Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| infectivity and neutralization of simian immunodeficiency virus with flag epitope insertion in gp120 variable loops. | a flag epitope tag was substituted within variable loop 1 (v1), 2 (v2), or 4 (v4) of the gp120 envelope glycoprotein of simian immunodeficiency virus strain 239 (siv239) to evaluate the extent to which each variable loop may serve as a target for antibody-mediated neutralization. two sites within each variable loop of siv239 were chosen for individual epitope tag insertions. flag epitope substitutions were also made in the v1, v2, and v4 loops of a neutralization-sensitive derivative of siv239, ... | 2007 | 17686865 |
| social stress enhances sympathetic innervation of primate lymph nodes: mechanisms and implications for viral pathogenesis. | behavioral processes regulate immune system function in part via direct sympathetic innervation of lymphoid organs, but little is known about the factors that regulate the architecture of neural fibers in lymphoid tissues. in the present study, we find that experimentally imposed social stress can enhance the density of catecholaminergic neural fibers within axillary lymph nodes from adult rhesus macaques. this effect is linked to increased transcription of the key sympathetic neurotrophin nerve ... | 2007 | 17699667 |
| severe depletion of mucosal cd4+ t cells in aids-free simian immunodeficiency virus-infected sooty mangabeys. | hiv-infected humans and siv-infected rhesus macaques experience a rapid and dramatic loss of mucosal cd4+ t cells that is considered to be a key determinant of aids pathogenesis. in this study, we show that nonpathogenic siv infection of sooty mangabeys (sms), a natural host species for siv, is also associated with an early, severe, and persistent depletion of memory cd4+ t cells from the intestinal and respiratory mucosa. importantly, the kinetics of the loss of mucosal cd4+ t cells in sms is s ... | 2007 | 17709517 |
| acute loss of intestinal cd4+ t cells is not predictive of simian immunodeficiency virus virulence. | the predictive value of acute gut-associated lymphoid tissue (galt) cd4+ t cell depletion in lentiviral infections was assessed by comparing three animal models illustrative of the outcomes of siv infection: pathogenic infection (sivsmm infection of rhesus macaques (rh)), persistent nonprogressive infection (sivagm infection of african green monkeys (agm)), and transient, controlled infection (sivagm infection of rh). massive acute depletion of galt cd4+ t cells was a common feature of acute siv ... | 2007 | 17709518 |
| neuroinvasion of fluorescein-positive monocytes in acute simian immunodeficiency virus infection. | monocytes and macrophages play a central role in the pathogenesis of human immunodeficiency virus (hiv)-associated dementia. they represent prominent targets for hiv infection and are thought to facilitate viral neuroinvasion and neuroinflammatory processes. however, many aspects regarding monocyte brain recruitment in hiv infection remain undefined. the nonhuman primate model of aids is uniquely suited for examination of the role of monocytes in the pathogenesis of aids-associated encephalitis. ... | 2007 | 17715237 |
| clinical measles after measles virus challenge in simian immunodeficiency virus-infected measles virus-vaccinated rhesus monkeys. | understanding the impact of human immunodeficiency virus (hiv) infection on the clinical manifestations and kinetics of measles virus (mv) replication in mv-vaccinated and unvaccinated individuals is important for developing successful vaccine strategies for measles eradication. to model the pathogenesis of mv infection in mv-vaccinated and unvaccinated individuals infected with hiv, previously vaccinated and unvaccinated rhesus monkeys infected with simian immunodeficiency virus (siv) were chal ... | 2007 | 18190259 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| immune-response profiles induced by human immunodeficiency virus type 1 vaccine dna, protein or mixed-modality immunization: increased protection from pathogenic simian-human immunodeficiency virus viraemia with protein/dna combination. | current data suggest that prophylactic human immunodeficiency virus type 1 (hiv) vaccines will be most efficacious if they elicit a combination of adaptive humoral and t-cell responses. here, we explored the use of different vaccine strategies in heterologous prime-boost regimes and evaluated the breadth and nature of immune responses in rhesus monkeys induced by epidermally delivered plasmid dna or recombinant hiv proteins formulated in the as02a adjuvant system. these immunogens were administe ... | 2008 | 18198386 |
| impact of glycosylation on antigenicity of simian immunodeficiency virus siv239: induction of rapid v1/v2-specific non-neutralizing antibody and delayed neutralizing antibody following infection with an attenuated deglycosylated mutant. | infection of rhesus macaques with a deglycosylation mutant, delta5g, derived from siv239, a pathogenic clone of simian immunodeficiency virus (siv), led to robust acute-phase viral replication followed by a chronic phase with undetectable viral load. this study examined whether humoral responses in delta5g-infected animals played any role in the control of infection. neutralizing antibodies (nabs) were elicited more efficiently in delta5g-infected animals than in siv239-infected animals. however ... | 2008 | 18198387 |
| selective downregulation of rhesus macaque and sooty mangabey major histocompatibility complex class i molecules by nef alleles of simian immunodeficiency virus and human immunodeficiency virus type 2. | human immunodeficiency virus type 1 (hiv-1) nef downregulates hla-a and -b molecules, but not hla-c or -e molecules, based on amino acid differences in their cytoplasmic domains to simultaneously evade cytotoxic t lymphocyte (ctl) and natural killer cell surveillance. rhesus macaques and sooty mangabeys express orthologues of hla-a, -b, and -e, but not hla-c, and many of these molecules have unique amino acid differences in their cytoplasmic tails. we found that these differences also resulted i ... | 2008 | 18199657 |
| use of an anti-cd16 antibody for in vivo depletion of natural killer cells in rhesus macaques. | non-human primates serve as key animal models for a variety of viral infections. to evaluate the contribution of natural killer (nk) cells to the immune-mediated control of these viruses in macaque monkeys, we have described a method for depleting nk cells in vivo by administration of anti-human cd16 mouse monoclonal antibody. using a fluorometric nk-cell cytotoxicity assay, we show that most nk-cell cytotoxicity in rhesus monkey peripheral blood mononuclear cells resides in the cd16(+) and/or c ... | 2008 | 18201184 |
| effect of morphine on the neuropathogenesis of sivmac infection in indian rhesus macaques. | morphine is known to prevent the development of cell-mediated immune (cmi) responses and enhance expression of the ccr5 receptor in monocyte macrophages. we undertook a study to determine the effect of morphine on the neuropathogenesis and immunopathogenesis of simian immunodeficiency virus (siv) infection in indian rhesus macaques. hypothetically, the effect of morphine would be to prevent the development of cmi responses to siv and to enhance the infection in macrophages. sixteen rhesus macaqu ... | 2008 | 18247128 |
| vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral dna vaccine. | studies in non-human primates, with simian immunodeficiency virus (siv) and simian/human immunodeficiency virus (shiv) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. this report describes a vif- ... | 2008 | 18261756 |
| soluble pd-1 rescues the proliferative response of simian immunodeficiency virus-specific cd4 and cd8 t cells during chronic infection. | phenotypic and functional studies of the programmed death-1 (pd-1) molecule on cd4(+) and cd8(+) t cells were performed on peripheral blood mononuclear cells from uninfected and simian immunodeficiency virus (siv)-infected rhesus macaques. these data demonstrated a rapid upregulation of pd-1 expression on tetramer-positive cd8(+) t cells from mamua.01(+) siv-infected macaques upon infection. upregulation of pd-1 on total cd8(+) t cells was not detectable. in contrast, cd4(+) t-cell pd-1 expressi ... | 2008 | 18266718 |
| dermatitis in a rhesus macaque (macaca mulatta) experimentally infected with simian immunodeficiency virus. | dermatopathies are common with human immunodeficiency virus (hiv) infection, affecting an estimated 90% of hiv patients. opportunistic infections are common and include viral, bacterial and fungal etiologies. dermal eruptions from highly active anti-retroviral therapy (haart) or antibiotics such as trimethoprim-sulfamethoxazole (tms) are also common, and can be challenging to differentiate from other causes of dermatitis. presented is a challenging dermatology case involving a six year old male ... | 2008 | 18269525 |
| genital ulcers facilitate rapid viral entry and dissemination following intravaginal inoculation with cell-associated simian immunodeficiency virus sivmac239. | here we report the results of studies in the simian immunodeficiency virus (siv)-rhesus macaque model of intravaginal transmission of human immunodeficiency virus type 1 in the setting of genital ulcerative diseases. we document preferential association of vrna with induced ulcers during the first days of infection and show that allogeneic cells of the inoculum traffic from the vaginal lumen to lymphatic tissues. this surprisingly rapid systemic dissemination in this cell-associated siv challeng ... | 2008 | 18272571 |
| vaccine protection by live, attenuated simian immunodeficiency virus in the absence of high-titer antibody responses and high-frequency cellular immune responses measurable in the periphery. | an attenuated derivative of simian immunodeficiency virus strain 239 deleted of v1-v2 sequences in the envelope gene (siv239deltav1-v2) was used for vaccine/challenge experiments in rhesus monkeys. peak levels of viral rna in plasma of 10(4) to 10(6.5) copies/ml in the weeks immediately following inoculation of siv239deltav1-v2 were 10- to 1,000-fold lower than those observed with parental siv239 ( approximately 10(7.3) copies/ml). viral loads consistently remained below 200 copies/ml after 8 we ... | 2008 | 18272584 |
| viral and host correlates of serum resistin in simian aids. | resistin is an adipocytokine with a proposed dual role in metabolism and inflammation. in light of the ability to promote inflammatory responses, adipocytokines may prove key factors in modulating the host response to hiv. this study utilizes the simian immunodeficiency virus (siv) model of hiv/aids to investigate changes in serum resistin levels following dietary intervention and siv infection and determine associations with measures of body composition and disease severity. resistin levels, bo ... | 2008 | 18275346 |
| metabolic markers of neuronal injury correlate with siv cns disease severity and inoculum in the macaque model of neuroaids. | in vivo mr spectroscopy (mrs) studies have shown reductions in naa/cr levels in patients with severe neurocognitive deficits due to aids dementia complex (adc), also known as neuroaids. the relationship between the cellular changes within the brain during neuroaids and the role of naa/cr as a metabolic marker remains unclear. in order to clarify the relationship between naa/cr and disease severity we utilized the simian immunodeficiency virus (siv)/macaque model of encephalitis. high-field proto ... | 2008 | 18306400 |
| abrogation of aids vaccine-induced cytotoxic t-lymphocyte efficacy in vivo due to a change in viral epitope flanking sequences. | a current promising aids vaccine strategy is to elicit cd8(+) cytotoxic t lymphocyte (ctl) responses that broadly recognize highly-diversified hivs. in our previous vaccine trial eliciting simian immunodeficiency virus (siv) mac239 gag-specific ctl responses, a group of burmese rhesus macaques possessing a major histocompatibility complex haplotype 90-120-ia have shown vaccine-based viral control against a homologous sivmac239 challenge. vaccine-induced gag(206-216) epitope-specific ctl response ... | 2008 | 18316225 |
| antigenic stimulation in the simian model of hiv infection yields dilated cardiomyopathy through effects of tnfalpha. | to investigate a role for endogenous myocardial cytokine production in the development of hiv-associated cardiomyopathy. | 2008 | 18316999 |
| transmission of simian immunodeficiency virus carrying multiple cytotoxic t-lymphocyte escape mutations with diminished replicative ability can result in aids progression in rhesus macaques. | cytotoxic t-lymphocyte (ctl) responses frequently select for immunodeficiency virus mutations that result in escape from ctl recognition with viral fitness costs. the replication in vivo of such viruses carrying not single but multiple escape mutations in the absence of the ctl pressure has remained undetermined. here, we have examined the replication of simian immunodeficiency virus (siv) with five gag mutations selected in a macaque possessing the major histocompatibility complex haplotype 90- ... | 2008 | 18337572 |
| contribution of cd8+ t cells to containment of viral replication and emergence of mutations in mamu-a*01-restricted epitopes in simian immunodeficiency virus-infected rhesus monkeys. | here, we investigated the containment of virus replication in simian immunodeficiency virus (siv) infection by cd8(+) lymphocytes. escape mutations in mamu-a*01 epitopes appeared first in siv tat tl8 and then in siv gag p11c. the appearance of escape mutations in siv gag p11c was coincident with compensatory changes outside of the epitope. eliminating cd8(+) lymphocytes from rhesus monkeys during primary infection resulted in more rapid disease progression that was associated with preservation o ... | 2008 | 18367519 |
| increased loss of ccr5+ cd45ra- cd4+ t cells in cd8+ lymphocyte-depleted simian immunodeficiency virus-infected rhesus monkeys. | previously we have shown that cd8(+) t cells are critical for containment of simian immunodeficiency virus (siv) viremia and that rapid and profound depletion of cd4(+) t cells occurs in the intestinal tract of acutely infected macaques. to determine the impact of siv-specific cd8(+) t-cell responses on the magnitude of the cd4(+) t-cell depletion, we investigated the effect of cd8(+) lymphocyte depletion during primary siv infection on cd4(+) t-cell subsets and function in peripheral blood, lym ... | 2008 | 18367534 |
| simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes salmonella dissemination from the gut. | salmonella typhimurium causes a localized enteric infection in immunocompetent individuals, whereas hiv-infected individuals develop a life-threatening bacteremia. here we show that simian immunodeficiency virus (siv) infection results in depletion of t helper type 17 (th17) cells in the ileal mucosa of rhesus macaques, thereby impairing mucosal barrier functions to s. typhimurium dissemination. in siv-negative macaques, the gene expression profile induced by s. typhimurium in ligated ileal loop ... | 2008 | 18376406 |
| comprehensive immunological evaluation reveals surprisingly few differences between elite controller and progressor mamu-b*17-positive simian immunodeficiency virus-infected rhesus macaques. | the association between particular major histocompatibility complex class i (mhc-i) alleles and control of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) replication implies that certain cd8(+) t-lymphocyte (cd8-tl) responses are better able than others to control viral replication in vivo. however, possession of favorable alleles does not guarantee improved prognosis or viral control. in rhesus macaques, the mhc-i allele mamu-b*17 is correlated with reduced viremia a ... | 2008 | 18385251 |
| tissue-specific restriction of cyclophilin a-independent hiv-1- and siv-derived lentiviral vectors. | the host factor alpha isoform of the tripartite motif 5 (trim5alpha) restricts human immunodeficiency virus type 1 (hiv-1) infection in certain non-human primate species. restriction of hiv-1 is enhanced by binding of the viral capsid to cyclophilin a (cypa) in target cells, although cypa is not absolutely required for restriction in rhesus macaque cells. simian immunodeficiency virus (siv) is not restricted by rhesus macaque trim5alpha and its capsid does not bind to cypa. here, the effect of l ... | 2008 | 18385767 |
| in vivo natural killer cell depletion during primary simian immunodeficiency virus infection in rhesus monkeys. | the contribution of natural killer (nk) cells to the immune containment of human immunodeficiency virus infection remains undefined. to directly assess the role of nk cells in an aids animal model, we depleted rhesus monkeys of >88% of cd3(-) cd16(+) cd159a(+) nk cells at the time of primary simian immunodeficiency virus (siv) infection by using anti-cd16 antibody. during the first 11 days following siv inoculation, when nk cell depletion was most profound, a trend toward higher levels of siv re ... | 2008 | 18434394 |
| incomplete protection against simian immunodeficiency virus vaginal transmission in rhesus macaques by a topical antiviral agent revealed by repeat challenges. | the rising prevalence of human immunodeficiency virus type 1 (hiv-1) infection in women, especially in resource-limited settings, accentuates the need for accessible, inexpensive, and female-controlled preexposure prophylaxis strategies to prevent mucosal transmission of the virus. while many compounds can inactivate hiv-1 in vitro, evaluation in animal models for mucosal transmission of virus may help identify which approaches will be effective in vivo. macaques challenged intravaginally with p ... | 2008 | 18434406 |
| efficient entry inhibition of human and nonhuman primate immunodeficiency virus by cell surface-expressed gp41-derived peptides. | membrane-anchored c-peptides (for example, mac46) derived from human immunodeficiency virus type 1 (hiv-1) envelope glycoprotein gp41 effectively inhibit hiv-1 entry in cell lines and primary human cd4+ cells in vitro. here we evaluated this gene therapy approach in animal models of aids. we adapted the hiv gp41-derived mac46 vector construct for use in rhesus monkeys. simian immunodeficiency virus (siv and shiv) sequence-adapted mac46 peptides, and the original hiv-1-derived mac46 expressed on ... | 2008 | 18449216 |
| increased expression of monocyte cd44v6 correlates with the deveopment of encephalitis in rhesus macaques infected with simian immunodeficiency virus. | in people infected with human immunodeficiency virus type 1 (hiv-1), the accumulation of macrophages in the brain correlates with encephalitis and dementia. we hypothesized that a pattern of surface marker expression in blood monocytes may serve as a marker for central nervous system (cns) disease. using the simian immunodeficiency virus (siv)-rhesus monkey model, we analyzed functionally relevant surface markers on monocytes and macrophages from the blood and brain in animals that did or did no ... | 2008 | 18471064 |
| the role of the armadillo and sooty mangabey monkey in human leprosy. | the armadillo was the first animal model of leprosy. its role in the transmission of leprosy remains controversial. the sooty mangabey model of leprosy led to the discovery that rhesus monkeys were more susceptible to leprosy when coinfected with simian immunodeficiency virus (siv), but that leprosy may play a protective role against acquired immunodeficiency syndrome (aids) mortality. recently, molecular methods have been developed for leprosy and may help resolve the role of zoonoses in lepros ... | 2008 | 18477141 |
| mhc class i characterization of indonesian cynomolgus macaques. | cynomolgus macaques (macaca fascicularis) are quickly becoming a useful model for infectious disease and transplantation research. even though cynomolgus macaques from different geographic regions are used for these studies, there has been limited characterization of full-length major histocompatibility complex (mhc) class i immunogenetics of distinct geographic populations. here, we identified 48 mhc class i cdna nucleotide sequences in eleven indonesian cynomolgus macaques, including 41 novel ... | 2008 | 18504574 |
| [comparison of intravenous and intrarectal sivmac239 infections in rhesus monkeys of chinese origin]. | to investigate the biological and clinical features of chinese rhesus monkeys after intravenous (iv) and intrarectal (ir) challenge with sivmac239 in rhesus monkeys of chinese origin, and compare the differences between the routes of infection. | 2008 | 18505116 |
| ccaat/enhancer binding protein beta is a major mediator of inflammation and viral replication in the gastrointestinal tract of simian immunodeficiency virus-infected rhesus macaques. | the gastrointestinal tract (git) is a major target of infection with human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv). chronic git disease and inflammation are common sequelae to hiv/siv infection. nonetheless, the molecular mechanisms that cause and maintain git dysfunction remain unclear. we investigated the contribution of ccaat/enhancer-binding protein beta (c/ebpbeta) to git disease and viral replication in jejunum and colon collected at necropsy from 12 siv-infect ... | 2008 | 18535173 |
| nonhuman primate models and the failure of the merck hiv-1 vaccine in humans. | the adenovirus type 5 (ad5)-based vaccine developed by merck failed to either prevent hiv-1 infection or suppress viral load in subsequently infected subjects in the step human phase 2b efficacy trial. analogous vaccines had previously also failed in the simian immunodeficiency virus (siv) challenge-rhesus macaque model. in contrast, vaccine protection studies that used challenge with a chimeric simian-human immunodeficiency virus (shiv89.6p) in macaques did not predict the human trial results. ... | 2008 | 18535579 |
| chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virological effects. | the reverse transcriptase (rt) inhibitor tenofovir (tfv) is highly effective in the simian immunodeficiency virus (siv) macaque model of human immunodeficiency virus infection. the current report describes extended safety and efficacy data on 32 animals that received prolonged (>or=1- to 13-year) daily subcutaneous tfv regimens. the likelihood of renal toxicity (proximal renal tubular dysfunction [prtd]) correlated with plasma drug concentrations, which depended on the dosage regimen and age-rel ... | 2008 | 18573931 |
| capsid proteins from human immunodeficiency virus type 1 and simian immunodeficiency virus sivmac can coassemble into mature cores of infectious viruses. | we have recently shown that the gag polyproteins from human immunodeficiency virus type 1 (hiv-1) and hiv-2 can coassemble and functionally complement each other. during virion maturation, the gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (ca), which refolds and forms the outer shell of a cone-shaped mature core. less than one-half of the ca proteins present within the hiv-1 virion are required to form the mature core. therefore, it is unclear whether ... | 2008 | 18579598 |
| cd4 deficits and disease course acceleration can be driven by a collapse of the cd8 response in rhesus macaques infected with simian immunodeficiency virus. | defects in memory cd4+ t cells correlate with development of aids in monkeys infected with simian immunodeficiency virus, but the early events leading to these deficits are unknown. we explored the role of cells specific to simian immunodeficiency virus and cd8 cells in the determination of cd4 failure and rapid disease course. | 2008 | 18614867 |
| potent antibody-mediated neutralization and evolution of antigenic escape variants of simian immunodeficiency virus strain sivmac239 in vivo. | here, we describe the evolution of antigenic escape variants in a rhesus macaque that developed unusually high neutralizing antibody titers to sivmac239. by 42 weeks postinfection, 50% neutralization of sivmac239 was achieved with plasma dilutions of 1:1,000. testing of purified immunoglobulin confirmed that the neutralizing activity was antibody mediated. despite the potency of the neutralizing antibody response, the animal displayed a typical viral load profile and progressed to terminal aids ... | 2008 | 18667507 |
| reduced protection from simian immunodeficiency virus sivmac251 infection afforded by memory cd8+ t cells induced by vaccination during cd4+ t-cell deficiency. | adaptive cd4(+) and cd8(+) t-cell responses have been associated with control of human immunodeficiency virus/simian immunodeficiency virus (hiv/siv) replication. here, we have designed a study with indian rhesus macaques to more directly assess the role of cd8 siv-specific responses in control of viral replication. macaques were immunized with a dna prime-modified vaccinia virus ankara (mva)-siv boost regimen under normal conditions or under conditions of antibody-induced cd4(+) t-cell deficien ... | 2008 | 18667509 |
| gag-specific cytotoxic t-lymphocyte-based control of primary simian immunodeficiency virus replication in a vaccine trial. | gag-specific cytotoxic t lymphocytes (ctls) exert strong suppressive pressure on human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) replication. however, it has remained unclear whether they can actually contain primary viral replication. recent trials of prophylactic vaccines inducing virus-specific t-cell responses have indicated their potential to confer resistance against primary siv replication in rhesus macaques, while the immunological determinant for this vaccine- ... | 2008 | 18667518 |
| prevention of siv rectal transmission and priming of t cell responses in macaques after local pre-exposure application of tenofovir gel. | the rectum is particularly vulnerable to hiv transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. in the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (arv) drugs. to prevent mucosal transmission of hiv, a microbicide ... | 2008 | 18684007 |
| the role of production frequency in the sharing of simian immunodeficiency virus-specific cd8+ tcrs between macaques. | in some epitope-specific responses, t cells bearing identical tcrs occur in many mhc-matched individuals. the sharing of public tcrs is unexpected, given the enormous potential diversity of the tcr repertoire. we have previously studied the sharing of tcr beta-chains in the cd8(+) t cell responses to two influenza epitopes in mice. analysis of these tcrbeta repertoires suggests that, even with unbiased v(d)j recombination mechanisms, some tcrbetas can be produced more frequently than others, by ... | 2008 | 18684950 |
| potent simian immunodeficiency virus-specific cellular immune responses in the breast milk of simian immunodeficiency virus-infected, lactating rhesus monkeys. | breast milk transmission of hiv is a leading cause of infant hiv/aids in the developing world. remarkably, only a small minority of breastfeeding infants born to hiv-infected mothers contract hiv via breast milk exposure, raising the possibility that immune factors in the breast milk confer protection to the infants who remain uninfected. to model hiv-specific immunity in breast milk, lactation was pharmacologically induced in mamu-a*01(+) female rhesus monkeys. the composition of lymphocyte sub ... | 2008 | 18714039 |
| sequential priming with simian immunodeficiency virus (siv) dna vaccines, with or without encoded cytokines, and a replicating adenovirus-siv recombinant followed by protein boosting does not control a pathogenic sivmac251 mucosal challenge. | previously, combination dna/nonreplicating adenovirus (ad)- or poxvirus-vectored vaccines have strongly protected against shiv(89.6p), dnas expressing cytokines have modulated immunity elicited by dna vaccines, and replication-competent ad-recombinant priming and protein boosting has strongly protected against simian immunodeficiency virus (siv) challenge. here we evaluated a vaccine strategy composed of these promising components. seven rhesus macaques per group were primed twice with multigeni ... | 2008 | 18753198 |
| rhesus macaque rhadinovirus-associated non-hodgkin lymphoma: animal model for kshv-associated malignancies. | rhesus macaque rhadinovirus (rrv) is closely related to kaposi sarcoma-associated herpesvirus (kshv) and is associated with the development of b-cell hyperplasia and persistent lymphadenopathy resembling multicentric castleman disease in rhesus macaques (rms) coinfected with simian immunodeficiency virus (siv). here we investigated whether rms experimentally infected with siv and rrv can develop other disease manifestations observed in hiv- and kshv-infected patients. as reported earlier, inocul ... | 2008 | 18757778 |
| adenoviral hepatitis in a siv-infected rhesus monkey (macaca mulatta). | a 5-year-old female rhesus monkey infected with simian immunodeficiency virus became clinically suspicious with anorexia, increasing weakness and apathy eighty-five weeks after the tonsillar virus inoculation and was euthanised due to a poor prognosis. | 2008 | 18773508 |
| monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: lessons from human and nonhuman primate studies. | here the authors discuss evidence in human and animal models supporting two opposing views regarding the pathogenesis of human immunodeficiency virus (hiv) in the central nervous system (cns): (1) hiv infection in the cns is a compartmentalized infection, with the virus-infected macrophages entering the cns early, infecting resident microglia and astrocytes, and achieving a state of latency with evolution toward a fulminant cns infection late in the course of disease; or alternatively, (2) event ... | 2008 | 18780233 |
| with minimal systemic t-cell expansion, cd8+ t cells mediate protection of rhesus macaques immunized with attenuated simian-human immunodeficiency virus shiv89.6 from vaginal challenge with simian immunodeficiency virus. | the presence, at the time of challenge, of antiviral effector t cells in the vaginal mucosa of female rhesus macaques immunized with live-attenuated simian-human immunodeficiency virus 89.6 (shiv89.6) is associated with consistent and reproducible protection from pathogenic simian immunodeficiency virus (siv) vaginal challenge (18). here, we definitively demonstrate the protective role of the siv-specific cd8(+) t-cell response in shiv-immunized monkeys by cd8(+) lymphocyte depletion, an interve ... | 2008 | 18787003 |
| divergent tlr7 and tlr9 signaling and type i interferon production distinguish pathogenic and nonpathogenic aids virus infections. | pathogenic hiv infections of humans and simian immunodeficiency virus (siv) infections of rhesus macaques are characterized by generalized immune activation and progressive cd4(+) t cell depletion. in contrast, natural reservoir hosts for siv, such as sooty mangabeys, do not progress to aids and show a lack of aberrant immune activation and preserved cd4(+) t cell populations, despite high levels of siv replication. here we show that sooty mangabeys have substantially reduced levels of innate im ... | 2008 | 18806803 |
| intestinal double-positive cd4+cd8+ t cells of neonatal rhesus macaques are proliferating, activated memory cells and primary targets for sivmac251 infection. | peripheral blood and thymic double-positive (dp) cd4(+)cd8(+) t cells from neonates have been described earlier, but the function and immunophenotypic characteristics of other tissue-derived dp t cells are not clearly understood. here, we demonstrate the functional and immunophenotypic characteristics of dp cells in 6 different tissues, including thymus from normal neonatal rhesus macaques (macaca mulatta) between 0 and 21 days of age. in general, intestinal dp t cells of neonates have higher pe ... | 2008 | 18820133 |
| simian immunodeficiency virus (siv)-specific cd8+ t-cell responses in vervet african green monkeys chronically infected with sivagm. | african green monkeys (agm) do not develop overt signs of disease following simian immunodeficiency virus (siv) infection. while it is still unknown how natural hosts like agm can cope with this lentivirus infection, a large number of investigations have shown that cd8(+) t-cell responses are critical for the containment of aids viruses in humans and asian nonhuman primates. here we have compared the phenotypes of t-cell subsets and magnitudes of siv-specific cd8(+) t-cell responses in vervet ag ... | 2008 | 18829748 |
| glycosylation of gp41 of simian immunodeficiency virus shields epitopes that can be targets for neutralizing antibodies. | human immunodeficiency virus type 1 and simian immunodeficiency virus possess three closely spaced, highly conserved sites for n-linked carbohydrate attachment in the extracellular domain of the transmembrane protein gp41. we infected rhesus monkeys with a variant of cloned sivmac239 lacking the second and third sites or with a variant strain lacking all three of sivmac239's glycosylation sites in gp41. for each mutation, asparagine (n) in the canonical n-x-s/t recognition sequence for carbohydr ... | 2008 | 18829751 |
| personality and serotonin transporter genotype interact with social context to affect immunity and viral set-point in simian immunodeficiency virus disease. | from the beginning of the aids epidemic, stress has been a suspected contributor to the wide variation seen in disease progression, and some evidence supports this idea. not all individuals respond to a stressor in the same way, however, and little is known about the biological mechanisms by which variations in individuals' responses to their environment affect disease-relevant immunologic processes. using the simian immunodeficiency virus/rhesus macaque model of aids, we explored how personalit ... | 2008 | 17719201 |
| memantine upregulates bdnf and prevents dopamine deficits in siv-infected macaques: a novel pharmacological action of memantine. | n-methyl-d-aspartate (nmda) receptor activation is involved in the pathogenetic cascades of neurodegenerative disorders including human immunodeficiency virus (hiv) dementia. memantine, an uncompetitive nmda receptor antagonist, which has been recently approved for the treatment of alzheimer's disease, is being discussed as a potential adjunctive therapeutic substance for hiv dementia. we used simian immunodeficiency virus-infected rhesus macaques to assess the effects of memantine on brain dysf ... | 2008 | 17971830 |
| disruption of excitatory amino acid transporters in brains of siv-infected rhesus macaques is associated with microglia activation. | glutamate-mediated neurodysfunction in human immunodeficiency virus (hiv) infection has been primarily suggested by in vitro studies. the regulation of glutamatergic neurotransmission in inflammation is a complex interaction between activation of immune mediators and adaptive changes in the functional elements of the glutamatergic synapse. we have used simian immunodeficiency virus (siv)-infected macaques to answer the questions (i) whether perturbation of glutamate neurotransmission is evident ... | 2008 | 17986224 |