Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
|---|
| no evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys. | defining the immune correlates of the protection against human immunodeficiency virus type 1 (hiv-1) acquisition in individuals who are exposed to hiv-1 but do not become infected may provide important direction for the creation of an hiv-1 vaccine. we have employed the simian immunodeficiency virus (siv)/rhesus monkey model to determine whether monkeys can be repeatedly exposed to a primate lentivirus by a mucosal route and escape infection and whether virus-specific immune correlates of protec ... | 2007 | 17686853 |
| early establishment and antigen dependence of simian immunodeficiency virus-specific cd8+ t-cell defects. | differentiation and survival defects of human immunodeficiency virus (hiv)-specific cd8(+) t cells may contribute to the failure of hiv-specific cd8(+) t cells to control hiv replication. it is not known, however, whether simian immunodeficiency virus (siv)-infected rhesus macaques show comparable defects in these virus-specific cd8(+) t cells or when such defects are established during infection. peripheral blood cells from acutely and chronically infected rhesus macaques were stained ex vivo f ... | 2007 | 17670818 |
| simian immunodeficiency virus infection induces severe loss of intestinal central memory t cells which impairs cd4+ t-cell restoration during antiretroviral therapy. | simian immunodeficiency virus (siv) infection leads to severe loss of intestinal cd4(+) t cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (art). mechanisms for this delay have not been examined in context of which specific cd4(+) memory subsets or lost and fail to regenerate during art. | 2007 | 17669210 |
| molecular typing of major histocompatibility complex class i alleles in the indian rhesus macaque which restrict siv cd8+ t cell epitopes. | the utility of the rhesus macaque as an animal model in both hiv vaccine development and pathogenesis studies necessitates the development of accurate and efficient major histocompatibility complex (mhc) genotyping technologies. in this paper, we describe the development and application of allele-specific polymerase chain reaction (pcr) amplification for the simultaneous detection of eight mhc class i alleles from the rhesus macaque (macaca mulatta) of indian descent. these alleles were selected ... | 2007 | 17641886 |
| tgf-beta in intestinal lymphoid organs contributes to the death of armed effector cd8 t cells and is associated with the absence of virus containment in rhesus macaques infected with the simian immunodeficiency virus. | siv-infected macaques exhibit distinct rates of progression to aids and despite significant increases in cd8+ t cells, immune cells fail to control and eradicate siv in vivo. here, we investigated the interplay between viral reservoir sites, cd8+ t-cell activation/death and outcome. our data provide strong evidence that mesenteric (mes) lymph nodes represent major reservoirs not only for siv-infected macaques progressing more rapidly toward aids but also in controllers. we demonstrate that macaq ... | 2007 | 17612589 |
| post-infection immunodeficiency virus control by neutralizing antibodies. | unlike most acute viral infections controlled with the appearance of virus-specific neutralizing antibodies (nabs), primary hiv infections are not met with such potent and early antibody responses. this brings into question if or how the presence of potent antibodies can contribute to primary hiv control, but protective efficacies of antiviral antibodies in primary hiv infections have remained elusive; and, it has been speculated that even nab induction could have only a limited suppressive effe ... | 2007 | 17579714 |
| hiv/aids: in search of an animal model. | aids is among the most devastating diseases of our time, claiming the lives of approximately 3 million people per year. the primary cause of aids, human immunodeficiency virus type 1 (hiv-1), is a pathogen that is highly specific for humans and generally does not infect or cause disease in other species. this property complicates the generation of animal models that are urgently needed to test new antiretroviral therapies and vaccines. the most practical animal models developed to date consist o ... | 2007 | 17574286 |
| the central nervous system in mucosal vaccination of rhesus macaques with simian immunodeficiency virus deltanef. | we studied the central nervous system (cns) of rhesus macaques during series of vaccination experiments in which attenuated simian immunodeficiency virus (siv), sivmac239deltanef, was applied to the tonsils and the animals were later challenged with pathogenic sivmac251 or shiv/89.6p via tonsils or rectum. the pathologic lesions were graded on a scale of 0-5. the lesions were in general very mild, with a score of 0.5, except for one case, in which the animal had progressed to simian aids (saids) ... | 2007 | 17573813 |
| heterologous prime/boost immunization of rhesus monkeys by using diverse poxvirus vectors. | as the diversity of potential immunogens increases within certain classes of vectors, the possibility has arisen of employing heterologous prime/boost immunizations using diverse members of the same family of vectors. the present study was initiated to explore the use of divergent pox vectors in a prime/boost regimen to elicit high-frequency cellular immune responses to human immunodeficiency virus type 1 envelope and simian immunodeficiency virus gag in rhesus monkeys. we demonstrated that monk ... | 2007 | 17553898 |
| depletion of cd8+ cells in sooty mangabey monkeys naturally infected with simian immunodeficiency virus reveals limited role for immune control of virus replication in a natural host species. | siv infection of sooty mangabeys (sms), a natural host species, does not cause aids despite high-level virus replication. in contrast, siv infection of nonnatural hosts such as rhesus macaques (rms) induces an aids-like disease. the depletion of cd8+ t cells during siv infection of rms results in marked increases in plasma viremia, suggesting a key role for cd8+ t cells in controlling levels of siv replication. to assess the role that cd8+ t cells play in determining the virologic and immunologi ... | 2007 | 17548637 |
| cd4+ t cells from simian immunodeficiency virus disease-resistant sooty mangabeys produce more il-2 than cells from disease-susceptible species: involvement of p300 and creb at the proximal il-2 promoter in il-2 up-regulation. | il-2 is an important cytokine required for the physiological function of cd4(+) t cells. immunological unresponsiveness-anergy- of cd4(+) t cells is characterized by the inability of these cells to synthesize il-2. both progressive hiv infection leading to aids in humans and siv infection in rhesus macaques (rm) are associated with dysregulation of il-2 synthesis. in certain nonhuman primate species, such as sooty mangabeys (sm), siv infection does not lead to aids. we have shown that this is as ... | 2007 | 17548609 |
| mamu-b*08-positive macaques control simian immunodeficiency virus replication. | certain major histocompatibility complex (mhc) class i alleles are associated with the control of human immunodeficiency virus and simian immunodeficiency virus (siv) replication. we have designed sequence-specific primers for detection of the rhesus macaque mhc class i allele mamu-b*08 by pcr and screened a cohort of siv-infected macaques for this allele. analysis of 196 siv(mac)239-infected indian rhesus macaques revealed that mamu-b*08 was significantly overrepresented in elite controllers; 3 ... | 2007 | 17537848 |
| vif counteracts a cyclophilin a-imposed inhibition of simian immunodeficiency viruses in human cells. | vif is a primate lentiviral accessory protein that is crucial for viral infectivity. vif counteracts the antiviral activity of host deaminases such as apobec3g and apobec3f. we now report a novel function of african green monkey simian immunodeficiency virus (sivagm) vif that promotes replication of sivagm in human cells lacking detectable deaminase activity. we found that cyclophilin a (cypa) was excluded from wild-type siv particles but was efficiently packaged into vif-deficient sivagm virion ... | 2007 | 17522232 |
| memory cd4+ t-lymphocyte loss and dysfunction during primary simian immunodeficiency virus infection. | it has long been appreciated that cd4+ t lymphocytes are dysfunctional in human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv)-infected individuals, and it has recently been shown that hiv/siv infections are associated with a dramatic early destruction of memory cd4+ t lymphocytes. however, the relative contributions of cd4+ t-lymphocyte dysfunction and loss to immune dysregulation during primary hiv/siv infection have not been fully elucidated. in the current study, we evaluat ... | 2007 | 17522197 |
| human and simian immunodeficiency virus-mediated upregulation of the apoptotic factor trail occurs in antigen-presenting cells from aids-susceptible but not from aids-resistant species. | human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) infections lead to aids in humans and rhesus macaques (rm), while they are asymptomatic in species naturally infected with siv, such as chimpanzees, sooty mangabeys (sm), and african green monkeys (agm). differential cd4(+) t-cell apoptosis may be responsible for these species-specific differences in susceptibility to disease. to identify factors that influence the different apoptotic responses of these species, we analyz ... | 2007 | 17494085 |
| mucosal innate immune response associated with a timely humoral immune response and slower disease progression after oral transmission of simian immunodeficiency virus to rhesus macaques. | mucosal transmission is the predominant mode of human immunodeficiency virus (hiv) infection worldwide, and the mucosal innate interferon response represents an important component of the earliest host response to the infection. our goal here was to assess the changes in mrna expression of innate mucosal genes after oral simian immunodeficiency virus (siv) inoculation of rhesus macaques (macaca mulatta) that were followed throughout their course of disease progression. the siv plasma viral load ... | 2007 | 17428863 |
| immunogenicity of hybrid dna vaccines expressing hepatitis b core particles carrying human and simian immunodeficiency virus epitopes in mice and rhesus macaques. | an effective hiv vaccine will likely need to induce broad and potent ctl responses. epitope-based vaccines offer significant potential for inducing multi-specific ctl, but often require conjugation to t helper epitopes or carrier moieties to induce significant responses. we tested hybrid dna vaccines encoding one or more hiv or siv ctl epitopes fused to a hepatitis b core antigen (hbcag) carrier gene as a means to improve the immunogenicity of epitope-based dna vaccines. immunization of mice wit ... | 2007 | 17428516 |
| sequential emergence and clinical implications of viral mutants with k70e and k65r mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic rt-shiv infection. | we reported previously on the emergence and clinical implications of simian immunodeficiency virus (sivmac251) mutants with a k65r mutation in reverse transcriptase (rt), and the role of cd8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. because of significant sequence differences between siv and hiv-1 rt that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with siv can be extrapolated to hiv-1 rt. accordingly, to mode ... | 2007 | 17417971 |
| enteric ganglionitis in rhesus macaques infected with simian immunodeficiency virus. | gastrointestinal (gi) disease is a debilitating feature of human immunodeficiency virus (hiv) infection that can occur in the absence of histopathological abnormalities or identifiable enteropathogens. however, the mechanisms of gi dysfunction are poorly understood. the present study was undertaken to characterize changes in resident and inflammatory cells in the enteric nervous system (ens) of macaques during the acute stage of simian immunodeficiency virus (siv) infection to gain insight into ... | 2007 | 17392357 |
| unique pathology in simian immunodeficiency virus-infected rapid progressor macaques is consistent with a pathogenesis distinct from that of classical aids. | simian immunodeficiency virus (siv) infection of macaques and human immunodeficiency virus type 1 (hiv-1) infection of humans result in variable but generally fatal disease outcomes. most siv-infected macaques progress to aids over a period of 1 to 3 years, in the face of robust siv-specific immune responses (conventional progressors [cp]). a small number of siv-inoculated macaques mount transient immune responses and progress rapidly to aids (rapid progressors [rp]). we speculated that the unde ... | 2007 | 17376901 |
| therapeutic immunization with modified vaccinia virus ankara (mva) vaccines in siv-infected rhesus monkeys undergoing antiretroviral therapy. | the long-term benefits of highly active antiretroviral therapy in hiv-infected patients are limited by emergence of drug-resistant variants and side effects. therefore, we studied the concept of therapeutic immunization in 18 rhesus monkeys infected with a highly pathogenic simian immunodeficiency virus (siv) swarm. | 2007 | 17359459 |
| long-term control of simian immunodeficiency virus replication with central memory cd4+ t-cell preservation after nonsterile protection by a cytotoxic t-lymphocyte-based vaccine. | induction of virus-specific cd8(+) cytotoxic t-lymphocyte (ctl) responses is a promising strategy for aids vaccine development. however, it has remained unclear if or how long-term viral containment and disease control are attainable by ctl-based nonsterile protection. here, we present three rhesus macaques that successfully maintained env-independent vaccine-based control of simian immunodeficiency virus (siv) mac239 replication without disease progression for more than 3 years. siv-specific ne ... | 2007 | 17344296 |
| interleukin-15 but not interleukin-7 abrogates vaccine-induced decrease in virus level in simian immunodeficiency virus mac251-infected macaques. | the loss of cd4(+) t cells and the impairment of cd8(+) t cell function in hiv infection suggest that pharmacological treatment with il-7 and il-15, cytokines that increase the homeostatic proliferation of t cells and improve effector function, may be beneficial. however, these cytokines could also have a detrimental effect in hiv-1-infected individuals, because both cytokines increase hiv replication in vitro. we assessed the impact of il-7 and il-15 treatment on viral replication and the immun ... | 2007 | 17339444 |
| analysis of tcralphabeta combinations used by simian immunodeficiency virus-specific cd8+ t cells in rhesus monkeys: implications for ctl immunodominance. | immunodominance is a common feature of ag-specific ctl responses to infection or vaccines. understanding the basis of immunodominance is crucial to understanding cellular immunity and viral evasion mechanisms and will provide a rational approach for improving hiv vaccine design. this study was performed comparing ctls specific for the siv gag p11c (dominant) and siv pol p68a (subdominant) epitopes that are consistently generated in mamu-a*01(+) rhesus monkeys exposed to siv proteins. additionall ... | 2007 | 17339435 |
| understanding and exploiting dendritic cells in human immunodeficiency virus infection using the nonhuman primate model. | dendritic cells (dc) are pivotal cells in the innate immune system. recent interest in the role of dc in human immunodeficiency virus (hiv) pathogenesis has increased with the finding that both myeloid (mdc) and plasmacytoid dc (pdc) are lost from blood during infection, associated with progression to disease. dc are also being studied intensively for their capacity to stimulate robust virus-specific immunity as vaccines. here we discuss our work in these contrasting fields of dc biology using t ... | 2006 | 17337787 |
| highly attenuated rabies virus-based vaccine vectors expressing simian-human immunodeficiency virus89.6p env and simian immunodeficiency virusmac239 gag are safe in rhesus macaques and protect from an aids-like disease. | we analyzed the safety and immunogenicity of attenuated rabies virus vectors expressing simian-human immunodeficiency virus (shiv)-1(89.6p) env or simian immunodeficiency virus (siv)(mac239) gag in rhesus macaques. four test macaques were immunized with both vaccine constructs, and 2 control macaques received an empty rabies vector. seroconversion against rabies virus glycoprotein (g) and shiv(89.6p) env was detected after the initial immunization, but no cellular responses against shiv antigens ... | 2007 | 17330788 |
| antiviral antibodies are necessary for control of simian immunodeficiency virus replication. | to better define the role of b cells in the control of pathogenic simian immunodeficiency virus (siv) replication, six rhesus monkeys were depleted of b cells by intravenous infusion of rituximab (anti-cd20) 28 days and 7 days before intravaginal sivmac239 inoculation and every 21 days thereafter until aids developed. although the blood and tissues were similarly depleted of b cells, anti-siv immunoglobulin g (igg) antibody responses were completely blocked in only three of the six animals. in a ... | 2007 | 17329327 |
| growth regulation of simian and human aids-related non-hodgkin's lymphoma cell lines by tgf-beta1 and il-6. | aids-related non-hodgkin's lymphoma (aids-nhl) is the second most frequent cancer associated with aids, and is a frequent cause of death in hiv-infected individuals. experimental analysis of aids-nhl has been facilitated by the availability of an excellent animal model, i.e., simian acquired immunodeficiency syndrome (saids) in the rhesus macaque consequent to infection with simian immunodeficiency virus. a recent study of saids-nhl demonstrated a lymphoma-derived cell line to be sensitive to th ... | 2007 | 17324269 |
| simian immunodeficiency virus (siv) infection influences the level and function of regulatory t cells in siv-infected rhesus macaques but not siv-infected sooty mangabeys. | differences in clinical outcome of simian immunodeficiency virus (siv) infection in disease-resistant african sooty mangabeys (sm) and disease-susceptible asian rhesus macaques (rm) prompted us to examine the role of regulatory t cells (tregs) in these two animal models. results from a cross-sectional study revealed maintenance of the frequency and absolute number of peripheral tregs in chronically siv-infected sm while a significant loss occurred in chronically siv-infected rm compared to uninf ... | 2007 | 17314162 |
| reference strand-mediated conformation analysis-based typing of multiple alleles in the rhesus macaque mhc class i mamu-a and mamu-b loci. | the rhesus macaque exhibits individual differences in susceptibility and resistance to infectious agents such as simian immunodeficiency virus (siv) under experimental conditions, and these may be genetically determined at least in part by major histocompatibility complex (mhc) class i polymorphism. although the importance of defining mhc class i polymorphism is well recognized, development of a generic and comprehensive molecular typing method of mhc class i alleles of the rhesus macaque has be ... | 2007 | 17309048 |
| single nucleotide polymorphisms (snps) distinguish indian-origin and chinese-origin rhesus macaques (macaca mulatta). | rhesus macaques serve a critical role in the study of human biomedical research. while both indian and chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (siv) infection. single nucleotide polymorphisms (snps) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. we sequenced the 3' end of rhesus ma ... | 2007 | 17286860 |
| vaccine-based, long-term, stable control of simian/human immunodeficiency virus 89.6pd replication in rhesus macaques. | the x4-tropic simian/human immunodeficiency virus (shiv) 89.6p (or 89.6pd) causes rapid cd4(+) t-cell depletion leading to an acute crash of the host immune system, whereas pathogenic r5-tropic simian immunodeficiency virus (siv) infection, like hiv-1 infection in humans, results in chronic disease progression in macaques. recent pre-clinical vaccine trials inducing cytotoxic t lymphocyte (ctl) responses have succeeded in controlling replication of the former but shown difficulty in control of t ... | 2007 | 17251584 |
| subdominant cd8+ t-cell responses are involved in durable control of aids virus replication. | "elite controllers" are individuals that durably control human immunodeficiency virus or simian immunodeficiency virus replication without therapeutic intervention. the study of these rare individuals may facilitate the definition of a successful immune response to immunodeficiency viruses. here we describe six indian-origin rhesus macaques that have controlled replication of the pathogenic virus sivmac239 for 1 to 5 years. to determine which lymphocyte populations were responsible for this cont ... | 2007 | 17251286 |
| human t cell leukemia virus type 1 up-regulation after simian immunodeficiency virus-1 coinfection in the nonhuman primate. | the effects that human t cell leukemia virus (htlv) type 1 and simian immunodeficiency virus (siv) coinfection have on htlv-1 dynamics and disease progression were tested in a nonhuman primate model. seven rhesus macaques were experimentally inoculated with htlv-1, and a persistent infection was established. coinfection with siv/smb670 resulted in increased htlv-1 p19 antigens in peripheral blood mononuclear cells and htlv-1 proviral loads. circulating cd2(+) and cd8(+) t lymphocytes increased o ... | 2007 | 17230416 |
| simian immunodeficiency virus-induced lymphatic tissue fibrosis is mediated by transforming growth factor beta 1-positive regulatory t cells and begins in early infection. | in human immunodeficiency virus (hiv) infection, collagen deposition and fibrosis within the t cell zone disrupt the lymphatic tissue architecture, contributing to depletion of cd4(+) t cells and limiting immune reconstitution. we used relevant animal and in vitro models to investigate the kinetics and possible underlying mechanism(s) of this process. in the lymphatic tissue of simian immunodeficiency virus (siv)-infected rhesus macaques, we observed parallel increases in immune activation, tran ... | 2007 | 17230415 |
| a replication-competent adenovirus-human immunodeficiency virus (ad-hiv) tat and ad-hiv env priming/tat and envelope protein boosting regimen elicits enhanced protective efficacy against simian/human immunodeficiency virus shiv89.6p challenge in rhesus macaques. | we previously demonstrated that replication-competent adenovirus (ad)-simian immunodeficiency virus (siv) recombinant prime/protein boost regimens elicit potent immunogenicity and strong, durable protection of rhesus macaques against siv(mac251). additionally, native tat vaccines have conferred strong protection against simian/human immunodeficiency virus shiv(89.6p) challenge of cynomolgus monkeys, while native, inactivated, or vectored tat vaccines have failed to elicit similar protective effi ... | 2007 | 17229693 |
| genotyping and segregation analyses indicate the presence of only two functional mic genes in rhesus macaques. | mic molecules are stress-inducible ligands of the activating receptor nkg2d, which is expressed on natural killer cells and subsets of t lymphocytes. in rhesus macaques (macaca mulatta), three different mic sequences (mic1, mic2, mic3) have been described that are closely related to but, according to phylogenetic analysis, do not represent orthologues of the human mica and micb genes. although a single haplotype of the rhesus macaque mhc (mamu) has been completely sequenced, it remained unknown ... | 2007 | 17216437 |
| construction of an infectious rhesus rhadinovirus bacterial artificial chromosome for the analysis of kaposi's sarcoma-associated herpesvirus-related disease development. | rhesus rhadinovirus (rrv) is closely related to kaposi's sarcoma-associated herpesvirus (kshv)/human herpesvirus 8 (hhv-8) and causes kshv-like diseases in immunocompromised rhesus macaques (rm) that resemble kshv-associated diseases including multicentric castleman's disease and non-hodgkin's lymphoma. rrv retains a majority of open reading frames (orfs) postulated to be involved in the pathogenesis of kshv and is the closest available animal model to kshv infection in humans. here we describe ... | 2007 | 17215283 |
| differential distribution of antibodies to different viruses in young animals in the free-ranging rhesus macaques of cayo santiago. | the breeding colony of free-ranging rhesus macaques was established in 1938 in cayo santiago (cs) with animals collected in northern india. the seroprevalence to cercopithecine herpesvirus type 1 (b virus) and simian retroviruses has been studied previously. | 2006 | 17214665 |
| simian immunodeficiency virus-induced cd4+ t cell deficits in cytokine secretion profile are dependent on monkey origin. | facets of the immune response early after human immunodeficiency virus (hiv) infection influence the course of disease. in the simian immunodeficiency virus (siv)-rhesus monkey system, a global dysfunction of cd4(+) t cell cytokine secretion was reported to develop early after infection [mckay pf, barouch dh, schmitz je, veazey rs, gorgone da, lifton ma, williams kc, and letvin nl: j virol 2003;77:4695-4702]. because differences have been found in siv pathogenesis depending on the origin of the ... | 2006 | 17201663 |
| tenofovir treatment augments anti-viral immunity against drug-resistant siv challenge in chronically infected rhesus macaques. | emergence of drug-resistant strains of human immunodeficiency virus type 1 (hiv-1) is a major obstacle to successful antiretroviral therapy (art) in hiv-infected patients. whether antiviral immunity can augment art by suppressing replication of drug-resistant hiv-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (siv). rhesus macaques infected with live, attenuated siv develop robust siv-specific immune responses but remain ... | 2006 | 17184540 |
| adaptation of a diverse simian immunodeficiency virus population to a new host is revealed through a systematic approach to identify amino acid sites under selection. | simian immunodeficiency viruses (siv) have had considerable success at crossing species barriers; both human immunodeficiency virus (hiv)-1 and hiv-2 have been transmitted on multiple occasions from siv-infected natural host species. however, the precise evolutionary and ecological mechanisms characterizing a successful cross-species transmission event remain to be elucidated. here, in addition to expanding and clarifying our previous description of the adaptation of a diverse, naturally occurri ... | 2007 | 17159231 |
| fractalkine expression in the rhesus monkey brain during lentivirus infection and its control by 6-chloro-2',3'-dideoxyguanosine. | existing data concerning the role of the delta-chemokine fractalkine (cx3cl1) and its receptor (cx3cr1) in lentivirus-induced encephalitis are limited and controversial. we explored, by quantitative in situ hybridization and immunohistochemistry, the cell-specific changes of cx3cl1 and cx3cr1 in rhesus macaque brain during simian immunodeficiency virus (siv) infection and antiretroviral treatment. neuronal expression of cx3cl1 was significantly reduced in cortex and striatum of aids-diseased mon ... | 2006 | 17146291 |
| long-lasting decrease in viremia in macaques chronically infected with simian immunodeficiency virus sivmac251 after therapeutic dna immunization. | rhesus macaques chronically infected with highly pathogenic simian immunodeficiency virus (siv) sivmac251 were treated with antiretroviral drugs and vaccinated with combinations of dna vectors expressing siv antigens. vaccination during therapy increased cellular immune responses. after the animals were released from therapy, the virus levels of 12 immunized animals were significantly lower (p = 0.001) compared to those of 11 animals treated with only antiretroviral drugs. vaccinated animals sho ... | 2007 | 17135321 |
| a simian immunodeficiency virus v3 loop mutant that does not efficiently use ccr5 or common alternative coreceptors is moderately attenuated in vivo. | sexually transmitted hiv-1 strains utilize the chemokine receptor ccr5 for viral entry and inhibitors targeting this coreceptor offer great promise for antiretroviral therapy. they also raise the question, however, whether viral variants exhibiting altered coreceptor interactions and resistance against these antiviral agents might still be pathogenic. in the present study, we analyzed a sivmac239 envelope (env) mutant (239dl) containing two mutations in the v3 loop which reduced viral entry via ... | 2007 | 17126374 |
| chronic alcohol accentuates nutritional, metabolic, and immune alterations during asymptomatic simian immunodeficiency virus infection. | alcohol abuse has been reported to have a high prevalence in the human immunodeficiency virus (hiv)-infected population. however, its impact on disease progression is unknown. studies dissecting the drug-induced or alcohol-induced metabolic derangements that are likely to alter the course of disease progression are lacking. this is particularly important because of the substantial reduction in morbidity and mortality of patients on highly active antiretroviral therapy (haart). hiv infection has ... | 2006 | 17117972 |
| induction of a virus-specific effector-memory cd4+ t cell response by attenuated siv infection. | we investigated simian immunodeficiency virus (siv)-specific cd4+ t cell responses in rhesus macaques chronically infected with attenuated or pathogenic siv strains. analysis of sivdeltanef-infected animals revealed a relatively high frequency of siv-specific cd4+ t cells representing 4-10% of all cd4+ t lymphocytes directed against multiple siv proteins. gag-specific cd4+ t cells in wild-type siv-infected animals were 5-10-fold lower in frequency and inversely correlated with the level of plasm ... | 2006 | 17116733 |
| microbial translocation is a cause of systemic immune activation in chronic hiv infection. | chronic activation of the immune system is a hallmark of progressive hiv infection and better predicts disease outcome than plasma viral load, yet its etiology remains obscure. here we show that circulating microbial products, probably derived from the gastrointestinal tract, are a cause of hiv-related systemic immune activation. circulating lipopolysaccharide, which we used as an indicator of microbial translocation, was significantly increased in chronically hiv-infected individuals and in sim ... | 2006 | 17115046 |
| loss of naïve cells accompanies memory cd4+ t-cell depletion during long-term progression to aids in simian immunodeficiency virus-infected macaques. | human immunodeficiency virus and simian immunodeficiency virus (siv) induce a slow progressive disease, characterized by the massive loss of memory cd4+ t cells during the acute infection followed by a recovery phase in which virus replication is partially controlled. however, because the initial injury is so severe and virus production persists, the immune system eventually collapses and a symptomatic fatal disease invariably occurs. we have assessed cd4+ t-cell dynamics and disease progression ... | 2007 | 17093193 |
| rhesus monkey rhadinovirus: a model for the study of kshv. | rhesus monkey rhadinovirus (rrv) is one of the closest phylogenetic relatives to the human pathogen kaposi sarcoma-associated herpesvirus (kshv)-a gamma-2 herpesvirus and the etiologic agent of three malignancies associated with immunosuppression. in contrast to kshv, rrv displays robust lytic-phase growth in culture, replicating to high titer, and therefore holds promise as an effective model for studying primate gammaherpesvirus lytic gene transcription as well as virion structure, assembly, a ... | 2007 | 17089793 |
| control of simian immunodeficiency virus sivmac239 is not predicted by inheritance of mamu-b*17-containing haplotypes. | it is well established that host genetics, especially major histocompatibility complex (mhc) genes, are important determinants of human immunodeficiency virus disease progression. studies with simian immunodeficiency virus (siv)-infected indian rhesus macaques have associated mamu-b*17 with control of virus replication. using microsatellite haplotyping of the 5-mb mhc region, we compared disease progression among sivmac239-infected indian rhesus macaques that possess mamu-b*17-containing mhc hap ... | 2007 | 17079280 |
| generation of hiv-1 derivatives that productively infect macaque monkey lymphoid cells. | the narrow host range of human immunodeficiency virus type 1 (hiv-1) is caused in part by innate cellular factors such as apolipoprotein b mrna-editing enzyme-catalytic polypeptide-like 3g (apobec3g) and trim5alpha, which restrict virus replication in monkey cells. variant hiv-1 molecular clones containing both a 21-nucleotide simian immunodeficiency virus (siv) gag ca element, corresponding to the hiv-1 cyclophilin a-binding site, and the entire siv vif gene were constructed. long-term passage ... | 2006 | 17065315 |
| anti-ox40 (cd134) administration to nonhuman primates: immunostimulatory effects and toxicokinetic study. | the immune-stimulatory properties of anti-cd134 (ox40) antibodies have been well documented in rodents, including their ability to enhance antitumor immunity. in this study, an anti-ox40 antibody (ab) known to costimulate monkey t cells in vitro, was infused into rhesus macaque monkeys during immunization with the simian immunodeficiency virus protein, gp130. the draining lymph nodes from immunized monkeys treated with anti-ox40 were enlarged compared with immunized monkeys injected with mouse i ... | 2006 | 17063120 |
| massive infection and loss of cd4+ t cells occurs in the intestinal tract of neonatal rhesus macaques in acute siv infection. | rapid, profound, and selective depletion of memory cd4+ t cells has now been confirmed to occur in simian immunodeficiency virus (siv)-infected adult macaques and human immunodeficiency virus (hiv)-infected humans. within days of infection, marked depletion of memory cd4+ t cells occurs primarily in mucosal tissues, the major reservoir for memory cd4+ t cells in adults. however, hiv infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of me ... | 2007 | 17047153 |
| contribution of t-cell receptor repertoire breadth to the dominance of epitope-specific cd8+ t-lymphocyte responses. | dominant epitope-specific cd8(+) t-lymphocyte responses play a central role in controlling viral spread. we explored the basis for the development of this focused immune response in simian immunodeficiency virus (siv)- and simian-human immunodeficiency virus (shiv)-infected rhesus monkeys through the use of two dominant (p11c and p199ry) and two subdominant (p68a and p56a) epitopes. using real-time pcr to quantitate t-cell receptor (tcr) variable region beta (vbeta) family usage, we show that cd ... | 2006 | 17035327 |
| simian immunodeficiency virus sivmac239 infection of major histocompatibility complex-identical cynomolgus macaques from mauritius. | nonhuman primates are widely used to study correlates of protective immunity in aids research. successful cellular immune responses have been difficult to identify because heterogeneity within macaque major histocompatibility complex (mhc) genes results in quantitative and qualitative differences in immune responses. here we use microsatellite analysis to show that simian immunodeficiency virus (siv)-susceptible cynomolgus macaques (macaca fascicularis) from the indian ocean island of mauritius ... | 2007 | 17035320 |
| chronic binge ethanol consumption accelerates progression of simian immunodeficiency virus disease. | while alcohol consumption is known to increase the incidence and severity of infections, the impact of alcohol consumption on human immunodeficiency virus (hiv) disease progression has been difficult to assess. therefore, we examined the effect of ethanol on simian immunodeficiency virus (siv) disease progression in a well-defined model utilizing rhesus macaques. | 2006 | 17010145 |
| properties of a herpes simplex virus multiple immediate-early gene-deleted recombinant as a vaccine vector. | herpes simplex virus (hsv) recombinants induce durable immune responses in rhesus macaques and mice and have induced partial protection in rhesus macaques against mucosal challenge with virulent simian immunodeficiency virus (siv). in this study, we evaluated the properties of a new generation hsv vaccine vector, an hsv-1 multiple immediate-early (ie) gene deletion mutant virus, d106, which contains deletions in the icp4, icp27, icp22, and icp47 genes. because several of the hsv ie genes have be ... | 2007 | 16996101 |
| sustained conservation of cd4+ t cells in multiprotein triple modality-immunized rhesus macaques after intrarectal challenge with simian immunodeficiency virus. | as part of a european multicenter study designed to determine the optimal combination and order of a mixed-modality vaccine against acquired immunodeficiency syndrome, rhesus monkeys received a combination of three different vectors, all expressing the same simian immunodeficiency virus (siv) genes followed by mucosal challenge with highly pathogenic siv. in the study reported here, animals were primed with dna followed by one booster immunization with semliki forest virus (sfv) and two immuniza ... | 2006 | 16987063 |
| ability of herpes simplex virus vectors to boost immune responses to dna vectors and to protect against challenge by simian immunodeficiency virus. | the immunogenicity and protective capacity of replication-defective herpes simplex virus (hsv) vector-based vaccines were examined in rhesus macaques. three macaques were inoculated with recombinant hsv vectors expressing gag, env, and a tat-rev-nef fusion protein of simian immunodeficiency virus (siv). three other macaques were primed with recombinant dna vectors expressing gag, env, and a pol-tat-nef-vif fusion protein prior to boosting with the hsv vectors. robust anti-gag and anti-env cellul ... | 2007 | 16962628 |
| distribution of simian immunodeficiency virus target cells in vaginal tissues of normal rhesus macaques: implications for virus transmission. | most new cases of hiv-1 infection occur as the result of vaginal transmission. identifying the phenotype and distribution of potential viral target cells in the vagina is important for understanding events in viral transmission and for developing effective prevention strategies. for example, compounds that prevent cd4 or ccr5 binding have been demonstrated recently to prevent vaginal transmission in rhesus macaques, but the expression and distribution of ccr5 has not been examined in the macaque ... | 2006 | 16956666 |
| virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge. | understanding the characteristics of the virus-specific t-lymphocyte response that will confer optimal protection against the clinical progression of aids will inform the development of an effective cellular immunity-based human immunodeficiency virus vaccine. we have recently shown that survival in plasmid dna-primed/recombinant adenovirus-boosted rhesus monkeys that are challenged with the simian immunodeficiency virus sivmac251 is associated with the preservation postchallenge of central memo ... | 2006 | 16943292 |
| rhesus macaque polyclonal and monoclonal antibodies inhibit simian immunodeficiency virus in the presence of human or autologous rhesus effector cells. | although antibodies can prevent or modulate lentivirus infections in nonhuman primates, the biological functions of antibody responsible for such effects are not known. we sought to determine the role of antibody-dependent cell-mediated virus inhibition (adcvi), an antibody function that inhibits virus yield from infected cells in the presence of fc receptor-bearing effector cells, in preventing or controlling sivmac251 infection in rhesus macaques (macaca mulatta). using cemx174 cells infected ... | 2006 | 16940533 |
| evidence of nk cell dysfunction in siv-infected rhesus monkeys: impairment of cytokine secretion and nkg2c/c2 expression. | defects in the adaptive immune response have been extensively characterized in human immunodeficiency virus type-1 (hiv-1)-infected individuals; however, much less is known about the function of natural killer (nk) cells during the course of hiv-1 infection. in the present study, we demonstrate that the nk cells from simian immunodeficiency virus (siv)-infected rhesus monkeys are significantly impaired in their ability to secrete ifn-gamma, tnf-alpha, and il-2, while nk cell function in siv-infe ... | 2006 | 16906533 |
| gene therapy to inhibit xenoantibody production using lentiviral vectors in non-human primates. | xenoantibodies to the gal alpha1,3 gal (gal) epitope impede the use of pig tissues for xenotransplantation, a procedure that may help overcome the shortage of human organ donors. stable gal chimerism and tolerance to gal(+) hearts could be achieved in alpha1,3-galactosyltransferase (alpha1,3gt)(-/-) mice using lentiviral vectors expressing porcine alpha1,3gt, the enzyme that synthesizes the gal carbohydrate. in this study, we evaluated whether chimerism sufficient to inhibit anti-gal xenoantibod ... | 2007 | 16886002 |
| effects of monotherapy with (r)-9-(2-phosphonylmethoxypropyl)adenine (pmpa) on the evolution of a primary simian immunodeficiency virus (siv) isolate. | determining the impact of antiretroviral therapy on virus evolution could advance the development of improved therapeutics/vaccines against hiv. toward this goal, we analyzed virus burden, quasispecies complexity, and t cell responses in siv/deltab670-infected rhesus macaques+/-treatment for 7 months with pmpa (2-30 weeks postinfection). treatment divided the animals into two groups: poor responders (a reduction of < or =1 log) and responders (> or =2 log reduction) in virus burden. virus evolut ... | 2006 | 16884757 |
| inhibition of hiv-1 replication by amphotericin b methyl ester: selection for resistant variants. | membrane cholesterol plays an important role in human immunodeficiency virus type 1 (hiv-1) particle production and infectivity. here, we have investigated the target and mechanism of action of a cholesterol-binding compound, the polyene antifungal antibiotic amphotericin b methyl ester (ame). we found that ame potently inhibited the replication of a highly divergent panel of hiv-1 isolates in various t-cell lines and primary cells irrespective of clade or target cell tropism. the defects in hiv ... | 2006 | 16882663 |
| gene expression profiling of gut mucosa and mesenteric lymph nodes in simian immunodeficiency virus-infected macaques with divergent disease course. | although the majority of drug-naïve hiv-infected patients develop acquired immunodeficiency syndrome (aids), a small percentage remains asymptomatic without therapeutic intervention. | 2006 | 16872289 |
| dynamic evolution of antibody populations in a rhesus macaque infected with attenuated simian immunodeficiency virus identified by surface plasmon resonance. | increasing evidence suggests that an effective aids vaccine will need to elicit broadly neutralizing antibody responses. however, the mechanisms of antibody-mediated neutralization have not been defined. previous studies from our lab have identified significant differences in the rates of antibody binding to trimeric siv envelope proteins that correlate with neutralization sensitivity. importantly, these results demonstrate differences in monoclonal antibody (mab) binding to neutralization-sensi ... | 2006 | 16872288 |
| systemic vaccination prevents the total destruction of mucosal cd4 t cells during acute siv challenge. | acute human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) infections are accompanied by a systemic loss of memory cd4 t cells, with mucosal sites serving as a major site for viral replication, dissemination and cd4 t cell depletion. protecting the mucosal cd4 t cell compartment thus is critical to contain hiv, and preserve the integrity of the mucosal immune system. the primary objective of this study was to determine if systemic vaccination with dna/rad-5 encoding siv-mac239- ... | 2006 | 16872285 |
| isolation of an active lv1 gene from cattle indicates that tripartite motif protein-mediated innate immunity to retroviral infection is widespread among mammals. | lv1/trim5alpha (tripartite motif 5alpha) has recently emerged as an important factor influencing species-specific permissivity to retroviral infection in a range of primates, including humans. old world monkey trim5alpha blocks human immunodeficiency virus type 1 (hiv-1) infectivity, and the human and new world monkey trim5alpha proteins are inactive against hiv-1 but active against divergent murine (n-tropic murine leukemia virus [mlv-n]) and simian (simian immunodeficiency virus from rhesus ma ... | 2006 | 16840314 |
| expression of cd8alpha identifies a distinct subset of effector memory cd4+ t lymphocytes. | circulating cd4+ cd8+ t lymphocytes have been described in the peripheral blood of humans and several animal species. however, the origin and functional properties of these cells remain poorly understood. in the present study, we evaluated the frequency, phenotype and function of peripheral cd4+ cd8+ t cells in rhesus macaques. two distinct populations of cd4+ cd8+ t cells were identified: the dominant one was cd4hi cd8lo and expressed the cd8alphaalpha homodimer, while the minor population was ... | 2006 | 16836648 |
| increased expression of interferon-inducible genes in macaque lung tissues during simian immunodeficiency virus infection. | pulmonary infections and dysfunction are frequent outcomes during the development of immunodeficiency associated with human immunodeficiency virus type 1 (hiv-1) infection, and obtaining a better understanding of the immunologic changes that occur in lungs following hiv-1 infection will provide a foundation for the development of further intervention strategies. we sought here to identify changes in the pulmonary immune environment that arise during simian immunodeficiency virus (siv) infection ... | 2006 | 16822691 |
| removal of arginine 332 allows human trim5alpha to bind human immunodeficiency virus capsids and to restrict infection. | human trim5alpha (trim5alpha(hu)) only modestly inhibits human immunodeficiency virus type 1 (hiv-1) and does not inhibit simian immunodeficiency virus (siv(mac)). alteration of arginine 332 in the trim5alpha(hu) b30.2 domain to proline, the residue found in rhesus monkey trim5alpha, has been shown to create a potent restricting factor for both hiv-1 and siv(mac.) here we demonstrate that the potentiation of hiv-1 inhibition results from the removal of a positively charged residue at position 33 ... | 2006 | 16809279 |
| simian immunodeficiency virus envelope compartmentalizes in brain regions independent of neuropathology. | simian immunodeficiency virus (siv) and human immunodeficiency virus (hiv) gp160s obtained from the brain are often genetically distinct from those isolated from other organs, suggesting the presence of brain-specific selective pressures or founder effects that result in the compartmentalization of viral quasi-species. whereas hiv has also been found to compartmentalize within different regions of the brain, the extent of brain-regional compartmentalization of siv in rhesus macaques has not been ... | 2006 | 16798669 |
| chronic alcohol consumption results in higher simian immunodeficiency virus replication in mucosally inoculated rhesus macaques. | the influence of alcohol consumption on hiv pathogenesis is not well understood. in this study we used the siv/macaque model of hiv infection to study the influence of chronic binge alcohol consumption on simian immunodeficiency virus (siv) infection. rhesus macaques were fed alcohol or isocaloric amounts of sucrose via indwelling intragastric catheters and then inoculated with sivmac251 by the rectal route. real-time rtpcr for siv gag mrna showed significantly higher plasma viral copies in alco ... | 2006 | 16796534 |
| mutational alteration of human immunodeficiency virus type 1 vif allows for functional interaction with nonhuman primate apobec3g. | human apobec3f (ha3f) and apobec3g (ha3g) are antiretroviral cytidine deaminases that can be encapsidated during virus assembly to catalyze c-->u deamination of the viral reverse transcripts in the next round of infection. lentiviruses such as human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) have evolved the accessory protein vif to induce their degradation before packaging. hiv type 1 (hiv-1) vif counteracts ha3g but not rhesus macaque apobec3g (rha3g) or african green ... | 2006 | 16731937 |
| vaccine-induced cellular immune responses reduce plasma viral concentrations after repeated low-dose challenge with pathogenic simian immunodeficiency virus sivmac239. | the goal of an aids vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory cd4 lymphocytes. here we investigated whether vaccine-induced cellular immunity in the absence of any env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic sivmac239 isolate. eight mamu-a*01-positive indian rhesus macaques were vaccinated with simian immunodeficiency virus (siv) gag, tat, rev ... | 2006 | 16731926 |
| temple monkeys and health implications of commensalism, kathmandu, nepal. | the threat of zoonotic transmission of infectious agents at monkey temples highlights the necessity of investigating the prevalence of enzootic infectious agents in these primate populations. biological samples were collected from 39 rhesus macaques at the swoyambhu temple and tested by enzyme-linked immunosorbent assay, western blot, polymerase chain reaction, or combination of these tests for evidence of infection with rhesus cytomegalovirus (rhcmv), cercopithecine herpesvirus 1 (chv-1), simia ... | 2006 | 16707044 |
| intestinal lymphocyte subsets and turnover are affected by chronic alcohol consumption: implications for siv/hiv infection. | we recently demonstrated that simian immunodeficiency virus (siv) viral loads were significantly higher in the plasma of rhesus macaques consuming alcohol compared with controls following intrarectal siv infection. to understand the possible reasons behind increased viral replication, here we assessed the effects of chronic alcohol consumption on distribution and cycling of various lymphocyte subsets in the intestine. macaques were administered alcohol (n = 11) or sucrose (n = 12), and percentag ... | 2006 | 16652027 |
| longitudinal analysis of monocyte/macrophage infection in simian immunodeficiency virus-infected, cd8+ t-cell-depleted macaques that develop lentiviral encephalitis. | the histopathological hallmark of lentiviral-associated encephalitis is an abundance of infected and activated macrophages. why a subset of infected hosts develops lentiviral encephalitis and others do not is unknown. using a cd8(+) t-cell depletion model of simian immunodeficiency virus (siv)-infected rhesus macaques, we examined the relationship between peripheral siv infection of monocytes/macrophages and the development of encephalitis. at the same time that cerebral spinal fluid viral load ... | 2006 | 16651622 |
| detection of macaque perforin expression and release by flow cytometry, immunohistochemistry, elisa, and elispot. | simian immunodeficiency virus (siv)-infection in macaques provides an important animal model for human immunodeficiency virus-1 (hiv-1) infection. the involvement of perforin (pfn), released by cytotoxic cells to mediate killing of virus-infected cells, has been difficult to assess in this experimental model due to a lack of reagents. we therefore evaluated monoclonal antibodies (mabs) pf-80, pf-164 and pf-344, previously raised against human pfn, for cross-reactivity with macaque pfn. mabs pf-1 ... | 2006 | 16647080 |
| the high-frequency major histocompatibility complex class i allele mamu-b*17 is associated with control of simian immunodeficiency virus sivmac239 replication. | particular hla alleles are associated with reduced human immunodeficiency virus replication. it has been difficult, however, to characterize the immune correlates of viral control. an analysis of the influence of major histocompatibility complex class i alleles on viral control in 181 simian immunodeficiency virus sivmac239-infected rhesus macaques revealed that mamu-b(*)17 was associated with a 26-fold reduction in plasma virus concentrations (p<0.001). mamu-b(*)17 was also enriched in a group ... | 2006 | 16641299 |
| host response and dysfunction in the cns during chronic simian immunodeficiency virus infection. | cns abnormalities can be detected during chronic human immunodeficiency virus (hiv) infection, before the development of opportunistic infections or other sequelae of immunodeficiency. however, although end-stage dementia caused by hiv has been linked to the presence of infected and activated macrophages and microglia in the brain, the nature of the changes resulting in the motor and cognitive disorders in the chronic stage is unknown. using simian immunodeficiency virus-infected rhesus monkeys, ... | 2006 | 16641237 |
| hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity. | a common viral immune evasion strategy involves mutating viral surface proteins in order to evade host neutralizing antibodies. such immune evasion tactics have not previously been intentionally applied to the development of novel viral gene delivery vectors that overcome the critical problem of anti-vector immunity. recombinant, replication-incompetent adenovirus serotype 5 (rad5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens have proved highly immunogenic in ... | 2006 | 16625206 |
| independence of granzyme b secretion and interferon- gamma production during acute simian immunodeficiency virus infection. | quantification of interferon (ifn)-gamma by enzyme-linked immunospot (elispot) assay is currently used as a surrogate measurement of cytotoxic t lymphocyte (ctl) activity in nonhuman primates, particularly in simian immunodeficiency virus (siv) models. given that noncytotoxic cells and natural killer cells can also release ifn-gamma, quantification of granzyme b (grb), a molecule secreted predominantly by activated cd8+ t cells, may represent an additional surrogate measurement of ctl activity. | 2006 | 16619193 |
| immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the g protein of vesicular stomatitis virus. | vaccination with exogenous antigens such as recombinant viral proteins, immunodeficiency virus-derived whole inactivated virus particles, or virus-like particles (vlp) has generally failed to provide sufficient protection in animal models for aids. pseudotyping vlps with the vesicular stomatitis virus g protein (vsv-g), which is known to mediate entry into dendritic cells, might allow more efficient stimulation of immune responses. therefore, we pseudotyped noninfectious immunodeficiency virus-l ... | 2006 | 16616946 |
| importance of the n-distal ap-2 binding element in nef for simian immunodeficiency virus replication and pathogenicity in rhesus macaques. | point mutations in sivmac239 nef disrupting cd4 downmodulation and enhancement of virion infectivity attenuate viral replication in acutely infected rhesus macaques, but changes selected later in infection fully restore nef function (a. j. iafrate et al., j. virol. 74:9836-9844, 2000). to further evaluate the relevance of these nef functions for viral persistence and disease progression, we analyzed an sivmac239 nef mutant containing a deletion of amino acids q64 to n67 (delta64-67nef). this mut ... | 2006 | 16611907 |
| enhanced replication of simian immunodeficiency virus adjacent to catecholaminergic varicosities in primate lymph nodes. | clinical and in vitro studies have shown that activity of the autonomic nervous system (ans) can stimulate lentivirus replication. to define the potential anatomical basis for this effect, we analyzed the spatial relationship between catecholaminergic neural fibers and sites of simian immunodeficiency virus (siv) replication in lymph nodes from rhesus macaques experimentally infected with sivmac251. viral replication was mapped by in situ hybridization for siv env, gag, and nef rna, and catechol ... | 2006 | 16611891 |
| rapid dissemination of a pathogenic simian/human immunodeficiency virus to systemic organs and active replication in lymphoid tissues following intrarectal infection. | a better understanding of virological events during the early phase of human immunodeficiency virus 1 (hiv-1) infection is important for development of effective antiviral vaccines. in this study, by using quantitative pcr and an infectious plaque assay, virus distribution and replication were examined in various internal organs of rhesus macaques for almost 1 month after intrarectal inoculation of a pathogenic simian immunodeficiency virus/hiv chimeric virus (shiv-c2/1-ks661c). at 3 days post-i ... | 2006 | 16603534 |
| genetic analysis of simian immunodeficiency virus expressed in milk and selectively transmitted through breastfeeding. | to develop effective intervention strategies that prevent breast milk transmission of human immunodeficiency virus (hiv), we must understand the specific viral properties and mechanisms responsible for infant infection. we have used lactating rhesus macaques infected with a pathogenic simian immunodeficiency virus (siv) stock to analyze the viral genotypes expressed in plasma and milk throughout the disease course and to identify those variants ultimately transmitted to infants through breastfee ... | 2006 | 16571789 |
| systemic arteriopathy in siv-infected rhesus macaques (macaca mulatta). | background: severe disseminated vasculopathy was observed in two simian immunodeficiency virus (siv)-infected rhesus macaques (macaca mulatta). these animals developed clinical signs of aids, including lymphadenopathy, weight loss, diarrhea and collapse. results and discussion: grossly, both animals showed emaciation, lymphadenopathy, vegetations on the mitral valve, renal infarcts and a dilated intestine; one animal had multifocal hemorrhages in multiple organs. histologically, both cases had d ... | 2006 | 16556297 |
| effects of busulfan dose escalation on engraftment of infant rhesus monkey hematopoietic stem cells after gene marking by a lentiviral vector. | non-myeloablative cytoreduction is used in clinical hematopoietic stem cell gene therapy trials to increase engraftment of gene-modified cells. we utilized an infant rhesus monkey model to identify an optimal dosage of busulfan that results in efficient long-term gene marking with minimal toxicities. | 2006 | 16543071 |
| construction of gag-chimeric viruses between hiv-1 and sivmac that are capable of productive multi-cycle infection. | forty-nine recombinant viral clones between human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus from the rhesus monkey (sivmac), which carry chimeric gag (capsid/p2 region) genes in the background of the hiv-1 genome, were constructed to establish an hiv-1/monkey infection model system for human aids. upon transfection, all the recombinants generated progeny virions at a level comparable to the parental hiv-1 clone and no major abnormalities were found in the virions, a ... | 2006 | 16520079 |
| the hiv-1 clade c promoter is particularly well adapted to replication in the gut in primary infection. | coinfection of rhesus macaques with human/simian immunodeficiency virus chimeras harbouring the minimal core-promoter/enhancer elements from hiv-1 clade b, c and e viral prototypes (str-b, str-c and str-e) revealed a remarkable dichotomy in terms of spatio-temporal viral replication. the clade c chimera (str-c) predominated in primary infection. the present study was aimed at identifying the origin of str-c plasma viraemia at this infection phase. | 2006 | 16514295 |
| x-ray crystallographic characterization of rhesus macaque mhc mamu-a*02 complexed with an immunodominant siv-gag nonapeptide. | simian immunodeficiency virus (siv) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in hiv vaccine strategies and therapeutics by characterizing various cytotoxic t-lymphocyte (ctl) responses in macaque monkeys. however, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class i (mhc i) molecules remains extremely limited. here, a complex of the rhesus macaque mhc i molecule (mamu-a*02) with human ... | 2006 | 16511250 |
| complex assembly, crystallization and preliminary x-ray crystallographic studies of rhesus macaque mhc mamu-a*01 complexed with an immunodominant siv-gag nonapeptide. | simian immunodeficiency virus (siv) infection in rhesus macaques has been used as the best model for the study of human immunodeficiency virus (hiv) infection in humans, especially in the cytotoxic t-lymphocyte (ctl) response. however, the structure of rhesus macaque (or any other monkey model) major histocompatibility complex class i (mhc i) presenting a specific peptide (the ligand for ctl) has not yet been elucidated. here, using in vitro refolding, the preparation of the complex of the rhesu ... | 2005 | 16511111 |
| intestinal double-positive cd4+cd8+ t cells are highly activated memory cells with an increased capacity to produce cytokines. | peripheral blood and intestinal cd4+cd8+ double-positive (dp) t cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. here we demonstrate that dp t cells are abundant in the intestinal lamina propria of normal rhesus macaques (macaca mulatta). moreover, dp t cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen s ... | 2006 | 16506292 |
| perforin expression in the gastrointestinal mucosa is limited to acute simian immunodeficiency virus infection. | perforin-mediated cytotoxicity is a major effector function of virus-specific cd8 t cells. we have investigated the expression of perforin in the gut, an important site of simian immunodeficiency virus (siv) pathogenesis, during experimental siv infection of rhesus macaques. we observed significant increases in perforin protein and mrna expression levels in the colons of siv-infected macaques as early as 21 days after infection. however, during chronic infection, despite ongoing viral replicatio ... | 2006 | 16501118 |
| th-1-type cytotoxic cd8+ t-lymphocyte responses to simian immunodeficiency virus (siv) are a consistent feature of natural siv infection in sooty mangabeys. | sooty mangabeys are a natural host of simian immunodeficiency virus (siv) that remain asymptomatic and do not exhibit increased immune activation or increased t-lymphocyte turnover despite sustained high levels of siv viremia. in this study we asked whether an altered immune response to siv contributes to the lack of immunopathology in sooty mangabeys as opposed to species with pathogenic lentivirus infection. siv-specific cellular immune responses were investigated in a cohort of 25 sooty manga ... | 2006 | 16501086 |