| recombinant yellow fever vaccine virus 17d expressing simian immunodeficiency virus sivmac239 gag induces siv-specific cd8+ t-cell responses in rhesus macaques. | here we describe a novel vaccine vector for expressing human immunodeficiency virus (hiv) antigens. we show that recombinant attenuated yellow fever vaccine virus 17d expressing simian immunodeficiency virus sivmac239 gag sequences can be used as a vector to generate siv-specific cd8(+) t-cell responses in the rhesus macaque. priming with recombinant bcg expressing siv antigens increased the frequency of these siv-specific cd8(+) t-cell responses after recombinant yf17d boosting. these recombina ... | 2010 | 20089645 |
| trim5alpha modulates immunodeficiency virus control in rhesus monkeys. | the cytoplasmic trim5alpha proteins of certain mammalian lineages efficiently recognize the incoming capsids of particular retroviruses and potently restrict infection in a species-specific manner. successful retroviruses have evolved capsids that are less efficiently recognized by the trim5alpha proteins of the natural hosts. to address whether trim5alpha contributes to the outcome of retroviral infection in a susceptible host species, we investigated the impact of trim5 polymorphisms in rhesus ... | 2010 | 20107597 |
| local replication of simian immunodeficiency virus in the breast milk compartment of chronically-infected, lactating rhesus monkeys. | breast milk transmission remains a major mode of infant hiv acquisition, yet anatomic and immunologic forces shaping virus quasispecies in milk are not well characterized. in this study, phylogenic analysis of envelope sequences of milk siv variants revealed groups of nearly identical viruses, indicating local virus production. however, comparison of the patterns and rates of ctl escape of blood and milk virus demonstrated only subtle differences between the compartments. these findings suggest ... | 2010 | 20122164 |
| in vivo cd8+ t-cell suppression of siv viremia is not mediated by ctl clearance of productively infected cells. | the cd8+ t-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. we studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (siv) infected rhesus macaques following cd8+ t-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with siv. as previously described, plasma viral load (vl) increased followin ... | 2010 | 20126442 |
| dynamics of haplotype frequency change in a cd8+tl epitope of simian immunodeficiency virus. | deep pyrosequencing of a cd8+tl epitope from the tat protein of simian immunodeficiency virus (siv) from four infected rhesus macaques carrying the restricting mhc allele (mamu-a*01) for that epitope, revealed that natural selection favoring escape mutations led to an increase in the frequency of haplotypes in the epitope region that differed from the inoculum. after 20 weeks of infection, a new sequence haplotype in the epitope region had increased to a frequency greater than 50% in each of the ... | 2010 | 20149896 |
| induction of antibody-mediated neutralization in sivmac239 by a naturally acquired v3 mutation. | achieving humoral immunity against human immunodeficiency virus (hiv) is a major obstacle in aids vaccine development. despite eliciting robust humoral responses to hiv, exposed hosts rarely produce broadly neutralizing antibodies. the present study utilizes simian immunodeficiency virus (siv) to identify viral epitopes that conferred antibody neutralization to clone siv/17e-cl, an in vivo variant derived from neutralization resistant sivmac239. neutralization assays using rhesus macaque monoclo ... | 2010 | 20153009 |
| interleukin 18 and cardiovascular disease in hiv-1 infection: a partner in crime? | cardiovascular disease has been frequent in hiv-infected patients both before and after the advent of antiretroviral therapy (haart). the pathogenic basis for the increase of cardiovascular disease, in particular myocardial lesions, may involve hiv-1 itself or other mechanisms including endothelial dysfunction, activation of proinflammatory cytokines, and changes in platelets, which lead to atherosclerotic lesions of blood vessels. in the last decade, among the proinflammatory cytokines, interle ... | 2010 | 20216908 |
| high viremia is associated with high levels of in vivo major histocompatibility complex class i downregulation in rhesus macaques infected with simian immunodeficiency virus sivmac239. | human and simian immunodeficiency viruses (hiv and siv) downregulate major histocompatibility complex class i (mhc-i) molecules from the surface of infected cells. although this activity is conserved across viral isolates, its importance in aids pathogenesis is not clear. we therefore developed an assay to detect the level of mhc-i expression of siv-infected cells directly ex vivo. here we show that the extent of mhc-i downregulation is greatest in sivmac239-infected macaques that never effectiv ... | 2010 | 20219903 |
| peripheral blood cd4 and cd8 double-positive t cells of rhesus macaques become vulnerable to simian immunodeficiency virus by in vitro stimulation due to the induction of ccr5. | in vivo simian immunodeficiency virus (siv) challenge of macaques demonstrated the earlier disappearance of cd4 and cd8 double-positive (dp) t cells than cd4 single-positive t cells, although its mechanism remains unclear. here we found that peripheral dp t cells were readily induced to express ccr5, a secondary receptor for siv, by in vitro stimulation with either concanavalin a or anti-cd3/cd28 monoclonal antibodies. activated dp t cells were more vulnerable to siv infection, indicating that t ... | 2010 | 20224239 |
| identification of 81lgxgxxixw89 and 171edrw174 domains from human immunodeficiency virus type 1 vif that regulate apobec3g and apobec3f neutralizing activity. | the human cytidine deaminases apobec3g (a3g) and apobec3f (a3f) potently restrict human immunodeficiency virus type 1 (hiv-1) replication, but they are neutralized by the viral protein vif. vif bridges a3g and a3f with a cullin 5 (cul5)-based e3 ubiquitin ligase and mediates their proteasomal degradation. this mechanism has been extensively studied, and several vif domains have been identified that are critical for a3g and a3f neutralization. here, we identified two additional domains. via seque ... | 2010 | 20335268 |
| systemic spironucleosis in 2 immunodeficient rhesus macaques (macaca mulatta). | spironucleus spp are parasites of fish and terrestrial vertebrates, including mice and turkeys, that rarely cause extraintestinal disease. two rhesus macaques (macaca mulatta) were experimentally inoculated with simian immunodeficiency virus mac251. both progressed to simian acquired immune deficiency syndrome within 1 year of inoculation and developed systemic protozoal infections in addition to common opportunistic infections, including rhesus cytomegalovirus, rhesus lymphocryptovirus, and rhe ... | 2010 | 20351359 |
| autologous neutralizing antibodies to the transmitted/founder viruses emerge late after simian immunodeficiency virus sivmac251 infection of rhesus monkeys. | while the simian immunodeficiency virus (siv)-infected rhesus monkey is an important animal model for human immunodeficiency virus type 1 (hiv-1) infection of humans, much remains to be learned about the evolution of the humoral immune response in this model. in hiv-1 infection, autologous neutralizing antibodies emerge 2 to 3 months after infection. however, the ontogeny of the siv-specific neutralizing antibody response in mucosally infected animals has not been defined. we characterized the k ... | 2010 | 20357097 |
| depo-provera does not alter disease progression in sivmac-infected female chinese rhesus macaques. | depo-provera (medroxyprogesterone acetate), a long-acting derivative of progesterone, is utilized during many nonhuman primate microbicide studies to facilitate simian immunodeficiency virus (siv) infection by thinning the vaginal epithelium. to date, the systemic effects of this steroid hormone in regard to siv/hiv pathogenesis are not well understood, but an increase in infection rates and lymphoproliferation following progesterone application has been reported. therefore, a proactive study us ... | 2010 | 20377424 |
| expression, purification, crystallization and preliminary x-ray diffraction analysis of rhesus macaque cd8alphaalpha homodimer. | as a t-cell co-receptor, cd8 binds to mhc class i molecules and plays a pivotal role in the activation of cytotoxic t lymphocytes. to date, structures of cd8 have been solved for two different mammals: human and mouse. the infection of rhesus macaques (macaca mulatta) by simian immunodeficiency virus (siv) is the best animal model for studying hiv. in this study, the rhesus macaque cd8 (rcd8) alphaalpha homodimer was obtained and rcd8alpha exodomain protein crystals were successfully obtained fo ... | 2010 | 20383016 |
| differential cell surface expression of rhesus macaque's major histocompatibility complex class i alleles mamu-b*1703 and mamu-b*0101. | the major histocompatibility complex class i allele mamu-b*17 of rhesus macaques is an elite controller of simian immunodeficiency virus (siv) infection whereas mamu-b*01 has no inhibitory effect on siv replication. the mechanism is still elusive. in this study, the so-called "missing g" in the leading peptide sequence of mamu-b*1703 allele was artificially inserted back through pcr amplification, and the new sequence was renamed as mamu-b*1703(+g). the plasmids harboring mamu-b*1703, mamu-b*170 ... | 2010 | 20383467 |
| antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in mf59 adjuvant. | we have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus shiv(sf162p4) following sequential immunization with alphavirus replicon particles (vrp) of a chimeric recombinant vee/sin alphavirus (derived from venezuelan equine encephalitis virus [vee] and the sindbis virus [sin]) encoding human immunodeficiency virus type 1 hiv-1(sf162) gp140deltav2 envelope (env) and trimeric env protein in mf59 adjuvant ... | 2010 | 20392857 |
| variability in a dominant block to siv early reverse transcription in rhesus monkey cells predicts in vivo viral replication and time to death. | while it has long been appreciated that there is considerable variability in host containment of hiv/siv replication, the determinants of that variability are not fully understood. previous studies demonstrated that the degree of permissivity of a macaque's peripheral blood mononuclear cells (pbmc) for infection with simian immunodeficiency virus (siv) in vitro predicted that animal's peak plasma virus rna levels following siv infection in vivo. the present study was conducted to define the mech ... | 2010 | 20416115 |
| frequency of the major histocompatibility complex mamu-a*01 allele in experimental rhesus macaques in china. | in indian rhesus macaques, the major histocompatibility complex mamu gene, especially the mamu-a*01 allele, plays an important role in simian immunodeficiency virus susceptibility and disease progression. the mamu-a*01 allele is one of the protective genes mostly being studied in simian acquired immunodeficiency syndrome. | 2010 | 20444001 |
| multiple vaccine-elicited nonneutralizing antienvelope antibody activities contribute to protective efficacy by reducing both acute and chronic viremia following simian/human immunodeficiency virus shiv89.6p challenge in rhesus macaques. | we have shown that following priming with replicating adenovirus type 5 host range mutant (ad5hr)-human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) recombinants, boosting with gp140 envelope protein enhances acute-phase protection against intravenous simian/human immunodeficiency virus (shiv)(89.6p) challenge compared to results with priming and no boosting or boosting with an hiv polypeptide representing the cd4 binding site of gp120. we retrospectively analyzed antibodies ... | 2010 | 20444898 |
| a limited number of simian immunodeficiency virus (siv) env variants are transmitted to rhesus macaques vaginally inoculated with sivmac251. | single-genome amplification (sga) and sequencing of hiv-1 rna in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. use of this strategy as a means for identifying transmitted viruses suggested that intrarectal simian immunodeficiency virus (siv) inoculation of macaques recapitulates key features of human rectal infection. however, no studies have used the sga strategy to identify vaginally tra ... | 2010 | 20463069 |
| proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated neuroaids. | despite the advent of highly active anti-retroviral therapy (haart), hiv-associated neurocognitive disorders continue to be a significant problem. in efforts to understand and alleviate neurocognitive deficits associated with hiv, we used an accelerated simian immunodeficiency virus (siv) macaque model of neuroaids to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury. | 2010 | 20479889 |
| the most common chinese rhesus macaque mhc class i molecule shares peptide binding repertoire with the hla-b7 supertype. | of the two rhesus macaque subspecies used for aids studies, the simian immunodeficiency virus-infected indian rhesus macaque (macaca mulatta) is the most established model of hiv infection, providing both insight into pathogenesis and a system for testing novel vaccines. despite the chinese rhesus macaque potentially being a more relevant model for aids outcomes than the indian rhesus macaque, the chinese-origin rhesus macaques have not been well-characterized for their major histocompatibility ... | 2010 | 20480161 |
| lineage-specific t-cell reconstitution following in vivo cd4+ and cd8+ lymphocyte depletion in nonhuman primates. | many features of t-cell homeostasis in primates are still unclear, thus limiting our understanding of aids pathogenesis, in which t-cell homeostasis is lost. here, we performed experiments of in vivo cd4(+) or cd8(+) lymphocyte depletion in 2 nonhuman primate species, rhesus macaques (rms) and sooty mangabeys (sms). whereas rms develop aids after infection with simian immunodeficiency virus (siv), siv-infected sms are typically aids-resistant. we found that, in both species, most cd4(+) or cd8(+ ... | 2010 | 20484087 |
| downregulation of robust acute type i interferon responses distinguishes nonpathogenic simian immunodeficiency virus (siv) infection of natural hosts from pathogenic siv infection of rhesus macaques. | the mechanisms underlying the aids resistance of natural hosts for simian immunodeficiency virus (siv) remain unknown. recently, it was proposed that natural siv hosts avoid disease because their plasmacytoid dendritic cells (pdcs) are intrinsically unable to produce alpha interferon (ifn-alpha) in response to siv rna stimulation. however, here we show that (i) acute siv infections of natural hosts are associated with a rapid and robust type i ifn response in vivo, (ii) pdcs are the principal in ... | 2010 | 20484518 |
| methamphetamine increases brain viral load and activates natural killer cells in simian immunodeficiency virus-infected monkeys. | methamphetamine (meth) abuse increases risky behaviors that contribute to the spread of hiv infection. in addition, because hiv and meth independently affect physiological systems including the central nervous system, hiv-induced disease may be more severe in drug users. we investigated changes in blood and brain viral load as well as differences in immune cells in chronically simian immunodeficiency virus-infected rhesus macaques that were either administered meth or used as controls. although ... | 2010 | 20489154 |
| neutralizing antibodies in siv control: co-impact with t cells. | human immunodeficiency virus type 1 (hiv-1) and pathogenic simian immunodeficiency virus (siv)-infected naïve hosts experience a characteristic absence of early and potent virus-specific neutralizing antibody (nab) responses preceding establishment of persistent infection. yet conversely, we have recently shown that nabs passively immunized in rhesus macaques at early post-siv challenge are capable of playing a critical role in non-sterile viremia control with implications of antibody-enhanced a ... | 2010 | 20510737 |
| limited contribution of mucosal iga to simian immunodeficiency virus (siv)-specific neutralizing antibody response and virus envelope evolution in breast milk of siv-infected, lactating rhesus monkeys. | breast milk transmission of human immunodeficiency virus (hiv) remains an important mode of infant hiv acquisition. interestingly, the majority of infants remain uninfected during prolonged virus exposure via breastfeeding, raising the possibility that immune components in milk prevent mucosal virus transmission. hiv-specific antibody responses are detectable in the milk of hiv-infected women and simian immunodeficiency virus (siv)-infected monkeys; however, the role of these humoral responses i ... | 2010 | 20519381 |
| th17 cells and hiv infection. | this review summarizes the recent literature about the potential perturbation and role of th17 cells in hiv pathogenesis. we discuss the recent findings on th17 deficiency in hiv/simian immunodeficiency virus (siv) infection and how this deficiency may impact the mucosal host defenses, potentially contributing to chronic immune activation. | 2010 | 20543592 |
| th17 cells, hiv and the gut mucosal barrier. | we will present recent studies on a subset of cd4 t helper cells, th17 cells, that appears to be critical for regulating gut mucosal immune responses against extracellular microbial pathogens and may serve as a link between innate and adaptive immune responses. implications of the loss of th17 cd4 t cells in hiv infection will be discussed in relation to the chronic immune activation and hiv pathogenesis. | 2010 | 20543596 |
| th17 cells, job's syndrome and hiv: opportunities for bacterial and fungal infections. | patients with hyper ige syndrome (hies) share with hiv patients a predisposition to infections, including candidiasis in autosomal dominant hies (ad-hies) and molluscum contagiosum and other viral infections in other disorders of elevated ige with infectious predilections. this review highlights the underlying pathogenesis of these diseases and their relevance to hiv infection. | 2010 | 20543597 |
| contributions of mamu-a*01 status and trim5 allele expression, but not ccl3l copy number variation, to the control of sivmac251 replication in indian-origin rhesus monkeys. | ccl3 is a ligand for the hiv-1 co-receptor ccr5. there have recently been conflicting reports in the literature concerning whether ccl3-like gene (ccl3l) copy number variation (cnv) is associated with resistance to hiv-1 acquisition and with both viral load and disease progression following infection with hiv-1. an association has also been reported between ccl3l cnv and clinical sequelae of the simian immunodeficiency virus (siv) infection in vivo in rhesus monkeys. the present study was initia ... | 2010 | 20585621 |
| maintenance or emergence of chronic phase secondary cytotoxic t lymphocyte responses after loss of acute phase immunodominant responses does not protect siv-infected rhesus macaques from disease progression. | the simian immunodeficiency virus- (siv-) infected rhesus macaque is the preferred animal model for vaccine development, but the correlates of protection in this model are not completely understood. in this paper, we document the cytotoxic t lymphocyte (ctl) response to siv and its effects on viral evolution in an effort to identify events associated with disease progression regardless of mhc allele expression. we observed the evolution of epitopes targeted by ctls in a group of macaques that in ... | 2010 | 20589067 |
| limited cd4+ t cell proliferation leads to preservation of cd4+ t cell counts in siv-infected sooty mangabeys. | human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) infections result in chronic virus replication and progressive depletion of cd4+ t cells, leading to immunodeficiency and death. in contrast, 'natural hosts' of siv experience persistent infection with high virus replication but no severe cd4+ t cell depletion, and remain aids-free. one important difference between pathogenic and non-pathogenic infections is the level of activation and proliferation of cd4+ t cells. we an ... | 2010 | 20591864 |
| identification of a critical t(q/d/e)x5adx2(i/l) motif from primate lentivirus vif proteins that regulate apobec3g and apobec3f neutralizing activity. | primate lentiviruses are unique in that they produce several accessory proteins to help in the establishment of productive viral infection. the major function of these proteins is to clear host resistance factors that inhibit viral replication. vif is one of these proteins. it functions as an adaptor that binds to the cytidine deaminases apobec3g (a3g) and apobec3f (a3f) and bridges them to a cullin 5 (cul5) and elongin (elo) b/c e3 ubiquitin ligase complex for proteasomal degradation. so far, 1 ... | 2010 | 20592083 |
| macaques vaccinated with simian immunodeficiency virus sivmac239delta nef delay acquisition and control replication after repeated low-dose heterologous siv challenge. | an effective human immunodeficiency virus (hiv) vaccine will likely need to reduce mucosal transmission and, if infection occurs, control virus replication. to determine whether our best simian immunodeficiency virus (siv) vaccine can achieve these lofty goals, we vaccinated eight indian rhesus macaques with sivmac239delta nef and challenged them intrarectally (i.r.) with repeated low doses of the pathogenic heterologous swarm isolate sivsme660. we detected a significant reduction in acquisition ... | 2010 | 20592091 |
| impact of short-term combined antiretroviral therapy on brain virus burden in simian immunodeficiency virus-infected and cd8+ lymphocyte-depleted rhesus macaques. | antiretroviral drugs suppress virus burden in the cerebrospinal fluid of hiv-infected individuals; however, the direct effect of antiretrovirals on virus replication in brain parenchyma is poorly understood. we investigated the effect of short-term combined antiretroviral therapy (cart) on brain virus burden in rhesus monkeys using the cd8-depletion model of accelerated simian immunodeficiency virus (siv) encephalitis. four monkeys received cart (consisting of the nonpenetrating agents pmpa and ... | 2010 | 20595631 |
| fundamental difference in the content of high-mannose carbohydrate in the hiv-1 and hiv-2 lineages. | the virus-encoded envelope proteins of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) typically contain 26 to 30 sites for n-linked carbohydrate attachment. n-linked carbohydrate can be of three major types: high mannose, complex, or hybrid. the lectin proteins from galanthus nivalis (gna) and hippeastrum hybrid (hha), which specifically bind high-mannose carbohydrate, were found to potently inhibit the replication of a pathogenic cloned siv from rhesus macaques, sivm ... | 2010 | 20610711 |
| generation of a dual rt env shiv that is infectious in rhesus macaques. | the best current animal model for hiv infection and evaluation of antiviral compounds is the simian-human immunodeficiency virus (shiv)/macaque system. there are multiple recombinant shivs available, but these viruses have limitations in evaluating combination drug strategies for prevention. drug combinations that target reverse transcriptase (rt, either nrti or nnrti) and envelope (entry or fusion inhibitors) have to be tested separately, which does not permit the assessment of additive, synerg ... | 2010 | 20618587 |
| microbial translocation in simian immunodeficiency virus (siv)-infected rhesus monkeys (macaca mulatta). | chronic immune activation is a hallmark of hiv infection and has been postulated as major factor in the pathogenesis of aids. recent evidence suggests that activation of immune cells is triggered by microbial translocation through the impaired gastrointestinal barrier. | 2010 | 20618590 |
| increased cd4+ t cell levels during il-7 administration of antiretroviral therapy-treated simian immunodeficiency virus-positive macaques are not dependent on strong proliferative responses. | cd4(+) t cell depletion is a fundamental component of hiv infection and aids pathogenesis and is not always reversed following antiretroviral therapy (art). in this study, the siv-infected rhesus macaque model was used to assess recombinant simian il-7 in its glycosylated form (rsil-7gly) to enhance regeneration of cd4(+) t cells, particularly the crucial central memory compartment, after art. we assessed the impact of rsil-7gly administration as single injections and as a cluster of three doses ... | 2010 | 20622118 |
| clonal repertoires of virus-specific cd8+ t lymphocytes are shared in mucosal and systemic compartments during chronic simian immunodeficiency virus infection in rhesus monkeys. | because it is thought that mucosal tissues play a fundamental role in early hiv/siv infection, it is crucial to understand the virus-specific responses in mucosal tissues to facilitate devising strategies to prevent and control these infections. we have employed tcr repertoire analyses to define the clonal composition of a dominant siv epitope-specific cd8(+) t cell population in mucosal and systemic compartments of siv-infected rhesus monkeys during both acute and chronic infection. we show tha ... | 2010 | 20624939 |
| diversity of mhc class i genes in burmese-origin rhesus macaques. | rhesus macaques (macaca mulatta) are widely used in developing a strategy for vaccination against human immunodeficiency virus by using simian immunodeficiency virus infection as a model system. because the genome diversity of major histocompatibility complex (mhc) is well known to control the immune responsiveness to foreign antigens, mhc loci in indian- and chinese-origin macaques used in the experiments have been characterized, and it was revealed that the diversity of mhc in macaques was lar ... | 2010 | 20640416 |
| recombinant varicella vaccines induce neutralizing antibodies and cellular immune responses to siv and reduce viral loads in immunized rhesus macaques. | the development of an effective aids vaccine remains one of the highest priorities in hiv research. the live, attenuated varicella-zoster virus (vzv) oka vaccine, safe and effective for prevention of chickenpox and zoster, also has potential as a recombinant vaccine against other pathogens, including human immunodeficiency virus (hiv). the simian varicella model, utilizing simian varicella virus (svv), offers an approach to evaluate recombinant varicella vaccine candidates. recombinant svv (rsvv ... | 2010 | 20654666 |
| mechanisms underlying γδ t-cell subset perturbations in siv-infected asian rhesus macaques. | t cells that express the γδ t-cell receptor, which recognize microbial or stress-induced antigens, represent a minority of blood t cells but constitute a major proportion of intraepithelial lymphocytes in the gastrointestinal mucosa. as microbial products have been shown to translocate from the gastrointestinal tract into circulation in chronically hiv/simian immunodeficiency virus (siv)-infected individuals, we conducted a study of vδ1 and vδ2 t-cell frequency, phenotype, and function in blood, ... | 2010 | 20660793 |
| viral decay kinetics in the highly active antiretroviral therapy-treated rhesus macaque model of aids. | to prevent progression to aids, persons infected with human immunodeficiency virus type 1 (hiv-1) must remain on highly active antiretroviral therapy (haart) indefinitely since this modality does not eradicate the virus. the mechanisms involved in viral persistence during haart are poorly understood, but an animal model of haart could help elucidate these mechanisms and enable studies of hiv-1 eradication strategies. due to the specificity of non-nucleoside reverse transcriptase (rt) inhibitors ... | 2010 | 20668516 |
| characterization of siv in the oral cavity and in vitro inhibition of siv by rhesus macaque saliva. | human immunodeficiency virus (hiv) infections are rarely acquired via an oral route in adults. previous studies have shown that human whole saliva inhibits hiv infection in vitro, and multiple factors present in human saliva have been shown to contribute to this antiviral activity. despite the widespread use of simian immunodeficiency virus (siv)-infected rhesus macaques as models for hiv pathogenesis and transmission, few studies have monitored siv in the oral cavity of infected rhesus macaques ... | 2010 | 20672998 |
| plasma proteomic analysis of simian immunodeficiency virus infection of rhesus macaques. | lentiviral replication in its target cells affects a delicate balance between cellular cofactors required for virus propagation and immunoregulation for host defense. to better elucidate cellular proteins linked to viral infection, we tested plasma from rhesus macaques infected with the simian immunodeficiency viral strain sivsmm9, prior to, 10 days (acute), and 49 weeks (chronic) after viral infection. changes in plasma protein content were measured by quantitative mass spectrometry by isobaric ... | 2010 | 20677826 |
| low-dose mucosal simian immunodeficiency virus infection restricts early replication kinetics and transmitted virus variants in rhesus monkeys. | defining the earliest virologic events following human immunodeficiency virus type 1 (hiv-1) transmission may be critical for the design of vaccine strategies aimed at blocking acquisition of hiv-1 infection. in particular, the length of the eclipse phase and the number of transmitted virus variants may define the window in which a prophylactic vaccine must act. here we show that the dose of the virus inoculum affects these key virologic parameters following intrarectal simian immunodeficiency v ... | 2010 | 20686016 |
| envelope-modified single-cycle simian immunodeficiency virus selectively enhances antibody responses and partially protects against repeated, low-dose vaginal challenge. | immunization of rhesus macaques with strains of simian immunodeficiency virus (siv) that are limited to a single cycle of infection elicits t-cell responses to multiple viral gene products and antibodies capable of neutralizing lab-adapted siv, but not neutralization-resistant primary isolates of siv. in an effort to improve upon the antibody responses, we immunized rhesus macaques with three strains of single-cycle siv (scsiv) that express envelope glycoproteins modified to lack structural feat ... | 2010 | 20702641 |
| emergence of simian immunodeficiency virus-specific cytotoxic cd4+ t cells and increased humoral responses correlate with control of rebounding viremia in cd8-depleted macaques infected with rev-independent live-attenuated simian immunodeficiency virus. | indian rhesus macaques infected with the rev-independent live-attenuated sivmac239 strains control viremia to undetectable levels, have persistent but low cellular and humoral anti-siv responses, and show no signs of immune deficiency. to analyze the immune mechanisms responsible for viral control, five macaques infected at day 1 after birth were subjected to cd8(+) cell depletion at 6.7 y postinfection. this resulted in viremia increases to 3.7-5.5 log(10) rna copies, supporting a role of cd8-m ... | 2010 | 20702730 |
| simian immunodeficiency virus selectively infects proliferating cd4+ t cells in neonatal rhesus macaques. | infants infected with hiv have a more severe course of disease and persistently higher viral loads than hiv-infected adults. however, the underlying pathogenesis of this exacerbation remains obscure. here we compared the rate of cd4(+) and cd8(+) t-cell proliferation in intestinal and systemic lymphoid tissues of neonatal and adult rhesus macaques, and of normal and age-matched simian immunodeficiency virus (siv)-infected neonates. the results demonstrate infant primates have much greater rates ... | 2010 | 20716768 |
| cd8+ t cell recognition of cryptic epitopes is a ubiquitous feature of aids virus infection. | vaccines designed to elicit aids virus-specific cd8+ t cells should engender broad responses. emerging data indicate that alternate reading frames (arfs) of both human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) encode cd8+ t cell epitopes, termed cryptic epitopes. here, we show that siv-specific cd8+ t cells from siv-infected rhesus macaques target 14 epitopes in eight arfs during siv infection. animals recognized up to five epitopes, totaling nearly one-quarter of the ... | 2010 | 20739530 |
| damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. | the chronic phase of hiv infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or cd4(+) t cell count. recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically hiv-infected human ... | 2010 | 20808901 |
| simian immunodeficiency virus-specific cd4+ t cells from successful vaccinees target the siv gag capsid. | we recently demonstrated that vaccinated rhesus macaques controlled viral replication of a heterologous siv challenge. here, we analyzed anamnestic siv-specific cd4+ t-cell responses expanding immediately after challenge and show that successful vaccinees consistently targeted a short region of the gag-p27 capsid (amino acids 249-291). we have also defined the major histocompatibility complex class ii (mhc-ii) restricting alleles for several of these responses and show that dq-restricted cd4+ t- ... | 2010 | 20812010 |
| multiple sites in the n-terminal half of simian immunodeficiency virus capsid protein contribute to evasion from rhesus monkey trim5α-mediated restriction. | we previously reported that cynomolgus monkey (cm) trim5α could restrict human immunodeficiency virus type 2 (hiv-2) strains carrying a proline at the 120th position of the capsid protein (ca), but it failed to restrict those with a glutamine or an alanine. in contrast, rhesus monkey (rh) trim5α could restrict all hiv-2 strains tested but not simian immunodeficiency virus isolated from macaque (sivmac), despite its genetic similarity to hiv-2. | 2010 | 20825647 |
| interleukin-7 treatment counteracts ifn-α therapy-induced lymphopenia and stimulates siv-specific cytotoxic t lymphocyte responses in siv-infected rhesus macaques. | interferon-α (ifn-α)-based therapy is presently the standard treatment for hepatitis c virus (hcv)-infected patients. despite good effectiveness, this cytokine is associated with major side effects, including significant lymphopenia, that limits its use for hiv/hcv-coinfected patients. interleukin-7 (il-7) has recently shown therapeutic potential and safety in several clinical trials designed to demonstrate t-cell restoration in immunodeficient patients. the purpose of this study was to evaluate ... | 2010 | 20841508 |
| transgenic rhesus monkeys produced by gene transfer into early-cleavage-stage embryos using a simian immunodeficiency virus-based vector. | the development of transgenic technologies in monkeys is important for creating valuable animal models of human physiology so that the etiology of diseases can be studied and potential therapies for their amelioration may be developed. however, the efficiency of producing transgenic primate animals is presently very low, and there are few reports of success. we have developed an improved methodology for the production of transgenic rhesus monkeys, making use of a simian immunodeficiency virus (s ... | 2010 | 20870965 |
| cannabinoid administration attenuates the progression of simian immunodeficiency virus. | abstract δ(9)-tetrahydrocannabinol (δ(9)-thc), the primary psychoactive component in marijuana, is fda approved to ameliorate aids-associated wasting. because cannabinoid receptors are expressed on cells of the immune system, chronic δ(9)-thc use may impact hiv disease progression. we examined the impact of chronic δ(9)-thc administration (0.32 mg/kg im, 2 × daily), starting 28 days prior to inoculation with simian immunodeficiency virus (siv(mac251); 100 tcid(50)/ml, iv), on immune and metaboli ... | 2010 | 20874519 |
| a structural constraint for functional interaction between n-terminal and c-terminal domains in simian immunodeficiency virus capsid proteins. | the gag capsid (ca) is one of the most conserved proteins in highly-diversified human and simian immunodeficiency viruses (hiv and siv). understanding the limitations imposed on amino acid sequences in ca could provide valuable information for vaccine immunogen design or anti-hiv drug development. here, by comparing two pathogenic siv strains, sivmac239 and sivsme543-3, we found critical amino acid residues for functional interaction between the n-terminal and the c-terminal domains in ca. | 2010 | 20955553 |
| simian immunodeficiency virus from the sooty mangabey and rhesus macaque is modified with o-linked carbohydrate. | although stretches of serine and threonine are sometimes sites for o-linked carbohydrate attachment, specific sequence and structural determinants for o-linked attachment remain ill defined. the gp120 envelope protein of sivmac239 contains a serine-threonine-rich stretch of amino acids at positions 128 to 139. here we show that lectin protein from jackfruit seed (jacalin), which binds to non- and monosialylated core 1 o-linked carbohydrate, potently inhibited the replication of sivmac239. select ... | 2010 | 20962077 |
| macaque long-term nonprogressors resist superinfection with multiple cd8+ t cell escape variants of simian immunodeficiency virus. | human immunodeficiency virus (hiv)-positive individuals can be superinfected with different virus strains. individuals who control an initial hiv infection are therefore still at risk for subsequent infection with divergent viruses, but the barriers to such superinfection remain unclear. here we tested long-term nonprogressors' (ltnps') susceptibility to superinfection using indian rhesus macaques that express the major histocompatibility complex class i (mhc-i) allele mamu-b 17, which is associ ... | 2010 | 20962091 |
| enteric pathology and salmonella-induced cell death in healthy and siv-infected rhesus macaques. | the goal of this study was to morphologically characterize a ligated ileal loop model of salmonella enterica serotype typhimurium infection in rhesus macaques (macaca mulatta) and to verify the occurrence of salmonella-induced cell death in vivo. eight adult healthy male rhesus macaques were used for ligated ileal loop surgery. four macaques had been intravenously inoculated with simian immunodeficiency virus (siv) mac251. ileal ligated loops were inoculated with wild-type (wt) s. typhimurium st ... | 2010 | 21041540 |
| robust vaccine-elicited cellular immune responses in breast milk following systemic simian immunodeficiency virus dna prime and live virus vector boost vaccination of lactating rhesus monkeys. | breast milk transmission of hiv remains an important mode of infant hiv acquisition. enhancement of mucosal hiv-specific immune responses in milk of hiv-infected mothers through vaccination may reduce milk virus load or protect against virus transmission in the infant gastrointestinal tract. however, the ability of hiv/siv strategies to induce virus-specific immune responses in milk has not been studied. in this study, five uninfected, hormone-induced lactating, mamu a*01(+) female rhesus monkey ... | 2010 | 21041730 |
| broadening of cd8+ cell responses in vaccine-based simian immunodeficiency virus controllers. | in our prior study on a prophylactic t-cell-based vaccine, some vaccinated macaques controlled a simian immunodeficiency virus (siv) challenge. these animals allowed viremia in the acute phase but showed persistent viral control after the setpoint. here, we examined the breadth of postchallenge virus-specific cellular immune responses in these siv controllers. | 2010 | 21045637 |
| increased b7-h1 expression on dendritic cells correlates with programmed death 1 expression on t cells in simian immunodeficiency virus-infected macaques and may contribute to t cell dysfunction and disease progression. | suppression of dendritic cell (dc) function in hiv-1 infection is thought to contribute to inhibition of immune responses and disease progression, but the mechanism of this suppression remains undetermined. using the rhesus macaque model, we show b7-h1 (programmed death [pd]-l1) is expressed on lymphoid and mucosal dcs (both myeloid dcs and plasmacytoid dcs), and its expression significantly increases after siv infection. meanwhile, its receptor, pd-1, is upregulated on t cells in both periphera ... | 2010 | 21059890 |
| genomic analysis reveals pre- and postchallenge differences in a rhesus macaque aids vaccine trial: insights into mechanisms of vaccine efficacy. | we have employed global transcriptional profiling of whole blood to identify biologically relevant changes in cellular gene expression in response to alternative aids vaccine strategies with subsequent viral challenge in a rhesus macaque vaccine model. samples were taken at day 0 (prechallenge), day 14 (peak viremia), and week 12 (set point) from animals immunized with replicating adenovirus type 5 host range (ad5hr) recombinant viruses expressing human immunodeficiency virus hiv(env)(89.6p), si ... | 2010 | 21068249 |
| vaccine-induced t cells provide partial protection against high-dose rectal sivmac239 challenge of rhesus macaques. | despite enormous efforts by the scientific community, an effective hiv vaccine remains elusive. to further address to what degree t cells in absence of antibodies may protect against simian immunodeficiency virus (siv) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived ad vector (adc) serotype 6 and then boosted intramuscularly with a serologically distinct adc vector of serotype 7 both expressing gag of sivmac239. animals were subsequently boosted int ... | 2010 | 21081905 |
| early short-term antiretroviral therapy is associated with a reduced prevalence of cd8(+)foxp3(+) t cells in simian immunodeficiency virus-infected controller rhesus macaques. | regulatory t cells contain a mix of cd4 and cd8 t cell subsets that can suppress immune activation and at the same time suppress immune responses, thereby contributing to disease progression. recent studies have shown that an increased prevalence of cd8(+)foxp3(+) t regulatory cells was associated with immune suppression and diminished viral control in simian immunodeficiency virus (siv)-infected rhesus macaques. preventing an increase in the prevalence of cd8 t regulatory subsets is likely to l ... | 2011 | 21142402 |
| loss of il-17-producing cd8 t cells during late chronic stage of pathogenic simian immunodeficiency virus infection. | progressive disease caused by pathogenic siv/hiv infections is marked by systemic hyperimmune activation, immune dysregulation, and profound depletion of cd4(+) t cells in lymphoid and gastrointestinal mucosal tissues. il-17 is important for protective immunity against extracellular bacterial infections at mucosa and for maintenance of mucosal barrier. although il-17-secreting cd4 (th17) and cd8 (tc17) t cells have been reported, very little is known about the latter subset for any infectious di ... | 2010 | 21148794 |
| blocking of α4β7 gut-homing integrin during acute infection leads to decreased plasma and gastrointestinal tissue viral loads in simian immunodeficiency virus-infected rhesus macaques. | intravenous administration of a novel recombinant rhesus mab against the α4β7 gut-homing integrin (mab) into rhesus macaques just prior to and during acute siv infection resulted in significant decrease in plasma and gastrointestinal (gi) tissue viral load and a marked reduction in gi tissue proviral dna load as compared with control siv-infected rhesus macaques. this mab administration was associated with increases in peripheral blood naive and central memory cd4(+) t cells and maintenance of a ... | 2010 | 21149598 |
| distinct host cell proteins incorporated by siv replicating in cd4+ t cells from natural disease resistant versus non-natural disease susceptible hosts. | enveloped viruses including the simian immunodeficiency virus (siv) replicating within host cells acquire host proteins upon egress from the host cells. a number of studies have catalogued such host proteins, and a few have documented the potential positive and negative biological functions of such host proteins. the studies conducted herein utilized proteomic analysis to identify differences in the spectrum of host proteins acquired by a single source of siv replicating within cd4+ t cells from ... | 2010 | 21162735 |
| persistence of gut mucosal innate immune defenses by enteric α-defensin expression in the simian immunodeficiency virus model of aids. | gastrointestinal mucosa is an early target of hiv and a site of viral replication and severe cd4(+) t cell depletion. however, effects of hiv infection on gut mucosal innate immune defense have not been fully investigated. intestinal paneth cell-derived α-defensins constitute an integral part of the gut mucosal innate defense against microbial pathogens. using the siv-infected rhesus macaque model of aids, we examined the level of expression of rhesus enteric α-defensins (reds) in the jejunal mu ... | 2010 | 21178012 |
| correlation between cd4+ t-cell loss and gag-specific t cells in different intestinal sites of chronically siv-infected rhesus monkeys. | to determine the loss of cd4+ t cells and virus-specific cytotoxic t cells (ctl) in different mucosal sites of rhesus monkeys infected with simian immunodeficiency virus (siv). | 2011 | 21192228 |
| myocarditis in cd8-depleted siv-infected rhesus macaques after short-term dual therapy with nucleoside and nucleotide reverse transcriptase inhibitors. | although highly active antiretroviral therapy (haart) has dramatically reduced the morbidity and mortality associated with hiv infection, a number of antiretroviral toxicities have been described, including myocardial toxicity resulting from the use of nucleotide and nucleoside reverse transcriptase inhibitors (nrtis). current treatment guidelines recommend the use of haart regimens containing two nrtis for initial therapy of hiv-1 positive individuals; however, potential cardiotoxicity resultin ... | 2010 | 21203448 |
| early myeloid dendritic cell dysregulation is predictive of disease progression in simian immunodeficiency virus infection. | myeloid dendritic cells (mdc) are lost from blood in individuals with human immunodeficiency virus (hiv) infection but the mechanism for this loss and its relationship to disease progression are not known. we studied the mdc response in blood and lymph nodes of simian immunodeficiency virus (siv)-infected rhesus macaques with different disease outcomes. early changes in blood mdc number were inversely correlated with virus load and reflective of eventual disease outcome, as animals with stable i ... | 2010 | 21203477 |
| simian immunodeficiency virus sivmac239deltanef vaccination elicits different tat28-35sl8-specific cd8+ t-cell clonotypes compared to a dna prime/adenovirus type 5 boost regimen in rhesus macaques. | different human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) vaccine vectors expressing the same viral antigens can elicit disparate t-cell responses. within this spectrum, replicating variable vaccines, like sivmac239?nef, appear to generate particularly efficacious cd8(+) t-cell responses. here, we sequenced t-cell receptor ß-chain (trb) gene rearrangements from immunodominant mamu-a 01-restricted tat(28-35)sl8-specific cd8(+) t-cell populations together with the correspond ... | 2011 | 21270159 |
| functional analysis of frequently expressed chinese rhesus macaque mhc class i molecules mamu-a1*02601 and mamu-b*08301 reveals hla-a2 and hla-a3 supertypic specificities. | the simian immunodeficiency virus (siv)-infected indian rhesus macaque (macaca mulatta) is the most established model of hiv infection and aids-related research, despite the potential that macaques of chinese origin is a more relevant model. ongoing efforts to further characterize the chinese rhesus macaques' major histocompatibility complex (mhc) for composition and function should facilitate greater utilization of the species. previous studies have demonstrated that chinese-origin m. mulatta ( ... | 2011 | 21274527 |
| double-positive cd21+cd27+ b cells are highly proliferating memory cells and their distribution differs in mucosal and peripheral tissues. | several b-cell defects arise in hiv infected patients, particularly in patients with chronic infection and high viral load. loss of memory b cells (cd27(+) b cells) in peripheral blood and lymphoid tissues is one of the major b cell dysfunctions in hiv and simian immunodeficiency virus (siv) infection. despite several studies, definitive identification of memory b cells based on cd27 surface expression has not been described. similarly, the rates of cell turnover in different b cell subpopulatio ... | 2011 | 21304587 |
| epitope-specific cd8+ t lymphocytes cross-recognize mutant simian immunodeficiency virus (siv) sequences but fail to contain very early evolution and eventual fixation of epitope escape mutations during siv infection. | human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) evade containment by cd8(+) t lymphocytes through focused epitope mutations. however, because of limitations in the numbers of viral sequences that can be sampled, traditional sequencing technologies have not provided a true representation of the plasticity of these viruses or the intensity of cd8(+) t lymphocyte-mediated selection pressure. moreover, the strategy by which cd8(+) t lymphocytes contain evolving viral quasi ... | 2011 | 21307185 |
| cryptosporidiosis in rhesus macaques challenged during acute and chronic phases of siv infection. | abstract the intestinal immune dysfunction due to loss of mucosal and peripheral cd4(+) t cells in individuals with hiv/aids is presumably responsible for the establishment of persistent cryptosporidiosis. simian immunodeficiency virus (siv)-infected macaques were used to investigate the phase/timing in siv infection, which permits a self-limiting cryptosporidium parvum infection to become persistent in immunodeficient hosts because of significant mucosal immune defects. two groups of siv-infect ... | 2011 | 21314434 |
| long-term control of simian immunodeficiency virus mac251 viremia to undetectable levels in half of infected female rhesus macaques nasally vaccinated with simian immunodeficiency virus dna/recombinant modified vaccinia virus ankara. | the efficacy of two siv dna plus recombinant modified vaccinia virus ankara nasal vaccine regimens, one combined with plasmids expressing il-2 and il-15, the other with plasmids expressing gm-csf, il-12, and tnf-a, which may better stimulate humoral responses, was evaluated in two female rhesus macaque groups. vaccination stimulated significant siv-specific mucosal and systemic cell-mediated immunity in both groups, whereas siv-specific iga titers were sporadic and igg titers negative. all vacci ... | 2011 | 21317390 |
| characterization and allelic polymorphisms of rhesus macaque (macaca mulatta) igg fc receptor genes. | macaque models are invaluable for aids research. indeed, initial development of hiv-1 vaccines relies heavily on simian immunodeficiency virus-infected rhesus macaques. neutralizing antibodies, a major component of anti-hiv protective responses, ultimately interact with fc receptors on phagocytic and natural killer cells to eliminate the pathogen. despite the major role that fc receptors play in protective responses, there is very limited information available on these molecules in rhesus macaqu ... | 2011 | 21327607 |
| topical nonnucleoside reverse transcriptase inhibitor mc 1220 partially prevents vaginal rt-shiv infection of macaques. | abstract the availability of an effective vaginal microbicide would be a major step toward containment of hiv transmission as well as allowing women self-protection against hiv infection. here we evaluated the efficacy of vaginal application of the potent nonnucleoside reverse transcriptase inhibitor (nnrti) mc 1220 against vaginal challenge of macaques with rt-shiv, a chimeric simian immunodeficiency virus (siv) containing the reverse transcriptase (rt) gene of hiv-1. challenge infection of mon ... | 2011 | 21332419 |
| use of lectins in affinity purification of hiv and siv envelope glycoproteins. | the human immunodeficiency viruses (hiv-1 and hiv-2) are the etiologic agents of the acquired immunodeficiency syndrome (aids) and related disorders (1-3) simian immunodeficiency virus(siv) is the corresponding virus for nonhuman primates. sivmac has been isolated from rhesus monkeys (macaca mulatta) with immunosuppression and malignant lymphomas (4). | 1998 | 21374468 |
| genital tract sequestration of siv following acute infection. | we characterized the evolution of simian immunodeficiency virus (siv) in the male genital tract by examining blood- and semen-associated virus from experimentally and sham vaccinated rhesus monkeys during primary infection. at the time of peak virus replication, siv sequences were intermixed between the blood and semen supporting a scenario of high-level virus "spillover" into the male genital tract. however, at the time of virus set point, compartmentalization was apparent in 4 of 7 evaluated m ... | 2011 | 21379569 |
| ulcerative cheilitis in a rhesus macaque. | a 2-year-old, female, simian immunodeficiency virus e543-infected rhesus macaque (macaca mulatta) was presented for necropsy following euthanasia due to a history of diarrhea, weight loss, and a small, round ulcer along the left labial commissure. histopathologic examination of the ulcer revealed infiltration by large numbers of degenerate and nondegenerate neutrophils and macrophages admixed with syncytial epithelial cells. rare epithelial cells contained herpetic inclusion bodies. these cells ... | 2011 | 21383117 |
| specific pathogen-free status alters immunophenotype in rhesus macaques: implications for the study of simian immunodeficiency virus. | abstract the repertoire of viruses to which research primates are exposed, even in the absence of clinical disease, may contribute to experimental confounding. in this study we examined whether standard specific pathogen-free (spf) rhesus macaques exposed to a wider spectrum of enzootic viruses and expanded spf macaques derived to exclude a greater number of viral agents would display alterations in immune activation or immune cell populations. given the impact of immunophenotype on human immuno ... | 2011 | 21391843 |
| the nonnucleoside reverse transcriptase inhibitor miv-150 in carrageenan gel prevents rectal transmission of simian/human immunodeficiency virus infection in macaques. | development of a microbicide that prevents rectal transmission of human immunodeficiency virus (hiv) is a vital component in reducing hiv spread. we recently demonstrated that a formulation of the nonnucleoside reverse transcriptase inhibitor (nnrti) miv-150 in carrageenan reduced vaginal infection of macaques with simian immunodeficiency virus sivmac239 with hiv-1(hxb2) reverse transcriptase (shiv-rt). herein, we performed the first testing of miv-150-carrageenan against rectal infection. rhesu ... | 2011 | 21411526 |
| morphine potentiates neuropathogenesis of siv infection in rhesus macaques. | despite the advent of antiretroviral therapy, complications of hiv-1 infection with concurrent drug abuse are an emerging problem. opiates are well known to modulate immune responses by preventing the development of cell-mediated immune responses. their effect on the pathogenesis of hiv-1 infection however remains controversial. using the simian immunodeficiency virus/macaque model of hiv pathogenesis, we sought to explore the impact of morphine on disease progression and pathogenesis. sixteen r ... | 2011 | 21431470 |
| early induction of polyfunctional simian immunodeficiency virus (siv)-specific t lymphocytes and rapid disappearance of siv from lymph nodes of sooty mangabeys during primary infection. | although the cellular immune response is essential for controlling siv replication in asian macaques, its role in maintaining nonpathogenic siv infection in natural hosts such as sooty mangabeys (sm) remains to be defined. we have previously shown that similar to rhesus macaques (rm), sm are able to mount a t lymphocyte response against siv infection. to investigate early control of siv replication in natural hosts, we performed a detailed characterization of siv-specific cellular immunity and v ... | 2011 | 21441446 |
| antibody-dependent cell-mediated viral inhibition emerges after simian immunodeficiency virus sivmac251 infection of rhesus monkeys coincident with gp140-binding antibodies and is effective against neutralization-resistant viruses. | antibody-dependent cell-mediated viral inhibition (adcvi) is an attractive target for vaccination because it takes advantage of both the anamnestic properties of an adaptive immune response and the rapid early response characteristics of an innate immune response. effective utilization of adcvi in vaccine strategies will depend on an understanding of the natural history of adcvi during acute and chronic human immunodeficiency virus type 1 (hiv-1) infection. we used the simian immunodeficiency vi ... | 2011 | 21450829 |
| tolerance to chronic delta-9-tetrahydrocannabinol (δ⁹-thc) in rhesus macaques infected with simian immunodeficiency virus. | although δ⁹-thc has been approved to treat anorexia and weight loss associated with aids, it may also reduce well-being by disrupting complex behavioral processes or enhancing hiv replication. to investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or δ⁹-thc before and after inoculation with simian immunodeficiency virus (siv(mac251), 100 tcid₅₀/ml, i.v.). prior to chronic δ⁹- ... | 2011 | 21463073 |
| cd8(+) lymphocyte depletion without siv infection does not produce metabolic changes or pathological abnormalities in the rhesus macaque brain. | background simian immunodeficiency virus (siv) infection and persistent cd8(+) lymphocyte depletion rapidly leads to encephalitis and neuronal injury. the objective of this study is to confirm that cd8 depletion alone does not induce brain lesions in the absence of siv infection. methods four rhesus macaques were monitored by proton magnetic resonance spectroscopy ((1) h-mrs) before and biweekly after anti-cd8 antibody treatment for 8 weeks and compared with four siv-infected animals. post-mor ... | 2011 | 21463330 |
| chronic δ-9-tetrahydrocannabinol administration increases lymphocyte cxcr4 expression in rhesus macaques. | cannabinoids have been reported to produce various immunomodulatory effects, which could potentially impact the host response to bacterial or viral infection. we have recently demonstrated that chronic δ-9-tetrahydrocannabinol (thc; 0.32 mg/kg i.m., bid) decreased early mortality in rhesus macaques infected with simian immunodeficiency virus (siv). however, the possibility that prolonged thc administration affects lymphocyte counts, phenotype, and proliferation indices has not been addressed. we ... | 2011 | 21484257 |
| immunization with recombinant hla class i and ii, hiv-1 gp140 and siv p27 elicits protection against heterologous shiv infection in rhesus macaques. | mhc molecules expressed on the surface of hiv are potential targets for neutralising antibodies. since mhc molecules are polymorphic non-self mhc can also be immunogenic. we have used combinations of novel recombinant hla class i and ii and hiv/siv antigens, all linked to dextran, to investigate if they can elicit protective immunity against heterologous shiv challenge in rhesus macaques. three groups of animals were immunized with hla (group 1, n=8), trimeric yu2 hiv-1 gp140 and siv p27 (hiv/si ... | 2011 | 21490092 |
| significant protection against high-dose simian immunodeficiency virus challenge conferred by a new prime-boost vaccine regimen. | we constructed vaccine vectors based on live recombinant vesicular stomatitis virus (vsv) and a semliki forest virus (sfv) replicon (sfvg) that propagates through expression of the vsv glycoprotein (g). these vectors expressing simian immunodeficiency virus (siv) gag and env proteins were used to vaccinate rhesus macaques with a new heterologous prime-boost regimen designed to optimize induction of antibody. six vaccinated animals and six controls were then given a high-dose mucosal challenge wi ... | 2011 | 21490100 |
| significant genetic heterogeneity of the sivmac251 viral swarm derived from different sources. | infecting rhesus macaques (macaca mulatta) with the simian immunodeficiency virus (siv) is an established animal model of human immunodeficiency virus (hiv) pathogenesis. many studies have used various derivatives of the sivmac251 viral swarm to investigate several aspects of the disease, including transmission, progression, response to vaccination and siv/hiv associated neurological disorders. however, the lack of standardization of the infecting inoculum complicates comparative analyses. we in ... | 2011 | 21524235 |
| dominant induction of vaccine antigen-specific cytotoxic t lymphocyte responses after simian immunodeficiency virus challenge. | cytotoxic t lymphocyte (ctl) responses are crucial for the control of human and simian immunodeficiency virus (hiv and siv) replication. a promising aids vaccine strategy is to induce ctl memory resulting in more effective ctl responses post-viral exposure compared to those in natural hiv infections. we previously developed a ctl-inducing vaccine and showed siv control in some vaccinated rhesus macaques. these vaccine-based siv controllers elicited vaccine antigen-specific ctl responses dominant ... | 2011 | 21531211 |
| extended safety and efficacy studies of a live attenuated double leucine and pantothenate auxotroph of mycobacterium tuberculosis as a vaccine candidate. | we have previously described the development of a live, fully attenuated mycobacterium tuberculosis (mtb) vaccine candidate strain with two independent attenuating auxotrophic mutations in leucine and pantothenate biosynthesis. in the present work, those studies have been extended to include testing for protective efficacy in a long-term guinea pig survival model and safety testing in the highly tuberculosis susceptible rhesus macaque. to model the safety of the δleud δpancd strain in hiv-infect ... | 2011 | 21549795 |
| diverse peptide presentation of rhesus macaque mhc class i mamu-a*02 revealed by two peptide-complex structures and insights into siv immune escape. | mhc class i (mhc i)-restricted cd8(+) t-cell responses play a pivotal role in anti-hiv immunity and the control of viremia. rhesus macaque is an important animal model for hiv-related research. among the mhc i alleles of rhesus macaque, mamu-a*02 is prevalent, presenting in ≥ 20% of macaques. in this study, we determined the crystal structure of mamu-a*02, the second structure-determined mhc i from rhesus macaque after mamu-a*01. the peptide presentation characteristics of mamu-a*02 are exhibite ... | 2011 | 21561910 |