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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
rhesus macaque ifitm3 gene polymorphisms and siv infection.interferon-induced transmembrane proteins (ifitms) have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. in particular, polymorphisms of the human ifitm3 gene have been shown to affect disease severity and progression in influenza a virus (fluav) and human immunodeficiency virus (hiv) infection, respectively. rhesus macaques (macaca mulatta) are commonly used to model human infections and the experimental inoculation of th ...201728257482
influence of plasma cell niche factors on the recruitment and maintenance of irf4hi plasma cells and plasmablasts in vaccinated, simian immunodeficiency virus-infected rhesus macaques with low and high viremia.in a recent study, we found that protection following simian immunodeficiency virus (siv) exposure correlated with rectal plasma cell frequency in vaccinated female rhesus macaques. we sought to determine if the same macaques maintained high mucosal plasma cell frequencies postinfection and if this translated to reduced viremia. although delayed siv acquisition did not predict subsequent viral control, alterations existed in the distribution of plasma cells and plasmablasts between macaques that ...201727928009
changes in circulating b cell subsets associated with aging and acute siv infection in rhesus macaques.aging and certain viral infections can negatively impact humoral responses in humans. to further develop the nonhuman primate (nhp) model for investigating b cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus b cell subsets. significant differences between human and macaque b cells included the proportions of cells within igd+ and switched memory populations and a prominent cd21-cd27+ unswitched memory population detected ...201728095513
what is the predictive value of animal models for vaccine efficacy in humans? rigorous simian immunodeficiency virus vaccine trials can be instructive.simian immunodeficiency virus (siv) challenge of rhesus macaques provides an invaluable tool to evaluate the clinical prospects of hiv-1 vaccine concepts. however, as with any animal model of human disease, it is crucial to understand the advantages and limitations of this system to maximize the translational value of siv vaccine studies. here, we discuss the importance of assessing the efficacy of vaccine prototypes using stringent siv challenge regimens that mimic hiv-1 transmission and pathog ...201728348034
mzc gel inhibits shiv-rt and hsv-2 in macaque vaginal mucosa and shiv-rt in rectal mucosa.the population council's microbicide gel mzc (also known as pc-1005) containing miv-150 and zinc acetate dihydrate (za) in carrageenan (cg) has shown promise as a broad-spectrum microbicide against hiv, herpes simplex virus (hsv), and human papillomavirus. previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (shiv-rt) infection, and reduction of vaginal hsv shedding in rhesus m ...201727552154
balancing trained immunity with persistent immune activation and the risk of simian immunodeficiency virus infection in infant macaques vaccinated with attenuated mycobacterium tuberculosis or mycobacterium bovis bcg vaccine.our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (hiv-1) and tuberculosis (tb) infections. the vaccine consists of an auxotroph mycobacterium tuberculosis strain that coexpresses hiv antigens. utilizing an infant rhesus macaque model, we have previously shown that this attenuated m. tuberculosis (amtb)-simian immunodeficiency virus (siv) vaccine is immunogenic, and although the vaccine did not prevent o ...201727655885
chronic binge alcohol-induced dysregulation of mitochondrial-related genes in skeletal muscle of simian immunodeficiency virus-infected rhesus macaques at end-stage disease.alcohol use disorders are more prevalent in hiv patients than the general population. both chronic alcohol consumption and hiv infection have been linked to mitochondrial dysregulation; and this is considered an important mechanism in the pathogenesis of muscle myopathy. this study investigated if chronic binge alcohol (cba) administration impairs the expression of genes involved in mitochondrial homeostasis in siv-infected macaques.201728069597
kinetics of myeloid-derived suppressor cell frequency and function during simian immunodeficiency virus infection, combination antiretroviral therapy, and treatment interruption.during chronic lentiviral infection, poor clinical outcomes correlate both with systemic inflammation and poor proliferative ability of hiv-specific t cells; however, the connection between the two is not clear. myeloid-derived suppressor cells (mdsc), which expand during states of elevated circulating inflammatory cytokines, may link the systemic inflammation and poor t cell function characteristic of lentiviral infections. although mdsc are partially characterized in hiv and siv infection, que ...201727974456
the chitinases expression is related to simian immunodeficiency virus encephalitis (sive) and in hiv encephalitis (hive).human immunodeficiency virus (hiv) infection can induce neurocognitive complications classified as hiv-associated neurocognitive disorder (hand). the chitinase family is associated with innate immunity cells and many infectious diseases.201727794455
menin mediates tat-induced neuronal apoptosis in brain frontal cortex of siv-infected macaques and in tat-treated cells.the molecular mechanisms involved in human immunodeficiency virus (hiv)-associated neurocognitive disorder (hand) remain poorly understood. it has been recently reported that hiv-1 tat transactivation requires menin, suggesting that menin may be involved in hand pathogenesis. but the role of menin is not clear. here, we found that protein level of menin was increased in simian-human immunodeficiency chimeric virus (shiv)-sf162.p4 and simian immunodeficiency virus (siv) sm543-3-infected rhesus ma ...201728178646
dynamic modulation of expression of lentiviral restriction factors in primary cd4(+) t cells following simian immunodeficiency virus infection.although multiple restriction factors have been shown to inhibit hiv/siv replication, little is known about their expression in vivo expression of 45 confirmed and putative hiv/siv restriction factors was analyzed in cd4(+) t cells from peripheral blood and the jejunum in rhesus macaques, revealing distinct expression patterns in naive and memory subsets. in both peripheral blood and the jejunum, memory cd4(+) t cells expressed higher levels of multiple restriction factors compared to naive cell ...201728100613
controlling multicycle replication of live-attenuated hiv-1 using an unnatural genetic switch.a safe and effective human immunodeficiency virus type 1 (hiv-1) vaccine is urgently needed, but remains elusive. while hiv-1 live-attenuated vaccine can provide potent protection as demonstrated in rhesus macaque-simian immunodeficiency virus model, the potential pathogenic consequences associated with the uncontrolled virus replication preclude such vaccine from clinical applications. we investigated a novel approach to address this problem by controlling live-attenuated hiv-1 replication thro ...201728106981
hiv-1 tat primes and activates microglial nlrp3 inflammasome-mediated neuroinflammation.neuroinflammation associated with hiv-1 infection is a problem affecting ∼50% of hiv-infected individuals. nlr family pyrin domain containing 3 (nlrp3) inflammasome has been implicated in hiv-induced microglial activation, but the mechanism(s) remain unclear. because hiv-1 transactivator of transcription (tat) protein continues to be present despite antiretroviral therapy and activates nf-kb, we hypothesized that tat could prime the nlrp3 inflammasome. we found a dose- and time-dependent inducti ...201728270571
accelerated disease progression and robust innate host response in aged sivmac239-infected chinese rhesus macaques is associated with enhanced immunosenescence.the elderly population infected with hiv-1 is often characterized by the rapid aids progression and poor treatment outcome, possibly because of immunosenescence resulting from both hiv infection and aging. however, this hypothesis remains to be fully tested. here, we studied 6 young and 12 old chinese rhesus macaques (chrm) over the course of three months after simian immunodeficiency virus (siv) sivmac239 infection. old chrm showed a higher risk of accelerated aids development than did young ma ...201728232735
administration of an activin receptor iib ligand trap protects male juvenile rhesus macaques from simian immunodeficiency virus-associated bone loss.hiv-infected individuals are at an increased risk of osteoporosis despite effective viral suppression. observations that myostatin null mice have increased bone mass led us to hypothesize that simian immunodeficiency virus (siv)-associated bone loss may be attenuated by blocking myostatin/tgfβ signaling. in this proof-of-concept study, pair-housed juvenile male rhesus macaques were inoculated with sivmac239. four weeks later, animals were treated with vehicle or fc-conjugated soluble activin rec ...201728132908
functional effector memory t cells contribute to protection from superinfection with heterologous simian immunodeficiency virus or simian-human immunodeficiency virus isolates in chinese rhesus macaques.many studies have revealed a protective effect of infection of an individual with an immunodeficiency virus against subsequent infection with a heterologous strain. however, the extent of protection against superinfection conferred by the first infection and the biological consequences of superinfection are not well understood. here, we report that a rhesus monkey model of mucosal superinfection was established to investigate the protective immune response. protection against superinfection was ...201728110425
soluble tlr2 and 4 concentrations in cerebrospinal fluid in hiv/siv-related neuropathological conditions.hiv in the central nervous system (cns) mainly infects microglial cells which are known to express toll-like receptors (tlrs). this paper aimed to study the role of soluble tlr2 (stlr2), stlr4, and other inflammatory markers in cerebrospinal fluid (csf) in hiv/simian immunodeficiency virus (siv)-related neurological sequelae. we determined stlr2 and stlr4 levels in csf and serum/plasma of siv-infected rhesus macaques with and without neurological sequelae, as well as in hiv-infected patients wit ...201727882497
adjuvanting a simian immunodeficiency virus vaccine with toll-like receptor ligands encapsulated in nanoparticles induces persistent antibody responses and enhanced protection in trim5α restrictive macaques.our previous work has shown that antigens adjuvanted with ligands specific for toll-like receptor 4 (tlr4) and tlr7/8 encapsulated in poly(lactic-co-glycolic) acid (plga)-based nanoparticles (nps) induce robust and durable immune responses in mice and macaques. we investigated the efficacy of these np adjuvants in inducing protective immunity against simian immunodeficiency virus (siv). rhesus macaques (rms) were immunized with nps containing tlr4 and tlr7/8 agonists mixed with soluble recombina ...201727928002
vpx overcomes a samhd1-independent block to hiv reverse transcription that is specific to resting cd4 t cells.early after entry into monocytes, macrophages, dendritic cells, and resting cd4 t cells, hiv encounters a block, limiting reverse transcription (rt) of the incoming viral rna genome. in this context, dntp triphosphohydrolase sam domain and hd domain-containing protein 1 (samhd1) has been identified as a restriction factor, lowering the concentration of dntp substrates to limit rt. the accessory lentiviral protein x (vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, so ...201728228523
evaluation of vaginal drug levels and safety of a locally administered glycerol monolaurate cream in rhesus macaques.the human immunodeficiency virus (hiv) epidemic affects millions of people worldwide. as women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. glycerol monolaurate (gml), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. however, due to its low aqueous solubility, fabrication of high dose formulations of gml has proven difficult. we describ ...201728389267
epithelium-innate immune cell axis in mucosal responses to siv.in the siv (simian immunodeficiency virus)-rhesus macaque model of hiv-1 (human immunodeficiency virus type i) transmission to women, one hallmark of the mucosal response to exposure to high doses of siv is cd4 t-cell recruitment that fuels local virus expansion in early infection. in this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede cd4 t-cell recruitment. we show that vaginal exposure to the siv inoculum rapidly induces che ...201727435105
plasmablast response to primary rhesus cytomegalovirus infection in a monkey model of congenital cmv transmission.human cytomegalovirus (hcmv) is the most common congenital infection worldwide, and the leading infectious cause of neurologic deficits and hearing loss in newborns. development of a maternal hcmv vaccine to prevent vertical virus transmission is a high priority, yet protective maternal immune responses following acute infection are poorly understood. to characterize the maternal humoral immune response to primary cmv infection, we investigated the plasmablast and early antibody repertoire using ...201728298291
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