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

Early work on the roles of cytotoxic T lymphocytes (CTLs) in acute viral infections in animal models showed that i) the clearance of virus coincided with the increase in CTL activity rather than specific antibody levels, ii) transfer of CTLs after infection could protect from a lethal dose of virus, and iii) in primed, compared to naive, animals, CTL activity appeared 1-3 days earlier after a challenge infection. There is now a series of findings with individuals who have been exposed to HIV but are HIV-seronegative that suggest a protective role for CTLs. Usually after in vitro culture, HIV-specific CTLs have been isolated from i) infants born of infected mothers, ii) long-time partners of HIV-infected people, iii) some prostitutes in Africa, and iv). Most recently, 7/20 seronegative health care workers exposed once to HIV have been shown to possess HIV env-specific CTLs. The findings suggest that CTLs (a type I T cell response) may rapidly clear a low dose of HIV. Experiments with SIV are proposed that may provide more direct supporting data for this possibility.
J Med Primatol 1996 Jun
PMID:Do cytotoxic T lymphocytes clear some HIV/SIV infections? 889 36

In this study, we report on the derivation of a pathogenic SIV-HIV chimeric virus (SHIV) and the initial characterization of the viral sequences from the first (macaque PPc) of a series of pig-tailed macaques that developed CD4+ T cell loss and AIDS. Viral genes were amplified by PCR from the brain, lymphoid, and kidney tissues and their sequences compared to the original SHIV used to initiate passages in macaques. Our results show that the vpu gene, which was nonfunctional in the original SHIV, now coded for functional protein in macaque PPc. The tat and rev genes had no consensus changes but the nef gene had 4-5 consensus changes, depending on the tissue examined. The gp 120 gene had the highest number of nucleotide and amino acid substitution rates that varied from 0.64% to 1.44% and 1.17% to 3.71%, respectively, again depending on the tissue examined. These results suggest that a constellation of changes accumulated at the genomic level during the derivation of a SHIV that was pathogenic for pig-tailed macaques.
J Med Primatol 1996 Jun
PMID:Initial characterization of viral sequences from a SHIV-inoculated pig-tailed macaque that developed AIDS. 889 38

Immunophenotype analysis was used to characterize circulating lymphocyte subset levels in both rhesus monkeys that were chronically infected with SIVmac239 and in those that had resisted SIVmac239 infection as a result of prior vaccination with an attenuated SIV strain. Alterations in T, NK, and B cell subsets were compared with those previously identified in humans chronically infected with HIV [8-11, 14, 22]. The well-known decrease in CD4+ cell levels was observed in the SIVmac239-infected animals. However, these animals had relatively little activation of circulating CD8+ T cells as compared with uninfected monkeys. This contrasts with chronically HIV-infected humans who have substantial activation of circulating CD8+ cells as evidenced by elevated HLA-DR and CD38 antigen expression on CD8+ cells as well as substantially increased percentages and numbers of total CD8+ cells. NK cells of the SIVmac239-infected animals, on the other hand, demonstrated the same changes recently described in HIV-infected humans, i.e., a decrease in circulating percentages and a decreased amount of FcRIII (CD16). B cell percentages were markedly increased in the SIVmac239-infected animals, a finding also noted in some children with HIV infection but not in HIV-infected adults. SIV delta nef-vaccinated/SIVmac239-challenged animals showed none of the immune alterations found in the SIVmac239-infected monkeys, providing further confirmation of lack of SIV disease in these vaccinated animals.
J Med Primatol 1996 Jun
PMID:The immunopathogenesis of retroviral diseases: no immunophenotypic alterations in T, B, and NK cell subsets in SIVmac239-challenged rhesus macaques protected by SIV delta nef vaccination. 889 39

Stable introduction of therapeutic genes into hematopoietic stem cells has the potential to reconstitute immunity in individuals with HIV infection. However, many important questions regarding the safety and efficacy of this approach remain unanswered and may be addressed in a non-human primate model. To facilitate evaluation of expression of foreign genes in T cells derived from transduced hematopoietic progenitor cells, we have established a culture system that supports the differentiation of rhesus macaque and human CD34+ bone marrow derived cells into mature T cells. Thymic stromal monolayers were prepared from the adherent cell fraction of collagenase digested fetal or neonatal thymus. After 10-14 days, purified rhesus CD34+ bone marrow-derived cells cultured on thymic stromal monolayers yielded CD3+CD4+CD8+, CD3+CD4+CD8-, and CD3+CD4-CD8+ cells. Following stimulation with mitogens, these T cells derived from CD34+ cells could be expanded over 1,000-fold and maintained in culture for up to 20 weeks. We next evaluated the ability of rhesus CD34+ cells transduced with a retroviral vector containing the marker gene neo to undergo in vitro T cell differentiation. CD34+ cells transduced in the presence of bone marrow stroma and then cultured on rhesus thymic stroma resulted in T cells containing the retroviral marker gene. These studies should facilitate both in vitro and in vivo studies of hematopoietic stem cell therapeutic strategies for AIDS.
J Med Primatol 1996 Jun
PMID:In vitro T lymphopoiesis: a model system for stem cell gene therapy for AIDS. 889 40

We explored the relationship between T cell activation signals and dendritic cells (DC) in the replication cycle of immunodeficiency viruses. First we analyzed the effect of two cell cycle inhibitors (mimosine and aphidicolin) on SIV reverse transcription, circularization, and integration in macaque resting T cells stimulated with anti-CD3 mAb at the time of infection. The formation of SIV LTR circles was blocked by the G1 inhibitor mimosine. The G1/S inhibitor aphidicolin neither affected circularization nor integration of SIV DNA. Therefore, the induction of SIV LTR circle production is likely to be mediated by signaling events normally regulating the G1 to S transition. We further characterized DC-dependent HIV-expression in human T cells. We examined the effect of ligating two novel receptors, IPO-3 and Bgp95, on DC-dependent HIV-1 expression. Activation of DCs through IPO-3 receptors, and to a lesser extent Bgp95 ligation, upregulated HIV spread in these cells. The mechanisms by which IPO-3 vs. Bgp95 increase HIV-1 levels appear to be different. In particular, IPO-3 ligation alone on T cells also increased HIV-1 levels. Activation of T cells via defined surface receptors or with DCs is required for establishing HIV/SIV cDNA synthesis in T cells.
J Med Primatol 1996 Jun
PMID:Immunodeficiency virus cDNA synthesis in resting T lymphocytes is regulated by T cell activation signals and dendritic cells. 889 41

One of the manifestations of human HIV-1 and nonhuman primate SIV infection that lead to disease is reasoned to be secondary to generalized T-cell dysfunction. The molecular mechanisms associated with the T-cell dysfunction remain to be elucidated. To address this issue, we sought to utilize the nonhuman primate model to study intracellular signaling events in cells from disease-susceptible rhesus macaques and disease-resistant sooty mangabeys. Because relatively little is known about these events in nonhuman primates, our laboratory defined optimal conditions, reagents, and assays for the study of signal transduction events in cells from nonhuman primates. The protein phosphorylation patterns in the two monkeys exhibited quantitative, qualitative, and kinetic differences. Antibodies to Stat6 detected a unique band in macaque cell lysates. This band is markedly decreased human cell lysates and never seen in mangabey cell lysates. Detection of various other intracellular signaling proteins is also described.
J Med Primatol 1996 Jun
PMID:Detection of intracellular signal transduction molecules in PBMC from rhesus macaques and sooty mangabeys. 889 42

The lack of a representative animal model that permits frequent in utero fetal blood sampling is a major limiting factor for the study of maternal-fetal HIV transmission. Therefore, we have developed a maternal-fetal virus infection model using chronically catheterized macaques to simultaneously study the time-course of viral infection in the mother and the response of the fetus to maternal HIV infection. Pregnant macaques were infected with 10(3) infectious units of HIV-2(287); every 3 days blood samples from both the mother and the fetus as well as amniotic fluid samples were collected. We found a varying degree of peak and time-to-peak virus load, virus-infected PBMCs, and free virus (determined by QC-RNA-PCR method) in maternal blood. Two of the three mothers with more than 10(8) copies of viral RNA/ml of plasma at peak viremia transmitted the virus to their fetuses at about 14 days post-infection. As observed with HIV-2(287) infected mothers, virus-infected fetuses also produced a rapid rate of CD4+ cell decline in utero.
J Med Primatol 1996 Jun
PMID:Development of a chronically catheterized maternal-fetal macaque model to study in utero mother-to-fetus HIV transmission: a preliminary report. 889 43

The SIV-infected macaque provides an excellent model to study factors involved in maternal-fetal transmission of HIV. In our prenatal transmission studies, female macaques were inoculated intravenously during midgestation with either SIV/DeltaB670 or a combination of SIV/ DeltaB670 and the macrophage-tropic molecular clone SIV/17E-Fr. The females harbored a genetically diverse virus population at parturition, whereas a single genotype from the maternal quasispecies was identified in the infants. One of two variants was transplacentally transmitted to the infants, SIV/17E-Fr or B670-Cl 12, a genotype contained within the SIV/ DeltaB670 inoculum. Both of these variants have been identified in the central nervous system of macaques that have developed encephalitis and they replicate in vitro on primary rhesus macrophages. These results suggest a critical role for macrophages in fetal infection in utero. In our perinatal transmission studies we have evaluated the viral genotypes found in two newborn macaques infected orally with SIV/DeltaB670 and in one infant infected via amniotic inoculation in late gestation. More than one viral genotype was identified in each infant, moreover, each infant harbored different genotypes. These results suggest different mechanisms are responsible for viral infection via these routes.
J Med Primatol 1996 Jun
PMID:Genotypic analysis of infant macaques infected transplacentally and orally. 889 44

The Accell gene delivery system (gene gun) was used to deliver gold particles coated with HIV-1LAI and SIVmac239 expression constructs into the epidermis of rhesus macaques, resulting in the elicitation of env- and gag-specific humoral responses. One microgram of vector DNA per dose was sufficient to induce immune responses in monkeys using SIVmac239 gp160 and gp120 vectors driven by the CMV-intron A promoter. Several parameters, including the identity of the vector, the length of the rest period between immunizations, the number of immunizations, and the amount of DNA per immunization, are all important in designing an optimal DNA immunization regimen. In addition, gene gun-based DNA immunization using low efficiency expression vectors is an effective means of priming for the induction of vigorous antibody responses in macaques following boosting with recombinant subunits.
J Med Primatol 1996 Jun
PMID:Induction of immunodeficiency virus-specific immune responses in rhesus monkeys following gene gun-mediated DNA vaccination. 889 45

An effective immune response involves the specific recognition of and elimination of an infectious organism at multiple levels. In this context DNA immunization can present functional antigenic proteins to the host for recognition by all arms of the immune system, yet provides the opportunity to delete any genes of the infectious organism which code for antigens or pieces of antigens that may have deleterious effects. Our group has developed the use of nucleic acid immunization as a possible method of vaccination against Human immunodeficiency virus type 1 (HIV-1) [1,2,3,10,11,12]. Sera from non-human primates immunized with DNA vectors that express the envelope proteins from HIV-1 contain antibodies specific to the HIV-1 envelope. These sera also neutralize HIV-1 infection in vitro and inhibit cell to cell infection in tissue culture. Analysis of cellular responses is equally encouraging. T cell proliferation as well as cytotoxic T cell lysis of relevant env expressing target cells were observed. In addition, evidence that DNA vaccines are capable of inducing a protective response against live virus was demonstrated using a chimeric SIV/HIV (SHIV) challenge in vaccinated cynomologous macaques. We found that nucleic acid vaccination induced protection from challenge in one out of four immunized cynomolgus macaques and viral load was lower in the vaccinated group of animals versus the control group of animals. These data encouraged us to analyze this vaccination technique in chimpanzees, the most closely related animal species to man. We observed the induction of both cellular and humoral immune responses with a DNA vaccine in chimpanzees. These studies demonstrate the utility of this technology to induce relevant immune responses in primates which may ultimately lead to effective vaccines.
J Med Primatol 1996 Jun
PMID:In vivo protective anti-HIV immune responses in non-human primates through DNA immunization. 889 46


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