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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Until recently, chimpanzees were considered susceptible to human immunodeficiency virus type 1 (HIV-1) infection, but refractory to disease induction based on the asymptomatic status of all experimentally infected chimpanzees after over 10 years postinfection (PI). However, a decline in peripheral CD4+ T cells was noted in one chimpanzee (C499) of the Yerkes cohort of HIV-1 infected apes, after 11 years PI concurrent with increasing plasma viral load. These clinical signs were followed by the occurrence of opportunistic infections, thrombocytopenia, and progressive anemia leading to euthanasia. A second chimpanzee (C455) was transfused with blood from C499 collected during the symptomatic stage. Shortly thereafter, this second animal showed a rapid decline in peripheral CD4+ T-cell levels and sustained high viral load. Hematological analyses showed a 50% decrease in CFU-GM for both apes during the symptomatic phase and a reduction of 40% and 73% of the total CFU despite normal levels of CD34+ cells in the bone marrow. Cryopreserved sequential PBMC samples from these two chimpanzees were analyzed for constitutive and PHA-P induced levels of cytokines and chemokines. Data show that whereas there were no detectable constitutive levels of mRNA coding for IL-2, 4, and 10, there appears to be a transient increase in IFN-gamma message level coincident with increased viremia and this IFN-gamma synthesis decreased with disease progression. PHA-induced cytokine mRNA analysis showed low or undetectable levels of IL-4 and IL-10 mRNA in all samples and a marked decrease in the levels of IL-2 shortly after HIV infection. In addition, there was also a gradual decrease in IFN-gamma mRNA with progression of disease. Of interest were the findings of high to normal levels of PHA-induced synthesis of the chemokines MIP-1alpha, MIP-1beta, and RANTES in samples during the asymptomatic and early symptomatic period, which also dramatically decreased at late stages of the disease. These data suggest important roles for IL-2, IFN-gamma, and the chemokines in the regulation of immune responses in HIV-1-infected chimpanzees.
J Med Primatol
PMID:Immune and hematopoietic parameters in HIV-1-infected chimpanzees during clinical progression toward AIDS. 927 Nov 84

An apparent species-specific relatedness of SIVagm suggests a coevolution with their natural hosts. However, the exact species or subspecies classification of African green monkeys, AGM, is uncertain because current classification schemes rely on phenotype markers, while more definitive genetic data are lacking. In this study, the CD4 protein involved in tissue type recognition was genetically cloned and sequenced from PBMC RNA from all AGM species, including Barbados green monkeys (BGM). Phylogenetic trees were constructed that also included genomic CD4 nucleotide sequences from patas, sooty mangabeys, rhesus and pig-tail macaques, chimpanzees, and humans. Chimpanzees and humans consistently clustered together. Monkeys within the Cercopithecus genus formed a separate cluster which included pata monkeys, supporting its grouping as a member of Cercopithecus. Surprisingly, sooty mangabeys were genetically more closely related to Asian macaques than to other African species, which might explain why macaques are more susceptible to infection by the SIVsm group than to infection by SIVagm or HIV-1 and why patas, on the other hand, are highly susceptible to SIVagm infection. Based on CD4 genetic data, tantalus, vervets, grivets, and sabaeus formed separate subgroups with BGM grouping closely with vervets. The branching order of the AGM species was related to that of their respective SIVagm env sequences. The study suggests a strong correlation between CD4 phylogeny and the susceptibility of the host species to infection by a specific lentivirus and supports the assumption of a coevolution of SIVagm and AGM. CD4 sequencing is suggested as a relevant method for genetic determination of primate species.
J Med Primatol 1997 Jun
PMID:Relation between phylogeny of African green monkey CD4 genes and their respective simian immunodeficiency virus genes. 937 78

Immune responses mediated by CD8+ lymphocytes have been correlated with protection from HIV infection and disease progression in humans and nonhuman primates. The CD8+ cell population is heterogeneous in terms of biological function and phenotype. We have undertaken a review of the current state of knowledge of subtypes of CD8+ cells and their role in immune responses directed to HIV and related primate lentiviruses. Differences in the pathogenesis of lentivirus infections in various primate hosts were examined and the possible roles of the various subpopulations of CD8+ lymphocytes in the resistance and/or susceptibility to lentivirus-related disease were compared.
J Med Primatol 1997 Jun
PMID:CD8+ cell-mediated immune responses: relation to disease resistance and susceptibility in lentivirus-infected primates. 937 79

A number of rhesus macaques experimentally infected with SIV isolates such as SIVmac251, fail to seroconvert, develop high plasma viremia and die rapidly (within 6-7 months p.i.). We hypothesized that such rapid progression is a result of a state of hyperimmune activation and concomitant immune suppression of these animals at the time of virus challenge. In efforts to test the hypothesis that immune activation leads to rapid progression of lentivirus-induced disease, adult rhesus macaques were infected with SIV mac251 and received an alternate monthly schedule of repeated immunization with allogeneic cells, keyhole limpet hemocyanin and tetanus toxoid (group I). For purposes of controls, a group of monkeys was infected with the same pool and dose of virus but were not immunized (group II) and a group was immunized with the same schedule of multiple antigens as group I but were not infected with SIV (group III). All the animals in group I (n = 3) either failed to seroconvert or developed very low levels of SIV antibodies, had high plasma p27 defined antigenemia, and died within 8 months (2/3 died within 4 months). Of the animals in group II (n = 8), two patterns emerged as we had noted before. One subgroup (3 animals), displayed the same profile as group I (failure to fully seroconvert, high p27 levels and death by 8 months), whereas the other subgroup (5 animals) seroconverted, had low plasma p27 levels, and survived past 11 months (2/5 still alive past 22 months). All 3 animals in group III remained healthy. The data provided herein suggest that either experimental or natural (due to factors not clear at present) immune stimulation may lead to accelerated lentivirus induced disease progression most likely due to immune suppression and has implications for the understanding of the mechanisms for the rate of disease progression in human HIV-1 infection.
J Med Primatol 1997 Aug
PMID:Immune stimulation may contribute to enhanced progression of SIV induced disease in rhesus macaques. 941 68

The dichotomy of type-1 and type-2 T-helper (Th) immune responses is thought to be an obstacle to develop Human immunodeficiency virus-type- (HIV-1) vaccines capable of inducing effective cellular as well as humoral immune responses. Macaca mulatta were immunized using two different HIV-1sf2 envelope vaccine strategies, based on either immune-stimulating complexes (ISCOM) or chimeric Fowlpox (FP) vaccines. One month following the third immunization all animals were heterologously challenged with simian/human immunodeficiency virus (SHIVsf13). Vaccinated monkeys, which were protected had the highest levels of both type-1 and type-2 HIV-1 specific T-helper cell (Th) responses in addition to the highest homologous and heterogenous virus neutralizing antibodies. To determine how long Th responses persisted and if they correlated with protection, animals were rechallenged after waiting for four months without re-boosting. Macaques which maintained the highest gp120-specific type-1 (IFN-gamma) responses were protected, while there was evidence of viral clearance in two others. These findings demonstrate the importance of both or mixed type-1 and type-2 Th responses in HIV-1 vaccine induced immunity while suggesting a possible role of persistent type-1 responses in maintaining protective immunity over time.
J Med Primatol
PMID:The role of type-1 and type-2 T-helper immune responses in HIV-1 vaccine protection. 974 43

By animal to animal passage in rhesus and pig-tailed macaques, we developed a rhesus model of HIV-1 disease in humans. Rhesus macaques infected with a cell-free stock of SHIVKU-2 developed CD4+ T cell loss, primary lentiviral encephalitis and pneumonia, and AIDS. Six of nine rhesus macaques died within eight months post-inoculation, while the remaining three are at five, five, and eight months post-inoculation, respectively. Animals infected by either mucosal or parenteral routes of infection had a similar course of infection.
J Med Primatol
PMID:Chimeric SHIV that causes CD4+ T cell loss and AIDS in rhesus macaques. 974 44

We have compared nef gene sequences isolated by PCR from peripheral blood lymphocyte DNA of macaques which had been inoculated with either biologically or molecularly cloned SIV(Mne). Two samples from each animal obtained either early after infection (week 2-8) or after significant CD4+ depletion (week 21-137) were analyzed. Three substitutions in the predicted Nef amino acid sequence were seen in all animals at the late time point, and two more in all but one. Two of the common exchanges are located about 40 residues apart in the Nef core sequence, but are in proximity on the tertiary structure as judged by computer modelling using the structure of the HIV Nef core protein as a guide. Most recurring in vivo changes replaced a residue found in the cloned Nef sequence with one present in a consensus derived by aligning the Nef sequences of the SIVsm/HIV-2 groups. Animals inoculated with virus already containing the "late version" nef gene developed a more aggressive disease. The macaque adapted (MA)nef conferred a threefold higher infectivity to the cloned virus, but had no effects on CD4 downregulation. Propagation of virus with MAnef in tissue culture resulted in the rapid emergence of variants with newly attenuated nef. These findings suggest that the selective pressure on nef in vivo and in vitro are different.
J Med Primatol
PMID:Sequence diversity of SIV(Mne) Nef in vivo and in vitro. 974 46

The macaque/SIV animal system is an important model for studying AIDS pathogenesis and for evaluating the efficacy of vaccines and anti-viral therapeutics. However, differences between HIV-1 and SIV envelope proteins exist that render the SIV/macaque model of limited value when examining envelope determinants of retroviral pathogenesis. To overcome this problem, we utilized a chimeric virus, SHIV(SF33), containing the env gene from HIV-1SF33 in the context of the molecular clone SIVmac239, in the macaque animal model. In this study SHIV(SF33A), a pathogenic virus that evolved in vivo from a rhesus macaque infected intravenously with the molecular clone SHIV(SF33) was used in both in vitro and in vivo studies. By using a cell culture system, we examined the biological properties of our parental and animal-adapted chimeric viruses and compared in vitro susceptibility to in vivo studies.
J Med Primatol
PMID:In vitro infection of primate PBMC with simian/human immunodeficiency virus, SHIV(SF33A): correlation to in vivo outcome. 974 47

Various stages in the lifecycle of HIV-1 were investigated in Macaca nemestrina and humans in vitro. Early events were analyzed by end point dilution DNA PCR with HIV-1 and SHIV infected PBMCs, while p24 and p27 ELISA assays were used to analyze core antigen production from infected cells. The results demonstrate that a step in the virus life cycle, beyond reverse transcription is blocked for HIV-1 infection in macaque cells.
J Med Primatol
PMID:In vitro HIV-1 infection in Macaca nemestrina PBMCs is blocked at a step beyond reverse transcription. 974 50

In a prior report, we described the isolation and characterization of SIVrcm, a distinct primate lentivirus found in a household pet Red-Capped Mangabey (RCM) in Gabon. SIVrcm is divergent from HIV-1 and HIV-2/SIV families of primate lentiviruses. In this report, additional in vitro replication studies and the results of SIVrcm infection in macaques are presented. SIVrcm causes little cytopathic effedct in Molt 4 Clone 8 cells and in rhesus and human PBMCs. In vivo, SIVrcm is non-pathogenic after 200 days in rhesus macaques and after one year in cynomolgous macaques, but does cause a chronic infection in both macaques.
J Med Primatol
PMID:SIVrcm infection of macaques. 974 49


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