Publications

the presence of protective cytotoxic t lymphocytes does not correlate with shorter lifespans of productively infected cells in hiv-1 infection.	cd8+ cytotoxic t lymphocytes (ctl) are important in the control of hiv infection. although ctl are thought to reduce the lifespan of productively infected cells, cd8+ t-cell depletion in simian immunodeficiency virus-infected rhesus-macaques showed no effect on the lifespan of productively infected cells. as cd8+ t-cell responses that successfully delay hiv disease progression occur only in a minority of hiv-infected individuals, we studied the hypothesis that the ability of ctl to reduce the li ...	2016	26731751
translocation of microbes and changes of immunocytes in the gut of rapid- and slow-progressor chinese rhesus macaques infected with sivmac239.	human/simian immunodeficiency virus (hiv/siv) infection can cause severe depletion of cd4(+) t cells in both plasma and mucosa; it also results in damage to the gut mucosa barrier, which makes the condition more conducive to microbial translocation. in this study, we used siv-infected chinese rhesus macaques to quantify the extent of microbial translocation and the function of immune cells in the entire gastrointestinal tract and to compare their differences between rapid and slow progressors. t ...	2016	26725773
elevated plasma viral loads in romidepsin-treated simian immunodeficiency virus-infected rhesus macaques on suppressive combination antiretroviral therapy.	replication-competent human immunodeficiency virus (hiv) persists in infected people despite suppressive combination antiretroviral therapy (cart), and it represents a major obstacle to hiv functional cure or eradication. we have developed a model of cart-mediated viral suppression in simian human immunodeficiency virus (siv) mac239-infected indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (hdaci) romidepsin (rmd) on viremia in vivo. eight macaques virological ...	2015	26711758
chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques.	there are more than 1 million persons living with hiv/aids (plwha) in the united states and approximately 40 % of them have a history of alcohol use disorders (aud). chronic heavy alcohol consumption and hiv/aids both result in reduced lean body mass and muscle dysfunction, increasing the incidence of comorbid conditions. previous studies from our laboratory using rhesus macaques infected with simian immunodeficiency virus (siv) demonstrated that chronic binge alcohol (cba) administration in the ...	2015	26699868
loss of intraepidermal nerve fiber density during siv peripheral neuropathy is mediated by monocyte activation and elevated monocyte chemotactic proteins.	peripheral neuropathy (pn) continues to be a major complication of human immunodeficiency virus (hiv) infection despite successful anti-retroviral therapy. human hiv-pn can be recapitulated in a cd8-depleted, simian immunodeficiency virus (siv)-infected rhesus macaque animal model, characterized by a loss of intraepidermal nerve fiber density (ienfd) and damage to the dorsal root ganglia (drg). increased monocyte traffic to the drg has previously been associated with severe drg pathology, as wel ...	2015	26683323
signatures in simian immunodeficiency virus sivsme660 envelope gp120 are associated with mucosal transmission but not vaccination breakthrough in rhesus macaques.	mucosal surfaces are vulnerable to human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) infection and thus are key sites for eliciting vaccine-mediated protection. vaccine protocols carried out at the yerkes primate research center utilized sivmac239-based immunization strategies with intrarectal and intravaginal sivsme660 challenge of rhesus macaques. we investigated whether there were genetic signatures associated with sivsme660 intrarectal and intravaginal transmissions in v ...	2015	26676777
siv/shiv infection triggers vascular inflammation, diminished expression of krüppel-like factor 2 and endothelial dysfunction.	human immunodeficiency virus (hiv) infection is associated with increased risk of thromboembolic and cardiovascular comorbid conditions. although systemic inflammation is linked to cardiovascular risk, direct evidence of vascular inflammation and endothelial dysfunction is lacking.	2016	26671887
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 ...	2015	26656714
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.		2015	26637665
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 ...	2016	26607731
chronic alcohol increases cd8+ t-cell immunosenescence in simian immunodeficiency virus-infected rhesus macaques.	activated cd8+ t-cells correlate with viral load and may foretell antiretroviral therapy (art) failure. hiv infection has been suggested to accelerate immunosenescence through chronic persistent inflammation. alcohol-use disorders (aud) are prevalent in persons living with hiv/aids (plwha). we tested the hypothesis that hazardous alcohol consumption accelerates immune activation and immunosenescence. immune activation and immunosenescence were examined in cd8+ t lymphocytes (cd3+cd4-cd8+) isolat ...	2015	26603633
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 ...	2015	26598672
gut-resident lactobacillus abundance associates with ido1 inhibition and th17 dynamics in siv-infected macaques.	gut microbes can profoundly modulate mucosal barrier-promoting th17 cells in mammals. a salient feature of hiv/simian immunodeficiency virus (siv) immunopathogenesis is the loss of th17 cells, which has been linked to increased activity of the immunomodulatory enzyme, indoleamine 2,3-dioxygenase 1 (ido 1). the role of gut microbes in this system remains unknown, and the siv-infected rhesus macaque provides a well-described model for hiv-associated th17 loss and mucosal immune disruption. we obse ...	2015	26586432
next-generation mrna sequencing reveals pyroptosis-induced cd4+ t cell death in early simian immunodeficiency virus-infected lymphoid tissues.	lymphoid tissues (lts) are the principal sites where human immunodeficiency virus type 1 (hiv-1) replicates and virus-host interactions take place, resulting in immunopathology in the form of inflammation, immune activation, and cd4(+) t cell death. the hiv-1 pathogenesis in lts has been extensively studied; however, our understanding of the virus-host interactions in the very early stages of infection remains incomplete. we investigated virus-host interactions in the rectal draining lymph nodes ...	2015	26559826
increased bst2 expression during simian immunodeficiency virus infection is not a determinant of disease progression in rhesus monkeys.	bone marrow stromal cell antigen 2 (bst2), also known as tetherin, hm1.24 or cd317 represents a type 2 integral membrane protein, which has been described to restrict the production of some enveloped viruses by inhibiting the virus release from the cell surface. this innate antiviral mechanism is counteracted by the hiv-1 viral factor vpu, targeting bst2 for cellular degradation. since antiviral bst2 activity has been mainly confirmed by in vitro data, we investigated its role in vivo on the dis ...	2015	26554913
noncytolytic cd8+ cell mediated antiviral response represents a strong element in the immune response of simian immunodeficiency virus-infected long-term non-progressing rhesus macaques.	the ability of long term non progressors to maintain very low levels of hiv/siv and a healthy state, involves various host genetic and immunological factors. cd8+ non-cytolytic antiviral response (cnar) most likely plays an important role in this regard. in order to gain a deeper insight into this unique phenomenon, the ability of cd8+ t cells to suppress viral replication in vitro was investigated in 16 uninfected, longitudinally in 23 siv-infected long-term non-progressing (ltnps), and 10 siv- ...	2015	26551355
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 ...	2015	26469249
host anti-antibody responses following adeno-associated virus-mediated delivery of antibodies against hiv and siv in rhesus monkeys.	long-term delivery of antibodies against the human immunodeficiency virus (hiv) using adeno-associated virus (aav) vectors is a promising approach for the prevention or treatment of hiv infection. however, host antibody responses to the delivered antibody are a serious concern that could significantly limit the applicability of this approach. here, we describe the dynamics and characteristics of the anti-antibody responses in monkeys that received either rhesus anti-simian immunodeficiency virus ...	2016	26444083
longitudinal assessment of fractional anisotropy alterations caused by simian immunodeficiency virus infection: a preliminary diffusion tensor imaging study.	previous diffusion tensor imaging (dti) studies found that human immunodeficiency virus (hiv) infection led to white matter (wm) microstructure degeneration. most of the dti studies were cross-sectional and thus merely investigated only one specific point in the disease. in order to systematically study the wm impairments caused by hiv infection, more longitudinal studies are needed. however, longitudinal studies on hiv patients are very difficult to conduct. to address this question, we employe ...	2016	26438160
preferential destruction of interstitial macrophages over alveolar macrophages as a cause of pulmonary disease in simian immunodeficiency virus-infected rhesus macaques.	to our knowledge, this study demonstrates for the first time that the aids virus differentially impacts two distinct subsets of lung macrophages. the predominant macrophages harvested by bronchoalveolar lavage (bal), alveolar macrophages (ams), are routinely used in studies on human lung macrophages, are long-lived cells, and exhibit low turnover. interstitial macrophages (ims) inhabit the lung tissue, are not recovered with bal, are shorter-lived, and exhibit higher baseline turnover rates dist ...	2015	26432896
persistent simian immunodeficiency virus infection causes ultimate depletion of follicular th cells in aids.	cd4(+) t follicular helper (tfh) cells are critical for the generation of humoral immune responses to pathogenic infections, providing help for b cell development, survival, and affinity maturation of abs. although cd4(+) tfh cells are reported to accumulate in hiv or siv infection, we found that germinal center tfh cells, defined in this study as cxcr5(+)pd-1(high)cd4(+) t cells, did not consistently accumulate in chronically siv-infected rhesus macaques compared with those infected with less p ...	2015	26408660
characterization of the drug resistance profiles of integrase strand transfer inhibitors in simian immunodeficiency virus sivmac239.	we previously showed that the simian immunodeficiency virus sivmac239 is susceptible to human immunodeficiency virus (hiv) integrase (in) strand transfer inhibitors (instis) and that the same in drug resistance mutations result in similar phenotypes in both viruses. now we wished to determine whether tissue culture drug selection studies with siv would yield the same resistance mutations as in hiv. tissue culture selection experiments were performed using rhesus macaque peripheral blood mononucl ...	2015	26378179
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 ...	2015	26377836
gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic siv infection.	hiv targets the gut mucosa early in infection, causing immune and epithelial barrier dysfunction and disease progression. however, gut mucosal sensing and innate immune signaling through mucosal pattern recognition receptors (prrs) during hiv infection and disease progression are not well defined. using the simian immunodeficiency virus (siv)-infected rhesus macaque model of aids, we found a robust increase in prrs and inflammatory cytokine gene expression during the acute siv infection in both ...	2016	26376368
exclusive decoration of simian immunodeficiency virus env with high-mannose type n-glycans is not compatible with mucosal transmission in rhesus macaques.	human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) envelope (env) proteins are extensively decorated with n-glycans, predominantly of the high-mannose type. however, it is unclear how high-mannose n-glycans on env impact viral spread. we show that exclusive modification of siv env with these n-glycans reduces viral infectivity and abrogates mucosal transmission, despite increasing viral capture by immune cell lectins. thus, high-mannose n-glycans have opposed effects on s ...	2015	26355090
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, ...	2015	26333068
transcription profiling of cd4⁺ t cells in rhesus macaques that infected with simian-human immunodeficiency virus and re-challenged with sivmac251.	insights into the host factors that contribute to an effective antiviral immune response may be obtained by examining global gene expression in simian-human immunodeficiency virus (shiv)-infected non-human primates that exhibit different virological outcomes.	2015	26332118
decreased t follicular regulatory cell/t follicular helper cell (tfh) in simian immunodeficiency virus-infected rhesus macaques may contribute to accumulation of tfh in chronic infection.	t follicular helper cells (tfh) are critical for the development and maintenance of germinal center (gc) and humoral immune responses. during chronic hiv/siv infection, tfh accumulate, possibly as a result of ag persistence. the hiv/siv-associated tfh expansion may also reflect lack of regulation by suppressive follicular regulatory cd4(+) t cells (tfr). tfr are natural regulatory t cells (treg) that migrate into the follicle and, similar to tfh, upregulate cxcr5, bcl-6, and pd1. in this study, ...	2015	26297764
macrophages and myeloid dendritic cells lose t cell-stimulating function in simian immunodeficiency virus infection associated with diminished il-12 and ifn-α production.	impaired t cell responses are a defining characteristic of hiv infection, but the extent to which altered mononuclear phagocyte function contributes to this defect is unclear. we show that mononuclear phagocytes enriched from rhesus macaque lymph nodes have suppressed ability to stimulate cd4 t cell proliferation and ifn-γ release after acute siv infection. when individual populations were isolated, myeloid dendritic cells (mdc) and macrophages but not plasmacytoid dc (pdc) had suppressed capaci ...	2015	26297760
regulatory and helper follicular t cells and antibody avidity to simian immunodeficiency virus glycoprotein 120.	t follicular regulatory cells (tfr) are a suppressive cd4(+) t cell subset that migrates to germinal centers (gc) during ag presentation by upregulating the chemokine receptor cxcr5. in the gc, tfr control t follicular helper cell (tfh) expansion and modulate the development of high-affinity ag-specific responses. in this study, we identified and characterized tfr as cxcr5(+)ccr7(-) "follicular" t regulatory cells in lymphoid tissues of healthy rhesus macaques, and we studied their dynamics thro ...	2015	26297759
vaccine-induced simian immunodeficiency virus-specific cd8+ t-cell responses focused on a single nef epitope select for escape variants shortly after infection.	certain major histocompatibility complex class i (mhc-i) alleles (e.g., hla-b27) are enriched among human immunodeficiency virus type 1 (hiv-1)-infected individuals who suppress viremia without treatment (termed "elite controllers" [ecs]). likewise, mamu-b08 expression also predisposes rhesus macaques to control simian immunodeficiency virus (siv) replication. given the similarities between mamu-b08 and hla-b27, siv-infected mamu-b08(+) animals provide a model to investigate hla-b27-mediat ...	2015	26292326
exposure to siv in utero results in reduced viral loads and altered responsiveness to postnatal challenge.	hiv disease progression appears to be driven by increased immune activation. given observations that fetal exposure to infectious pathogens in utero can result in reduced immune responses, or tolerance, to those pathogens postnatally, we hypothesized that fetal exposure to hiv may render the fetus tolerant to the virus, thus reducing damage caused by immune activation during infection later in life. to test this hypothesis, fetal rhesus macaques (macaca mulatta) were injected with the attenuated ...	2015	26268312
breakthrough of siv strain sme660 challenge in siv strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses.	although the correlates of immunological protection from human immunodeficiency virus or simian immunodeficiency virus infection remain incompletely understood, it is generally believed that medium to high titers of serum neutralizing antibodies (nabs) against the challenge virus will prevent infection. this paradigm is based on a series of studies in which passive transfer of hiv-specific nabs protected rhesus macaques (rms) from subsequent mucosal challenge with a chimeric human/simian immunod ...	2015	26261312
elite control, gut cd4 t cell sparing, and enhanced mucosal t cell responses in macaca nemestrina infected by a simian immunodeficiency virus lacking a gp41 trafficking motif.	deletion of gly-720 and tyr-721 from a highly conserved gyxxø trafficking signal in the sivmac239 envelope glycoprotein cytoplasmic domain, producing a virus termed δgy, leads to a striking perturbation in pathogenesis in rhesus macaques (macaca mulatta). infected macaques develop immune activation and progress to aids, but with only limited and transient infection of intestinal cd4(+) t cells and an absence of microbial translocation. here we evaluated δgy in pig-tailed macaques (macaca nemestr ...	2015	26223646
reduced simian immunodeficiency virus replication in macrophages of sooty mangabeys is associated with increased expression of host restriction factors.	macrophages are target cells of hiv/siv infection that may play a role in aids pathogenesis and contribute to the long-lived reservoir of latently infected cells during antiretroviral therapy (art). in previous work, we and others have shown that during pathogenic siv infection of rhesus macaques (rms), rapid disease progression is associated with high levels of in vivo macrophage infection. in contrast, during nonpathogenic siv infection of sooty mangabeys (sms), neither spontaneous nor experim ...	2015	26202248
rhesus immune responses to siv gag expressed by recombinant bcg vectors are independent from pre-existing mycobacterial immunity.	a recombinant mycobacterium bovis bcg (rbcg) vector expressing hiv transgenes is an attractive candidate as a dual vaccine against hiv and tb. however, pre-existing immune responses to mycobacteria may influence immune responses to rbcg. we analyzed data from a rhesus rbcg trial to determine the effect of pre-existing mycobacterial immune responses on the vaccine-induced responses to the vector and expressed transgene.	2015	26192357
rapid development of gp120-focused neutralizing b cell responses during acute simian immunodeficiency virus infection of african green monkeys.	the initial phases of acute human immunodeficiency virus type 1 (hiv-1) infection may be critical for development of effective envelope (env)-specific antibodies capable of impeding the establishment of the latent pool of hiv-1-infected cd4(+) t cells, preventing virus-induced immune hyperactivation to limit disease progression and blocking vertical virus transmission. however, the initial systemic hiv-1 env-specific antibody response targets gp41 epitopes and fails to control acute-phase viremi ...	2015	26157116
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 ...	2015	26154133
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 ...	2016	26150024
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 ...	2015	26109719
high expression levels of blys/baff by blood dendritic cells and granulocytes are associated with b-cell dysregulation in siv-infected rhesus macaques.	dendritic cells (dcs) modulate b-cell survival and differentiation, mainly through production of growth factors such as b lymphocyte stimulator (blys/baff). in recent longitudinal studies involving hiv-1-infected individuals with different rates of disease progression, we have shown that dcs were altered in number and phenotype in the context of hiv-1 disease progression and b-cell dysregulations were associated with increased blys/baff expression in plasma and by blood myeloid dcs (mdcs) in rap ...	2015	26107380
cocrystal structures of antibody n60-i3 and antibody jr4 in complex with gp120 define more cluster a epitopes involved in effective antibody-dependent effector function against hiv-1.	accumulating evidence indicates a role for fc receptor (fcr)-mediated effector functions of antibodies, including antibody-dependent cell-mediated cytotoxicity (adcc), in prevention of human immunodeficiency virus type 1 (hiv-1) acquisition and in postinfection control of viremia. consequently, an understanding of the molecular basis for env epitopes that constitute effective adcc targets is of fundamental interest for humoral anti-hiv-1 immunity and for hiv-1 vaccine design. a substantial porti ...	2015	26085162
differential impact of in vivo cd8+ t lymphocyte depletion in controller versus progressor simian immunodeficiency virus-infected macaques.	numerous studies have demonstrated that cd8(+) t lymphocytes suppress virus replication during human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) infection. however, the mechanisms underlying this activity of t cells remain incompletely understood. here, we conducted cd8(+) t lymphocyte depletion in 15 rhesus macaques (rms) infected intravenously (i.v.) with sivmac239. at day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) w ...	2015	26063417
tracking the emergence of host-specific simian immunodeficiency virus env and nef populations reveals nef early adaptation and convergent evolution in brain of naturally progressing rhesus macaques.	while a clear understanding of the events leading to successful establishment of host-specific viral populations and productive infection in the central nervous system (cns) has not yet been reached, the simian immunodeficiency virus (siv)-infected rhesus macaque provides a powerful model for the study of human immunodeficiency virus (hiv) intrahost evolution and neuropathogenesis. the evolution of the gp120 and nef genes, which encode two key proteins required for the establishment and maintena ...	2015	26041280
high immune activation and abnormal expression of cytokines contribute to death of shiv89.6-infected chinese rhesus macaques.	chinese rhesus macaques (crms) are ideal experimental animals for studying the pathogenesis of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) and for vaccine research. shiv89.6 has been reported to be an attenuated virus because, in most cases, shiv89.6 infection only causes limited alteration of immune cells and tissues, and it has been used commonly for vaccine research. after two serial passages in vivo, shiv (shiv-89.6p) induces cd4 lymphopenia and an aids-like di ...	2015	26036562
characterization and implementation of a diverse simian immunodeficiency virus sivsm envelope panel in the assessment of neutralizing antibody breadth elicited in rhesus macaques by multimodal vaccines expressing the sivmac239 envelope.	antibodies that can neutralize diverse viral strains are likely to be an important component of a protective human immunodeficiency virus type 1 (hiv-1) vaccine. to this end, preclinical simian immunodeficiency virus (siv)-based nonhuman primate immunization regimens have been designed to evaluate and enhance antibody-mediated protection. however, these trials often rely on a limited selection of siv strains with extreme neutralization phenotypes to assess vaccine-elicited antibody activity. to ...	2015	26018167
two-year follow-up of macaques developing intermittent control of the human immunodeficiency virus homolog simian immunodeficiency virus sivmac251 in the chronic phase of infection.	off-therapy control of viremia by hiv-infected individuals has been associated with two likely players: a restricted viral reservoir and an efficient cell-mediated immune response. we previously showed that a combination of highly suppressive antiretroviral therapy and two experimental drugs, i.e., auranofin and buthionine sulfoximine, was able to reduce the viral reservoir, elicit efficient cell-mediated antiviral responses, and induce intermittent posttherapy viral load control in chronically ...	2015	25972547
chemokine-adjuvanted electroporated dna vaccine induces substantial protection from simian immunodeficiency virus vaginal challenge.	there have been encouraging results for the development of an effective hiv vaccine. however, many questions remain regarding the quality of immune responses and the role of mucosal antibodies. we addressed some of these issues by using a simian immunodeficiency virus (siv) dna vaccine adjuvanted with plasmid-expressed mucosal chemokines combined with an intravaginal siv challenge in rhesus macaque (rhm) model. we previously reported on the ability of ccr9 and ccr10 ligand (l) adjuvants to enhan ...	2016	25943275
oral administration of the nucleoside efda (4'-ethynyl-2-fluoro-2'-deoxyadenosine) provides rapid suppression of hiv viremia in humanized mice and favorable pharmacokinetic properties in mice and the rhesus macaque.	like normal cellular nucleosides, the nucleoside reverse transcriptase (rt) inhibitor (nrti) 4'-ethynyl-2-fluoro-2'-deoxyadenosine (efda) has a 3'-hydroxyl moiety, and yet efda is a highly potent inhibitor of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) replication with activity against a broad range of clinically important drug-resistant hiv isolates. we evaluated the anti-hiv activity of efda in primary human cells and in hiv-infected humanized mice. efda exhibite ...	2015	25941222
accumulation of cytotoxic cd16+ nk cells in simian immunodeficiency virus-infected lymph nodes associated with in situ differentiation and functional anergy.	recent evidence suggests that even in treated infections, human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) replication may continue in lymph nodes (ln), serving as a potential virus reservoir. here we investigated the effects of lentivirus infection on natural killer (nk) cell frequencies, phenotypes, and functions in naive and acutely or chronically sivmac239-infected rhesus macaques. compared to that in naive animals, we observed a 3-fold-greater frequency of cytotoxi ...	2015	25903330
increased expression of cd169 on blood monocytes and its regulation by virus and cd8 t cells in macaque models of hiv infection and aids.	increased expression of cd169 on monocytes has been reported in hiv-1-infected humans. using rhesus macaque models of hiv infection, we sought to investigate whether simian immunodeficiency virus (siv) infection upregulates cd169 expression on monocytes/macrophages. we also sought to determine whether cd8 t cells and plasma viral load directly impact the expression of cd169 on monocytes during siv infection. we longitudinally assessed monocyte expression of cd169 during the course of siv infecti ...	2015	25891017
role for cfms in maintaining alternative macrophage polarization in siv infection: implications for hiv neuropathogenesis.	macrophage-colony stimulating factor (m-csf) has been implicated in hiv neuropathogenesis through its ability to modulate activation of macrophages (mφs) and microglia, as well as enhance the susceptibility of these cells to infection and promote virus production. we have recently reported that mφs accumulating perivascularly and within nodular lesions in archival brain tissue of simian immunodeficiency virus (siv)-infected rhesus macaques with encephalitis (sive) express m-csf. in contrast, il- ...	2015	25886134
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 ...	2015	25833043
behavioral, metabolic, and immune consequences of chronic alcohol or cannabinoids on hiv/aids: studies in the non-human primate siv model.	hiv-associated mortality has been significantly reduced with antiretroviral therapy (art), and hiv infection has become a chronic disease that frequently coexists with many disorders, including substance abuse (azar et al. drug alcohol depend 112:178-193, 2010; phillips et al. j gen int med 16:165, 2001). alcohol and drugs of abuse may modify host-pathogen interactions at various levels including behavioral, metabolic, and immune consequences of hiv infection, as well as the ability of the virus ...	2015	25795088
immunophenotype of simian immunodeficiency virus-infected cells in the spleen of a rhesus monkey.		2015	25760311
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 ...	2015	25754201
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.	2015	25715103
hiv-1 coreceptor cxcr4 antagonists promote clonal expansion of viral epitope-specific cd8+ t cells during acute siv infection in rhesus monkeys in vivo.	the underlying molecular mechanisms and the kinetics of t cell receptor (tcr) repertoire selection during administration of cxcr4 or ccr5 inhibitors in infection of aids viruses in vivo have remained largely unexplored. viral epitope-specific cd8(+) t lymphocytes play a dominant role in the control of hiv and simian immunodeficiency virus (siv). we hypothesized that blockade of cxcr4 or ccr5 might influence the clonal expansion of epitope-specific cd8(+) t cells, contributing to antiviral immune ...	2015	25714247
aav-expressed ecd4-ig provides durable protection from multiple shiv challenges.	long-term in vivo expression of a broad and potent entry inhibitor could circumvent the need for a conventional vaccine for hiv-1. adeno-associated virus (aav) vectors can stably express hiv-1 broadly neutralizing antibodies (bnabs). however, even the best bnabs neutralize 10-50% of hiv-1 isolates inefficiently (80% inhibitory concentration (ic80) > 5 μg ml(-1)), suggesting that high concentrations of these antibodies would be necessary to achieve general protection. here we show that ecd4-ig, a ...	2015	25707797
antibodies for hiv prevention in young women.	young women in sub-saharan africa bear a disproportionate hiv burden. they urgently require new hiv prevention approaches that they can use. this review provides an overview of the use of antiretrovirals for hiv preexposure prophylaxis (prep), highlighting some of the challenges with this technology and explores the potential role of mabs for hiv prevention in women.	2015	25700207
early glial activation precedes neurodegeneration in the cerebral cortex after siv infection: a 3d, multivoxel proton magnetic resonance spectroscopy study.	as ∼40% of hiv-infected individuals experience neurocognitive decline, we investigated whether proton magnetic resonance spectroscopic imaging ((1) h-mrsi) detects early metabolic abnormalities in the cerebral cortex of a simian immunodeficiency virus (siv)-infected rhesus monkey model of neuroaids.	2015	25689120
balance of cellular and humoral immunity determines the level of protection by hiv vaccines in rhesus macaque models of hiv infection.	a guiding principle for hiv vaccine design has been that cellular and humoral immunity work together to provide the strongest degree of efficacy. however, three efficacy trials of ad5-vectored hiv vaccines showed no protection. transmission was increased in two of the trials, suggesting that this vaccine strategy elicited cd4+ t-cell responses that provide more targets for infection, attenuating protection or increasing transmission. the degree to which this problem extends to other hiv vaccine ...	2015	25681373
macaque species susceptibility to simian immunodeficiency virus: increased incidence of siv central nervous system disease in pigtailed macaques versus rhesus macaques.	immune pressure exerted by mhc class i-restricted cytotoxic t cells drives the development of viral escape mutations, thereby regulating hiv disease progression. nonetheless, the relationship between host immunity and hiv central nervous system (cns) disease remains poorly understood. the simian immunodeficiency virus (siv) macaque model recapitulates key features of hiv infection including development of aids and cns disease. to investigate cell-mediated immunity regulating siv cns disease prog ...	2015	25672885
african green monkey trim5α restriction in simian immunodeficiency virus-specific rhesus macaque effector cd4 t cells enhances their survival and antiviral function.	the expression of xenogeneic trim5α proteins can restrict infection in various retrovirus/host cell pairings. previously, we have shown that african green monkey trim5α (agmtrim5α) potently restricts both human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus mac239 (siv(mac239)) replication in a transformed human t-cell line (l. v. coren, et al., retrovirology 12:11, 2015, http://dx.doi.org/10.1186/s12977-015-0137-9). to assess agmtrim5α restriction in primary cells, we t ...	2015	25653448
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 ...	2015	25626488
simian immunodeficiency virus infection evades vaccine-elicited antibody responses to v2 region.	an effective aids vaccine should elicit protective antibody responses against hiv/simian immunodeficiency virus (siv) infection. we recently reported that mucosal priming with a replicating modified vaccinia tiantan virus (mvttgpe)-based vaccine regimen induces durable protection against pathogenic sivmac239 infection in rhesus monkeys. here, we aim to conduct a comprehensive analysis on antigenic determinants recognized by specific antibody responses generated by vaccination and sivmac239 infec ...	2015	25622057
b cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.	chronic-phase hiv and simian immunodeficiency virus (siv) replication is reduced by as much as 10,000-fold in elite controllers (ecs) compared with typical progressors (tps), but sufficient viral replication persists in ec tissues to allow viral sequence evolution and induce excess immune activation. here we show that productive siv infection in rhesus monkey ecs, but not tps, is markedly restricted to cd4(+) follicular helper t (tfh) cells, suggesting that these ec monkeys' highly effective siv ...	2015	25599132
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 ...	2015	25591175
a long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal shiv challenge.	long-acting gsk1265744 (gsk744 la) is a strand transfer inhibitor of the hiv/siv (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (prep) agent in a low-dose intrarectal shiv (simian-human immunodeficiency virus) rhesus macaque challenge model. we examined the pharmacokinetics and efficacy of gsk744 la as prep against repeat high-dose intravaginal shiv challenge in female rhesus macaques treated with depo-provera (depot medroxyprogesterone acetate ...	2015	25589630
activated cd4+ccr5+ t cells in the rectum predict increased siv acquisition in sivgag/tat-vaccinated rhesus macaques.	an effective t-cell-based aids vaccine should induce strong hiv-specific cd8(+) t cells in mucosal tissues without increasing the availability of target cells for the virus. here, we evaluated five immunization strategies that include human adenovirus-5 (adhu5), chimpanzee adenovirus-6 (adc6) or -7 (adc7), vaccinia virus (vv), and dna given by electroporation (dna/ep), all expressing simian immunodeficiency virus group specific antigen/transactivator of transcription (siv(mac239gag/tat)). five g ...	2015	25550504
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 ...	2015	25549835
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, ...	2014	25530944
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 ...	2015	25489000
plasmodium infection reduces the volume of the viral reservoir in siv-infected rhesus macaques receiving antiretroviral therapy.	previous studies indicated that plasmodium infection activates the immune system, including memory cd4+ t cells, which constitute the reservoir of human immunodeficiency virus type-1 (hiv-1). therefore, we postulated that co-infection with malaria might activate the reservoir of hiv-1. to test this hypothesis, we used a rhesus macaque model of co-infection with malaria and simian immunodeficiency virus (siv), along with antiretroviral therapy (art).	2014	25487036
trim5α restriction affects clinical outcome and disease progression in simian immunodeficiency virus-infected rhesus macaques.	tripartite motif-containing protein 5α (trim5α) is considered to be a potential target for cell-based gene modification therapy against human immunodeficiency virus type 1 (hiv-1) infection. in the present study, we used a relevant rhesus macaque model of infection with simian immunodeficiency virus from sooty mangabey (sivsm) to evaluate the effect of trim5α restriction on clinical outcome. for macaques expressing a restrictive trim5 genotype, the disease outcomes of those infected with the wil ...	2015	25473059
the effects of an actriib receptor fc fusion protein ligand trap in juvenile simian immunodeficiency virus-infected rhesus macaques.	there are no approved therapies for muscle wasting in children infected with human immunodeficiency virus (hiv), which portends poor disease outcomes. to determine whether a soluble actriib receptor fc fusion protein (actriib.fc), a ligand trap for tgf-β/activin family members including myostatin, can prevent or restore loss of lean body mass and body weight in simian immunodeficiency virus (siv)-infected juvenile rhesus macaques (macaca mulatta). fourteen pair-housed, juvenile male rhesus macaq ...	2015	25466897
toll-like receptor 3 signaling inhibits simian immunodeficiency virus replication in macrophages from rhesus macaques.	toll-like receptor 3 (tlr3) recognizes double-stranded rna and induces multiple intracellular events responsible for innate antiviral immunity against viral infections. here we demonstrate that tlr3 signaling of monocyte-derived macrophages (mdm) from rhesus monkeys by poly i:c inhibited simian immunodeficiency virus (siv) infection and replication. investigation of the mechanisms showed that tlr3 activation resulted in the induction of type i and type iii interferons (ifns) and ifn-inducible an ...	2014	25453343
dysregulated mir-34a-sirt1-acetyl p65 axis is a potential mediator of immune activation in the colon during chronic simian immunodeficiency virus infection of rhesus macaques.	persistent gastrointestinal inflammation, a hallmark of progressive hiv/siv infection, causes disruption of the gastrointestinal epithelial barrier, microbial translocation, and generalized immune activation/inflammation driving aids progression. apart from protein regulators, recent studies strongly suggest critical roles for micrornas (mirnas) in regulating and managing certain aspects of the inflammatory process. to examine their immunoregulatory role, we profiled mirna expression in the colo ...	2015	25452565
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 ...	2014	25421506
targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.	α4β7 integrin-expressing cd4(+) t cells preferentially traffic to gut-associated lymphoid tissue (galt) and have a key role in hiv and simian immunodeficiency virus (siv) pathogenesis. we show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with sivmac251. in treated animals that became infected, the galt was significantly protected from infecti ...	2014	25419708
chronic administration of δ9-tetrahydrocannabinol induces intestinal anti-inflammatory microrna expression during acute simian immunodeficiency virus infection of rhesus macaques.	recreational and medical use of cannabis among human immunodeficiency virus (hiv)-infected individuals has increased in recent years. in simian immunodeficiency virus (siv)-infected macaques, chronic administration of δ9-tetrahydrocannabinol (δ9-thc) inhibited viral replication and intestinal inflammation and slowed disease progression. persistent gastrointestinal disease/inflammation has been proposed to facilitate microbial translocation and systemic immune activation and promote disease progr ...	2015	25378491
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
transmitted/founder simian immunodeficiency virus envelope sequences in vesicular stomatitis and semliki forest virus vector immunized rhesus macaques.	identification of transmitted/founder simian immunodeficiency virus (siv) envelope sequences responsible for infection may prove critical for understanding hiv/siv mucosal transmission. we used single genome amplification and phylogenetic analyses to characterize transmitted/founder sivs both in the inoculum and in immunized-infected rhesus monkeys. single genome amplification of the sivsme660 inoculum revealed a maximum diversity of 1.4%. we also noted that the consensus sequence of the challen ...	2014	25360552
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
linking pig-tailed macaque major histocompatibility complex class i haplotypes and cytotoxic t lymphocyte escape mutations in simian immunodeficiency virus infection.	the influence of major histocompatibility complex class i (mhc-i) alleles on human immunodeficiency virus (hiv) diversity in humans has been well characterized at the population level. mhc-i alleles likely affect viral diversity in the simian immunodeficiency virus (siv)-infected pig-tailed macaque (macaca nemestrina) model, but this is poorly characterized. we studied the evolution of siv in pig-tailed macaques with a range of mhc-i haplotypes. siv(mac251) genomes were amplified from the plasma ...	2014	25275134
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 ...	2014	25274805
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
the mucosal expression pattern of interferon-ε in rhesus macaques.	type i ifns play an important role in innate and adaptive immunity against viral infections. a novel type i ifn, namely ifn-ε, which can protect against vaginal transmission of hsv2 and chlamydia muridarum bacterial infection, has been described in mice and humans. nevertheless, the principle cell type and the expression pattern of ifn-ε in tissues remain uncertain. in addition, the expression of ifn-ε in indian rhesus macaques (macaca mulatta) has not been reported. here, we analyzed ifn-ε expr ...	2014	25139290
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
virus-host mucosal interactions during early siv rectal transmission.	to deepen our understanding of early rectal transmission of hiv-1, we studied virus-host interactions in the rectal mucosa using simian immunodeficiency virus (siv)-indian rhesus macaque model and mrna deep sequencing. we found that rectal mucosa actively responded to siv as early as 3 days post-rectal inoculation (dpi) and mobilized more robust responses at 6 and 10 dpi. our results suggest that the failure of the host to contain virus replication at the portal of entry is attributable to both ...	2014	25128762