neonatal rhesus monkeys.a pediatric human immunodeficiency virus type 1 (hiv-1) vaccine would be desirable to protect infants against hiv-1 transmission from breast-feeding. such a vaccine would need to induce protective immunity at mucosal surfaces in neonates as soon as possible after birth. recombinant adenovirus (rad) vectors have been shown to elicit potent systemic and mucosal virus-specific immune responses in adult nonhuman primates and humans, but these vectors have not previously been comprehensively studied ...201222593160
antiviral antibodies and t cells are present in the foreskin of simian immunodeficiency virus-infected rhesus macaques.no information exists regarding immune responses to human immunodeficiency virus (hiv) infection in the foreskin or glans of the human penis, although this is a key tissue for hiv transmission. to address this gap, we characterized antiviral immune responses in foreskin of male rhesus macaques (rms) inoculated with simian immunodeficiency virus (siv) strain sivmac251 by penile foreskin exposure. we found a complete population of immune cells in the foreskin and glans of normal rms, although b ce ...201222532691
envelope variable region 4 is the first target of neutralizing antibodies in early simian immunodeficiency virus mac251 infection of rhesus monkeys.a major goal of aids vaccine development is to design vaccination strategies that can elicit broad and potent protective antibodies. the initial viral targets of neutralizing antibodies (nabs) early after human or simian immunodeficiency virus (hiv/siv) infection are not known. the identification of early nab epitopes that induce protective immunity or retard the progression of disease is important for aids vaccine development. the aim of this study was to determine the env residues targeted by ...201222532675
immunization with recombinant macaque major histocompatibility complex class i and ii and human immunodeficiency virus gp140 inhibits simian-human immunodeficiency virus infection in macaques.genetic, epidemiological and experimental evidence suggest that the major histocompatibility complex (mhc) is critical in controlling human immunodeficiency virus (hiv) infection. the objectives of this study were to determine whether novel recombinant mamu mhc constructs would elicit protection against rectal challenge with heterologous simian-human immunodeficiency virus (shiv) strain sf162.p4 in rhesus macaques. mamu class i and ii gene products were linked together with hiv gp140, simian imm ...201222492918
naive t cells are dispensable for memory cd4+ t cell homeostasis in progressive simian immunodeficiency virus infection.the development of aids in chronic hiv/simian immunodeficiency virus (siv) infection has been closely linked to progressive failure of cd4(+) memory t cell (t(m)) homeostasis. cd4(+) naive t cells (t(n)) also decline in these infections, but their contribution to disease progression is less clear. we assessed the role of cd4(+) t(n) in siv pathogenesis using rhesus macaques (rms) selectively and permanently depleted of cd4(+) t(n) before siv infection. cd4(+) t(n)-depleted and cd4(+) t(n)-replet ...201222451717
enhanced pulmonary arteriopathy in simian immunodeficiency virus-infected macaques exposed to morphine.hiv-associated pulmonary arterial hypertension (pah) is likely a more prevalent noninfectious complication of aids than previously recognized. furthermore, the majority of hiv-pah cases occur in individuals with a history of intravenous drug use. in this study we used a simian immunodeficiency (siv) macaque model and a primary cell-culture system to investigate the association between drug abuse and hiv infection in hiv-pah development.201222447963
role of human trim5α in intrinsic immunity.human immunodeficiency virus (hiv) has a very narrow host range. hiv type 1 (hiv-1) does not infect old world monkeys, such as the rhesus monkey (rh). rh trim5α was identified as a factor that confers resistance, intrinsic immunity, to hiv-1 infection. unfortunately, human trim5α is almost powerless to restrict hiv-1. however, human trim5α potently restricts n-tropic murine leukemia viruses (mlv) but not b-tropic mlv, indicating that human trim5α represents the restriction factor previously desi ...201222435067
plasma gelsolin accumulates in macrophage nodules in brains of simian immunodeficiency virus infected rhesus macaques.plasma gelsolin (pgsn), an isoform 1, is secreted by various types of cells in the central nervous system (cns) and periphery, but not by the liver. pgsn circulates in blood and cerebrospinal fluid (csf); however, its concentration in csf is approximately twenty times lower than in plasma. it has been shown that several types of cells such as oligodendrocytes, neurons, and/or astrocytes contribute to the overall pool of pgsn in the cns. further, it has been postulated that pgsn plays multiple ro ...201222403026
spatial alterations between cd4(+) t follicular helper, b, and cd8(+) t cells during simian immunodeficiency virus infection: t/b cell homeostasis, activation, and potential mechanism for viral escape.hiv/siv infections induce chronic immune activation with remodeling of lymphoid architecture and hypergammaglobulinemia, although the mechanisms leading to such symptoms remain to be fully elucidated. moreover, lymph nodes have been highlighted as a predilection site for siv escape in vivo. following 20 rhesus macaques infected with sivmac239 as they progress from pre-infection to acute and chronic infection, we document for the first time, to our knowledge, the local dynamics of t follicular he ...201222387550
samhd1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.samhd1 restricts the infection of dendritic and other myeloid cells by human immunodeficiency virus type 1 (hiv-1), but in lentiviruses of the simian immunodeficiency virus of sooty mangabey (sivsm)-hiv-2 lineage, samhd1 is counteracted by the virion-packaged accessory protein vpx. here we found that samhd1 restricted infection by hydrolyzing intracellular deoxynucleoside triphosphates (dntps), lowering their concentrations to below those required for the synthesis of the viral dna by reverse tr ...201222327569
trim5α and species tropism of hiv/siv.human immunodeficiency virus type 1 (hiv-1) infects humans and chimpanzees but not old world monkeys (owms) such as the rhesus monkey (rh) and cynomolgus monkey (cm). hiv-1 efficiently enters cells of owms but encounters a block before reverse transcription. this narrow host range is attributed to a barrier in the host cell. in 2004, the screening of a rh cdna library identified tripartite motif 5α (trim5α) as a cellular antiviral factor. trim5α is one of splicing variants produced by trim5 gene ...201222291694
vaccine protection against acquisition of neutralization-resistant siv challenges in rhesus monkeys.preclinical studies of human immunodeficiency virus type 1 (hiv-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (siv) challenges in rhesus monkeys. adenovirus/poxvirus and adenovirus/adenovirus-vecto ...201222217938
spontaneous cervicovaginal lesions and immune cell infiltrates in nonhuman primates.nonhuman primates, particularly rhesus macaques (macaca mulatta), provide important model systems for studying human reproductive infectious diseases such as human immunodeficiency virus, human papillomavirus, and chlamydia spp. an understanding of the spectrum of spontaneous cervical disease provides essential context for interpreting experimental disease outcomes in the female reproductive tract. this retrospective study characterizes the incidence of inflammatory and/or proliferative cervicov ...201323427274
simian virus 40 infection in the spinal cord of simian immunodeficiency virus-immunosuppressed rhesus macaques.progressive multifocal leukoencephalopathy (pml) is an often-fatal demyelinating disease of the cns that usually develops in immunocompromised individuals because of reactivation of quiescent jc virus (jcv). there are only a few reports of jcv infection in the human spinal cord. progressive multifocal leukoencephalopathy-like demyelinating lesions have been documented in the brains of simian immunodeficiency virus-infected macaques. to determine whether simian virus 40 (sv40) can infect and caus ...201526469249
genetic variation in vitro and in vivo of an attenuated lassa vaccine candidate.the attenuated lassa vaccine candidate ml29 is a laboratory-produced reassortant between lassa and mopeia viruses, two old world arenaviruses that differ by 40% in nucleic acid sequence. in our previous studies, ml29 elicited sterilizing immunity against lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (siv)-infected and uninfected rhesus macaques. here, we show that ml29 is stable after 12 passages in vitro withou ...201424335292
mesenchymoproliferative enteropathy associated with dual simian polyomavirus and rhesus cytomegalovirus infection in a simian immunodeficiency virus-infected rhesus macaque (macaca mulatta).opportunistic viral infections are common in simian immunodeficiency virus-infected rhesus macaques and include simian polyomavirus 40 (sv40), which causes interstitial nephritis, pneumonia, meningoencephalitis, and progressive multifocal leukoencephalopathy and rhesus cytomegalovirus (macacine herpesvirus-3), which is associated with many pathologic manifestations, including the formation of neutrophil-rich gastrointestinal masses. herein we report the findings of a simian immunodeficiency viru ...201323051916
high doses of gm-csf inhibit antibody responses in rectal secretions and diminish modified vaccinia ankara/simian immunodeficiency virus vaccine protection in trim5α-restrictive macaques.we tested, in rhesus macaques, the effects of a 500-fold range of an admixed recombinant modified vaccinia ankara (mva) expressing rhesus gm-csf (mva/gm-csf) on the immunogenicity and protection elicited by an mva/siv macaque 239 vaccine. high doses of mva/gm-csf did not affect the levels of systemic envelope (env)-specific ab, but it did decrease the expression of the gut-homing receptor α4β7 on plasmacytoid dendritic cells (p < 0.01) and the magnitudes of env-specific iga (p = 0.01) and igg (p ...201627683750
local control of repeated-dose rectal challenges in dna/mva-vaccinated macaques protected against a first series of simian immunodeficiency virus challenges.here, we report the results of a late boost and three additional series of simian immunodeficiency virus (siv) challenges in seven dna/modified vaccinia virus ankara (mva)-vaccinated rhesus macaques who resisted a first series of rectal challenges. during 29 additional challenges delivered over 2.3 years, all animals became infected. however, 13 blips of virus in six macaques and anamnestic env-specific rectal iga responses in three of the six suggested that local control of infections was occur ...201424574408
resistance to infection, early and persistent suppression of simian immunodeficiency virus sivmac251 viremia, and significant reduction of tissue viral burden after mucosal vaccination in female rhesus macaques.the efficacy of oral, intestinal, nasal, and vaginal vaccinations with dna simian immunodeficiency virus (siv)/interleukin-2 (il-2)/il-15, siv gag/pol/env recombinant modified vaccinia virus ankara (rmva), and at-2 sivmac239 inactivated particles was compared in rhesus macaques after low-dose vaginal challenge with sivmac251. intestinal immunization provided better protection from infection, as a significantly greater median number of challenges was necessary in this group than in the others. or ...201424155376
immunogenicity of a vaccine regimen composed of simian immunodeficiency virus dna, rmva, and viral particles administered to female rhesus macaques via four different mucosal routes.a comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (siv), interleukin 2 (il-2), and il-15 dnas, recombinant modified vaccinia virus ankara (rmva), and inactivated sivmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-siv immunity that may be critical to protection from siv infection and disease. a ...201323408627
lag3 expression in active mycobacterium tuberculosis infections.mycobacterium tuberculosis (mtb) is a highly successful pathogen because of its ability to persist in human lungs for long periods of time. mtb modulates several aspects of the host immune response. lymphocyte-activation gene 3 (lag3) is a protein with a high affinity for the cd4 receptor and is expressed mainly by regulatory t cells with immunomodulatory functions. to understand the function of lag3 during mtb infection, a nonhuman primate model of tuberculosis, which recapitulates key aspects ...201525549835
immunogenicity of repeated sendai viral vector vaccination in macaques.induction of durable cellular immune responses by vaccination is an important strategy for the control of persistent pathogen infection. viral vectors are promising vaccine tools for eliciting antigen-specific t-cell responses. repeated vaccination may contribute to durable memory t-cell induction, but anti-vector antibodies could be an obstacle to its efficacy. we previously developed a sendai virus (sev) vector vaccine and showed the potential of this vector for efficient t-cell induction in m ...201222884717
a method for obtaining simian immunodeficiency virus rna sequences from laser capture microdissected and immune captured cd68+ and cd163+ macrophages from frozen tissue sections of bone marrow and brain.laser capture microdissection (lcm) is used to extract cells or tissue regions for analysis of rna, dna or protein. several methods of lcm are established for different applications, but a protocol for consistently obtaining lentiviral rna from lcm captured immune cell populations is not described. obtaining optimal viral rna for analysis of viral genes from immune-captured cells using immunohistochemistry (ihc) and lcm is challenging. ihc protocols have long antibody incubation times that incre ...201728093272
altered regional homogeneity of brain spontaneous signals in siv infected rhesus macaque model.regional homogeneity (reho), a measurement from resting-state functional magnetic imaging (rs-fmri) to reflect local synchronization of brain activities, has been widely explored in previous studies of neurological diseases. siv infected model for detecting the neurological changes with progression was studied.201727989909
cabotegravir long acting injection protects macaques against intravenous challenge with sivmac251.we evaluated the effectiveness of cabotegravir (cab; gsk1265744 or gsk744) long acting as preexposure prophylaxis (prep) against intravenous simian immunodeficiency virus (siv) challenge in a model that mimics blood transfusions based on the per-act probability of infection.201727902508
evaluation of functional nk cell responses in vaccinated and siv-infected rhesus macaques.nk cells are crucial components of the innate immune system due to their capacity to exert rapid cytotoxic and immunomodulatory function in the absence of prior sensitization. nk cells can become activated by exposure to target cells and/or by cytokines produced by antigen-presenting cells. in this study, we examined the effects of a simian immunodeficiency virus (siv) vaccine regimen and subsequent siv infection on the cytotoxic and immunomodulatory functions of circulatory nk cells. while vacc ...201627630641
correction for rife et al., evolution of neuroadaptation in the periphery and purifying selection in the brain contribute to compartmentalization of simian immunodeficiency virus (siv) in the brains of rhesus macaques with siv-associated encephalitis. 201627620914
[effect of chinese herbal extract hna-1 on the thymic output function in simian immunodeficiency virus chronically infected chinese rhesus macaques].to observe the effect of chinese herbal extract hunan a-1 (hna-1) on the thymic output function in simian immunodeficiency virus (siv) chronically infected rhesus macaques.201627236896
increases in nkg2c expression on t cells and higher levels of circulating cd8(+) b cells are associated with sterilizing immunity provided by a live attenuated siv vaccine.vaccines based on live attenuated viruses are highly effective immunogens in the simian immunodeficiency virus (siv)/rhesus macaque animal model and offer the possibility of studying correlates of protection against infection with virulent virus. we utilized a tether system for studying, in naive macaques and animals vaccinated with a live-attenuated vaccine, the acute events after challenge with pathogenic siv. this approach allowed for the frequent sampling of small blood volumes without sedat ...201726986800
siv infection-mediated changes in gastrointestinal bacterial microbiome and virome are associated with immunodeficiency and prevented by vaccination.aids caused by simian immunodeficiency virus (siv) infection is associated with gastrointestinal disease, systemic immune activation, and, in cross-sectional studies, changes in the enteric virome. here we performed a longitudinal study of a vaccine cohort to define the natural history of changes in the fecal metagenome in siv-infected monkeys. matched rhesus macaques were either uninfected or intrarectally challenged with siv, with a subset receiving the ad26 vaccine, an adenovirus vector expre ...201626962943
simian immunodeficiency virus sivagm efficiently utilizes non-ccr5 entry pathways in african green monkey lymphocytes: potential role for gpr15 and cxcr6 as viral coreceptors.african green monkeys (agm) are natural hosts of simian immunodeficiency virus (siv), and infection in these animals is generally nonpathogenic, whereas infection of nonnatural hosts, such as rhesus macaques (rm), is commonly pathogenic. ccr5 has been described as the primary entry coreceptor for siv in vivo, while human-derived cxcr6 and gpr15 also appear to be used in vitro. however, sooty mangabeys that are genetically deficient in ccr5 due to an out-of-frame deletion are infectible with sivs ...201526656714
correction: decreased t follicular regulatory cell/t follicular helper cell (t(fh)) in simian immunodeficiency virus-infected rhesus macaques may contribute to accumulation of t(fh) in chronic infection. 201526637665
δ9-tetrahydrocannabinol (δ9-thc) promotes neuroimmune-modulatory microrna profile in striatum of simian immunodeficiency virus (siv)-infected macaques.cannabinoid administration before and after simian immunodeficiency virus (siv)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. δ9-tetrahydrocannabinol (δ9-thc) did not increase viral load in brain tissue or produce additive neuropsychological impairment in siv-infected macaques. to determine if the neuroimmunomodulation of δ9-thc involved differential microrna (mir) expression, mir expression in the striatum of uninfected macaques receiving vehicl ...201626607731
myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation.to define the cellular mechanisms of up-regulated inflammatory gene expression and down-regulated antiviral response in people experiencing perceived social isolation (loneliness), we conducted integrative analyses of leukocyte gene regulation in humans and rhesus macaques. five longitudinal leukocyte transcriptome surveys in 141 older adults showed up-regulation of the sympathetic nervous system (sns), monocyte population expansion, and up-regulation of the leukocyte conserved transcriptional r ...201526598672
the genome of the vervet (chlorocebus aethiops sabaeus).we describe a genome reference of the african green monkey or vervet (chlorocebus aethiops). this member of the old world monkey (owm) superfamily is uniquely valuable for genetic investigations of simian immunodeficiency virus (siv), for which it is the most abundant natural host species, and of a wide range of health-related phenotypes assessed in caribbean vervets (c. a. sabaeus), whose numbers have expanded dramatically since europeans introduced small numbers of their ancestors from west af ...201526377836
suppression of a natural killer cell response by simian immunodeficiency virus peptides.natural killer (nk) cell responses in primates are regulated in part through interactions between two highly polymorphic molecules, the killer-cell immunoglobulin-like receptors (kirs) on nk cells and their major histocompatibility complex (mhc) class i ligands on target cells. we previously reported that the binding of a common mhc class i molecule in the rhesus macaque, mamu-a1*002, to the inhibitory receptor mamu-kir3dl05 is stabilized by certain simian immunodeficiency virus (siv) peptides, ...201526333068
mir-21 in extracellular vesicles leads to neurotoxicity via tlr7 signaling in siv neurological disease.recent studies have found that extracellular vesicles (evs) play an important role in normal and disease processes. in the present study, we isolated and characterized evs from the brains of rhesus macaques, both with and without simian immunodeficiency virus (siv) induced central nervous system (cns) disease. small rna sequencing revealed increased mir-21 levels in evs from siv encephalitic (sive) brains. in situ hybridization revealed increased mir-21 expression in neurons and macrophage/micro ...201526154133
short communication: comparative evaluation of coformulated injectable combination antiretroviral therapy regimens in simian immunodeficiency virus-infected rhesus macaques.the use of nonhuman primate (nhp) models to study persistent residual virus and viral eradication strategies in combination antiretroviral therapy (cart)-treated individuals requires regimens that effectively suppress siv replication to clinically relevant levels in macaques. we developed and evaluated two novel cart regimens in sivmac239-infected rhesus macaques: (1) a "triple regimen" containing the nucleo(s/t)ide reverse transcriptase inhibitors emtricitabine (ftc) and tenofovir disoproxil fu ...201626150024
dualtropic cxcr6/ccr5 simian immunodeficiency virus (siv) infection of sooty mangabey primary lymphocytes: distinct coreceptor use in natural versus pathogenic hosts of siv.natural-host sooty mangabeys (sm) infected with simian immunodeficiency virus (siv) exhibit high viral loads but do not develop disease, whereas infection of rhesus macaques (rm) causes cd4(+) t cell loss and aids. several mechanisms have been proposed to explain these divergent outcomes, including differences in cell targeting, which have been linked to low expression of the canonical siv entry receptor ccr5 on cd4(+) t cells of sm and other natural hosts. we previously showed that infection an ...201526109719
simian immunodeficiency virus sivsab infection of rhesus macaques as a model of complete immunological suppression with persistent reservoirs of replication-competent virus: implications for cure research.simian immunodeficiency virus sivsab infection is completely controlled in rhesus macaques (rms) through functional immune responses. we report that in sivsab-infected rms, (i) viral replication is controlled to <0 to 3 copies/ml, (ii) about one-third of the virus strains in reservoirs are replication incompetent, and (iii) rebounding virus after cd8(+) cell depletion is replication competent and genetically similar to the original virus stock, suggesting early reservoir seeding. this model perm ...201525833043
immunophenotype of simian immunodeficiency virus-infected cells in the spleen of a rhesus monkey. 201525760311
ethanol impairs mucosal immunity against streptococcus pneumoniae infection by disrupting interleukin 17 gene expression.acute ethanol intoxication suppresses the host immune responses against streptococcus pneumoniae. as interleukin 17 (il-17) is a critical cytokine in host defense against extracellular pathogens, including s. pneumoniae, we hypothesized that ethanol impairs mucosal immunity against this pathogen by disrupting il-17 production or il-17 receptor (il-17r) signaling. a chronic ethanol feeding model in simian immunodeficiency virus (siv)-infected rhesus macaques and acute ethanol intoxication in a mu ...201525754201
up-regulation of tim-3 on t cells during acute simian immunodeficiency virus infection and on antigen specific responders.understanding the role of t-cell immunoglobulin and mucin domain-containing molecule 3 (tim-3) on t cells and dendritic cells during the course of simian immunodeficiency virus (siv) infection.201525715103
therapeutic envelope vaccination in combination with antiretroviral therapy temporarily rescues siv-specific cd4⁺ t-cell-dependent natural killer cell effector responses in chronically infected rhesus macaques.natural killer (nk) cells are essential components of the immune system, and due to their rapid response potential, can have a great impact during early anti-viral immune responses. we have previously shown that interleukin-2-dependent nk and cd4(+) t-cell co-operative immune responses exist in long-term simian immunodeficiency virus (siv) -infected controlling macaques and can be rescued in siv-infected non-controlling macaques by a short course of antiretroviral therapy (art). given that co-op ...201525626488
antigenic requirement for gag in a vaccine that protects against high-dose mucosal challenge with simian immunodeficiency virus.we reported previously on a vaccine approach that conferred apparent sterilizing immunity to sivsme660. the vaccine regimen employed a prime-boost using vectors based on recombinant vesicular stomatitis virus (vsv) and an alphavirus replicon expressing either siv gag or siv env. in the current study, we tested the ability of vectors expressing only the sivsme660 env protein to protect macaques against the same high-dose mucosal challenge. animals developed neutralizing antibody levels comparable ...201525591175
full genome sequence analysis of a novel adenovirus of rhesus macaque origin indicates a new simian adenovirus type and species.multiple novel simian adenoviruses have been isolated over the past years and their potential to cross the species barrier and infect the human population is an ever present threat. here we describe the isolation and full genome sequencing of a novel simian adenovirus (sadv) isolated from the urine of two independent, never co-housed, late stage simian immunodeficiency virus (siv)-infected rhesus macaques. the viral genome sequences revealed a novel type with a unique genome length, gc content, ...201425530944
bone marrow-imprinted gut-homing of plasmacytoid dendritic cells (pdcs) in acute simian immunodeficiency virus infection results in massive accumulation of hyperfunctional cd4+ pdcs in the mucosae.plasmacytoid dendritic cells (pdcs), a primary source of interferon α (ifn-α), provide a first line of innate immune defense against human immunodeficiency virus infection. however, their kinetics and functions during acute infection are poorly understood. in mucosal tissues of normal rhesus macaques, we found cd4(+) pdcs to be the subset responsible for most ifn-α and tumor necrosis factor α (tnf-α) production in response to toll-like receptor (tlr) 7/8 stimulation, compared with relatively ane ...201525489000
chronic binge alcohol administration accentuates expression of pro-fibrotic and inflammatory genes in the skeletal muscle of simian immunodeficiency virus-infected macaques.chronic binge alcohol (cba) administration exacerbates skeletal muscle (skm) wasting at the terminal stage of simian immunodeficiency virus (siv) infection in rhesus macaques. this is associated with a pro-inflammatory and oxidative milieu which we have previously shown to be associated with a disrupted balance between anabolic and catabolic mechanisms. in this study, we attempted to characterize the skm gene expression signature in cba-administered siv-infected macaques, using the same animals ...201425421506
multiple low-dose challenges in a rhesus macaque aids vaccine trial result in an evolving host response that affects protective outcome.using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque aids vaccine trial. samples were collected from animals prior to and after vaccination with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-ig loaded with simian immunodeficiency virus (siv) peptides, either alone or in combination with a siv-gp120 protein boost. additional samples were collected following multip ...201425274805
dysregulation of myelopoiesis by chronic alcohol administration during early siv infection of rhesus macaques.chronic alcohol intoxication suppresses immune function and increases osteoporosis risk suggesting bone-tissue cytotoxicity. human immunodeficiency virus infection leads to similar impairments. this study investigated the effects of chronic alcohol administration during the early stage of simian immunodeficiency virus (siv) infection on hematopoietic stem and progenitor cells (hspcs) and their differentiated progeny in the bone marrow and peripheral blood of rhesus macaques.201424942272
host factors determine differential disease progression after infection with nef-deleted simian immunodeficiency virus.infection of macaques with live attenuated simian immunodeficiency virus (siv) usually results in long-lasting efficient protection against infection with pathogenic immunodeficiency viruses. however, attenuation by deletion of regulatory genes such as nef is not complete, leading to a high viral load and fatal disease in some animals. to characterize immunological parameters and polymorphic host factors, we studied 17 rhesus macaques infected with attenuated sivmac239δnu. eight animals were abl ...201424928910
divergent cd4+ t memory stem cell dynamics in pathogenic and nonpathogenic simian immunodeficiency virus infections.recent studies have identified a subset of memory t cells with stem cell-like properties (t(scm)) that include increased longevity and proliferative potential. in this study, we examined the dynamics of cd4(+) t(scm) during pathogenic siv infection of rhesus macaques (rm) and nonpathogenic siv infection of sooty mangabeys (sm). whereas siv-infected rm show selective numeric preservation of cd4(+) t(scm), siv infection induced a complex perturbation of these cells defined by depletion of cd4(+)cc ...201424729621
pathogenic features associated with increased virulence upon simian immunodeficiency virus cross-species transmission from natural hosts.while simian immunodeficiency viruses (sivs) are generally nonpathogenic in their natural hosts, dramatic increases in pathogenicity may occur upon cross-species transmission to new hosts. deciphering the drivers of these increases in virulence is of major interest for understanding the emergence of new human immunodeficiency viruses (hivs). we transmitted sivsab from the sabaeus species of african green monkeys (agms) to pigtailed macaques (ptms). high acute viral replication occurred in all si ...201424696477
chronic binge alcohol consumption alters myogenic gene expression and reduces in vitro myogenic differentiation potential of myoblasts from rhesus macaques.chronic alcohol abuse is associated with skeletal muscle myopathy. previously, we demonstrated that chronic binge alcohol (cba) consumption by rhesus macaques accentuates skeletal muscle wasting at end-stage of simian immunodeficiency virus (siv) infection. a proinflammatory, prooxidative milieu and enhanced ubiquitin proteasome activity were identified as possible mechanisms leading to loss of skeletal muscle. the possibility that impaired regenerative capacity, as reflected by the ability of m ...201424671243
pas-positive extracellular deposits within germinal centers of hyperplastic follicles during siv infection in a rhesus macaque.lymphoid tissue remodeling is characteristic of chronic simian immunodeficiency virus infection.201424628065
siv vpx is essential for macrophage infection but not for development of aids.analysis of rhesus macaques infected with a vpx deletion mutant virus of simian immunodeficiency virus mac239 (sivδvpx) demonstrates that vpx is essential for efficient monocyte/macrophage infection in vivo but is not necessary for development of aids. to compare myeloid-lineage cell infection in monkeys infected with sivδvpx compared to sivmac239, we analyzed lymphoid and gastrointestinal tissues from sivδvpx-infected rhesus (n = 5), sivmac239-infected rhesus with siv encephalitis (7 siv239e), ...201424465411
hematology and serum chemistry values of sooty mangabeys (cercocebus atys): comparison with rhesus monkeys.the sooty mangabey is a vulnerable west african species that naturally harbors simian immunodeficiency virus (siv) without pathological symptoms. we present normative hematology and serum chemistry values for this species.201424256341
[experimental observation of sivmac239 chinese rhesus monkey model at sub-acute phase of aids].to observe t lymphocyte subsets and indicators of changes in viral load in sub-acute period in chinese rhesus monkey model of aids sivmac239. to explore virology related index variation in sub-acute period of the chinese rhesus monkey model of aids.201324228536
serial cervicovaginal exposures with replication-deficient sivsm induce higher dendritic cell (pdc) and cd4+ t-cell infiltrates not associated with prevention but a more severe sivmac251 infection of rhesus macaques.intravaginal exposure to simian immunodeficiency virus (siv) acutely recruits interferon-alpha (ifn-α) producing plasmacytoid dendritic cells (pdc) and cd4 t-lymphocyte targets to the endocervix of nonhuman primates. we tested the impact of repeated cervicovaginal exposures to noninfectious, defective siv particles over 72 hours on a subsequent cervicovaginal challenge with replication competent siv.201424226059
control of simian immunodeficiency virus replication by vaccine-induced gag- and vif-specific cd8+ t cells.for development of an effective t cell-based aids vaccine, it is critical to define the antigens that elicit the most potent responses. recent studies have suggested that gag-specific and possibly vif/nef-specific cd8(+) t cells can be important in control of the aids virus. here, we tested whether induction of these cd8(+) t cells by prophylactic vaccination can result in control of simian immunodeficiency virus (siv) replication in burmese rhesus macaques sharing the major histocompatibility c ...201424155398
tetherin upregulation in simian immunodeficiency virus-infected macaques.here we show that simian immunodeficiency virus (siv) infection of rhesus macaques results in rapid upregulation of tetherin (bst-2 or cd317) on peripheral blood lymphocytes, including the cd4(+) ccr5(+) t cell targets of virus infection, with a peak of induction that coincides with peak alpha interferon (ifn-α) levels in plasma, and that tetherin remains above baseline levels throughout chronic infection. these observations are consistent with a role for tetherin in innate immunity to immunodef ...201324109219
safety and tolerability of a live oral salmonella typhimurium vaccine candidate in siv-infected nonhuman primates.nontyphoidal salmonella (nts) serovars are a common cause of acute food-borne gastroenteritis worldwide and can cause invasive systemic disease in young infants, the elderly, and immunocompromised hosts, accompanied by high case fatality. vaccination against invasive nts disease is warranted where the disease incidence and mortality are high and multidrug resistance is prevalent, as in sub-saharan africa. live-attenuated vaccines that mimic natural infection constitute one strategy to elicit pro ...201324099872
live attenuated rev-independent nef¯siv enhances acquisition of heterologous sivsme660 in acutely vaccinated rhesus macaques.rhesus macaques (rms) inoculated with live-attenuated rev-independent nef¯ simian immunodeficiency virus (rev-ind nef¯siv) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. we tested the capacity of this live-attenuated virus to protect rms against pathogenic, heterologous sivsme660 challenges.201324098702
longitudinal analysis of intra-host simian immunodeficiency virus recombination in varied tissues of the rhesus macaque model for neuroaids.human immunodeficiency virus intra-host recombination has never been studied in vivo both during early infection and throughout disease progression. the cd8-depleted rhesus macaque model of neuroaids was used to investigate the impact of recombination from early infection up to the onset of neuropathology in animals inoculated with a simian immunodeficiency virus (siv) swarm. several lymphoid and non-lymphoid tissues were collected longitudinally at 21 days post-infection (p.i.), 61 days p.i. an ...201323963535
immunological and virological analyses of rhesus macaques immunized with chimpanzee adenoviruses expressing the simian immunodeficiency virus gag/tat fusion protein and challenged intrarectally with repeated low doses of sivmac.human adenovirus (adhu)-based candidate aids vaccine can provide protection from simian immunodeficiency virus (siv) transmission and disease progression. however, their potential use may be limited by widespread preexisting immunity to the vector. in contrast, preexisting immunity to chimpanzee adenoviruses (adc) is relatively rare. in this study, we utilized two regimens of prime-boost immunizations with adc serotype sad-v23 (also called adc6) and sad-v24 (also called adc7) expressing siv gag/ ...201323804645
macaque paneth cells express lymphoid chemokine cxcl13 and other antimicrobial peptides not previously described as expressed in intestinal crypts.cxcl13 is a constitutively expressed chemokine that controls migration of immune cells to lymphoid follicles. previously, we found cxcl13 mrna levels increased in rhesus macaque spleen tissues during aids. this led us to examine the levels and locations of cxcl13 by detailed in situ methods in cynomolgus macaque lymphoid and intestinal tissues. our results revealed that there were distinct localization patterns of cxcl13 mrna compared to protein in germinal centers. these patterns shifted during ...201323803902
effects of alcohol consumption on antigen-specific cellular and humoral immune responses to siv in rhesus macaques.simian immunodeficiency virus (siv) infection in macaques chronically receiving ethanol results in significantly higher plasma viral loads and more rapid progression to end-stage disease. we thus hypothesized that the increased plasma viral load in ethanol-treated, siv-infected macaques would negatively correlate with antigen-specific immune responses.201323799411
crystallization and preliminary x-ray crystallographic analysis of the rhesus macaque mhc class i molecule mamu-b*17 complexed with an immunodominant sivmac239 env epitope.long-term nonprogression during simian immunodeficiency virus (siv) infection has been strongly associated with the major histocompatibility complex (mhc) class i allele mamu-b*17. here, a complex of rhesus macaque mamu-b*17 with rhesus macaque β2-microglobulin (β2m) and an immunodominant peptide (sivmac239 env241-251; lrcndtnysgf; env lf11) derived from the siv env protein was crystallized by the hanging-drop method using peg 3350 as a precipitating agent. the crystals belonged to the primitive ...201323722842
gain-of-sensitivity mutations in a trim5-resistant primary isolate of pathogenic siv identify two independent conserved determinants of trim5α specificity.retroviral capsid recognition by trim5 blocks productive infection. rhesus macaques harbor three functionally distinct trim5 alleles: trim5α(q) , trim5α(tfp) and trim5(cypa) . despite the high degree of amino acid identity between trim5α(q) and trim5α(tfp) alleles, the q/tfp polymorphism results in the differential restriction of some primate lentiviruses, suggesting these alleles differ in how they engage these capsids. simian immunodeficiency virus of rhesus macaques (sivmac) evolved to resist ...201323675300
influence of mismatch of env sequences on vaccine protection by live attenuated simian immunodeficiency virus.vaccine/challenge experiments that utilize live attenuated strains of simian immunodeficiency virus (siv) in monkeys may be useful for elucidating what is needed from a vaccine in order to achieve protective immunity. derivatives of sivmac239 and sivmac239δnef were constructed in which env sequences were replaced with those of the heterologous strain e543; these were then used in vaccine/challenge experiments. when challenge occurred at 22 weeks, 10 of 12 monkeys exhibited apparent sterilizing i ...201323637396
no viral evolution in the lymph nodes of simian immunodeficiency virus-infected rhesus macaques during combined antiretroviral therapy.to elucidate the mode of viral persistence in primate lentivirus-infected individuals during combination antiretroviral therapy (cart), four simian immunodeficiency virus 239-infected monkeys were treated with cart for 1 year. the viral env genes prepared from total rna extracted from the mesenteric lymph nodes collected at the completion of therapy were assessed by single genome amplification. analyses of nucleotide substitutions and phylogeny revealed no viral evolution during cart.201323408611
molecular requirements for t cell recognition of n-myristoylated peptides derived from the simian immunodeficiency virus nef protein.we have recently isolated a rhesus macaque cytotoxic t cell line, 2n5.1, that specifically recognizes an n-myristoylated 5-mer peptide (c(14)-gly-gly-ala-ile-ser [c14nef5]) derived from the simian immunodeficiency virus (siv) nef protein. such c14nef5-specific t cells expand in the circulation of siv-infected monkeys, underscoring the capacity of t cells to recognize viral lipopeptides; however, the molecular basis for the lipopeptide antigen presentation remains to be elucidated. here, function ...201323097434
activating kir copy number variation is associated with granzyme b release by nk cells during primary simian immunodeficiency virus infection in rhesus monkeys.here we show that the number of activating killer cell immunoglobulin-like receptor (kir) copies in rhesus monkeys is associated with the extent of release of cytotoxic granules by cytolytic nk cells during primary simian immunodeficiency virus sivmac251 infection. these findings suggest that nk cells expressing high levels of activating kirs efficiently kill sivmac251-infected cells, and this efficient killing contributes to the nk cell-mediated control of replication of this virus during early ...201223015705
expression sequence tag library derived from peripheral blood mononuclear cells of the chlorocebus sabaeus.african green monkeys (agm) are amongst the most frequently used nonhuman primate models in clinical and biomedical research, nevertheless only few genomic resources exist for this species. such information would be essential for the development of dedicated new generation technologies in fundamental and pre-clinical research using this model, and would deliver new insights into primate evolution.201222726727
immunogenicity of dna vaccines encoding simian immunodeficiency virus antigen targeted to dendritic cells in rhesus macaques.targeting antigens encoded by dna vaccines to dendritic cells (dcs) in the presence of adjuvants enhances their immunogenicity and efficacy in mice.201222720025
viral vectored granulocyte-macrophage colony stimulating factor inhibits vaccine protection in an siv challenge model: protection correlates with neutralizing antibody.in a previous vaccine study, we reported significant and apparently sterilizing immunity to high-dose, mucosal, simian immunodeficiency virus (siv) quasi-species challenge. the vaccine consisted of vectors based on vesicular stomatitis virus (vsv) expressing simian immunodeficiency virus (siv) gag and env genes, a boost with propagating replicon particles expressing the same siv genes, and a second boost with vsv-based vectors. concurrent with that published study we had a parallel group of maca ...201222537983
association of major histocompatibility complex class i haplotypes with disease progression after simian immunodeficiency virus challenge in burmese rhesus macaques.nonhuman primate aids models are essential for the analysis of aids pathogenesis and the evaluation of vaccine efficacy. multiple studies on human immunodeficiency virus and simian immunodeficiency virus (siv) infection have indicated the association of major histocompatibility complex class i (mhc-i) genotypes with rapid or slow aids progression. the accumulation of macaque groups that share not only a single mhc-i allele but also an mhc-i haplotype consisting of multiple polymorphic mhc-i loci ...201222491464
efficient transmission and persistence of low-frequency sivmac251 variants in cd8-depleted rhesus macaques with different neuropathology.infection of cd8-depleted rhesus macaques with the genetically heterogeneous simian immunodeficiency virus (siv)mac251 viral swarm provides a rapid-disease model for simian acquired immune deficiency syndrome and siv-encephalitis (sive). the objective was to evaluate how the diversity of the swarm influences the initial seeding of the infection that may potentially affect disease progression. plasma, lymphoid and non-lymphoid (brain and lung) tissues were collected from two infected macaques eut ...201222302881
nonmyeloablative conditioning regimen to increase engraftment of gene-modified hematopoietic stem cells in young rhesus monkeys.immune responses to transgene products may lead to rejection of transduced cells, limiting successful gene therapy for genetic diseases. while moderate dosages of chemotherapeutic agents such as busulfan may increase hematopoietic stem cells (hsc) engraftment, they are not immune suppressive and do not abrogate immune responses to transgene products. studies focused on nonmyeloablative conditioning with busulfan ± fludarabine in a clinically relevant monkey model to induce immune suppression to ...201222294147
siv infection of macaques: a model for studying aids and drug abuse.rhesus monkeys (macaca mulatta) and the simian immunodeficiency virus (siv) were used as an animal model system to evaluate longitudinally the effects of opioid dependence on the development of aids. results have shown that in addition to weakening the host's t cell and pmn functions, chronic opioid treatment of sivmac239-infected animals caused (a) an increased virus replication rate, (b) an increased rate of viral mutation, (c) a nascent humoral (antibody) response against mutated autologous s ...199726735947
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