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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the early pathogenesis of infection by molecular clone 1.9 of SIVsmmPBj14 in pig-tailed and cynomolgus macaques. Like the uncloned PBj14 parent, SIVsmmPBj14-1.9 consistently induced an acute clinical syndrome characterized by behavioral depression, fever, profuse diarrhea, dehydration, lymphadenopathy, splenomegaly, and mucocutaneous exanthema that began at 7 days postinfection (DPI). The acute clinical disease coincided with a marked cell-associated and cell-free viremia, during which SIV p27 was demonstrated in 4 to 68% of circulating mononuclear leukocytes between 4 and 17 DPI. Also characteristic were monocytosis and reductions in CD4+ and CD8+ T lymphocytes, as well as CD20+ B lymphocytes. The most profound depletion occurred in the CD44hi subset of CD4+ T cells. Unlike animals infected previously with uncloned or biologically cloned PBj14, however, all SIVsmmPBj14-1.9-infected macaques survived the acute-phase disease to progress to a chronic, largely asymptomatic phase of infection. Recovery from the acute-phase disease correlated with down modulation of virus replication and the appearance of antibodies to SIV Env and Gag proteins. Similar to the PBj14 parent, PBj14-1.9 targeted to intestine, spleen, bone marrow, lymph node, and cerebellum. Saliva contained substantial quantities of infectious virus and no viral antibodies during the early phase of infection. By contrast, saliva from chronically infected animals usually contained antibodies but no virus. This study extends previous work demonstrating that the acute clinical syndrome produced by SIVsmmPBj14 in pig-tailed macaques represents a unique model of lentiviral pathogenesis.
AIDS Res Hum Retroviruses 1993 Mar
PMID:Early pathogenesis of disease caused by SIVsmmPBj14 molecular clone 1.9 in macaques. 847 19

The gag-homologous region of the human endogenous retrovirus K10 (HERV-K10) was amplified by PCR from human genomic DNA and was analyzed by DNA cloning, sequencing, and expression of open reading frames in the prokaryotic pATH expression system. The analysis of genomic DNA of three donors provided evidence that HERV-K10 genes contain an open reading frame of 1966 bp spanning the entire gag-homologous region. In the prokaryotic system the entire reading frame of the HERV-K10 gag gene could be expressed as a fusion protein exhibiting a molecular weight of about 110,000. In addition, when the gag-homologous region and the adjacent HERV-K10 protease gene were prokaryotically expressed, we observed a Gag-protease fusion protein that exhibited specific autoproteolytic activities and processing of HERV-K10 Gag protein. By introducing deletions on the right end of the putative protease gene an autocatalytic site could be localized within 300 bp of the putative HERV-K10 protease gene. For the first time, these results provide evidence that the HERV-K10 encodes a full-length Gag protein and a functional protease.
AIDS Res Hum Retroviruses 1993 Apr
PMID:Human endogenous retroviral element K10 (HERV-K10) encodes a full-length gag homologous 73-kDa protein and a functional protease. 851 50

In view of the growing evidence that virus-specific cytotoxic T lymphocytes (CTL) play an important role in containing the early spread of human immunodeficiency virus type 1 (HIV-1) in infected individuals, novel vaccine strategies capable of eliciting HIV-1-specific CTL are being pursued in attempts to create an effective AIDS vaccine. We have used the simian immunodeficiency virus of macaques (SIVmac)/rhesus monkey model to explore the induction of AIDS virus-specific CTL responses by DNA vaccination. We found that the inoculation of rhesus monkeys with plasmid DNA encoding SIVmac Env and Gag elicited a persisting SIVmac-specific memory CTL response. These CTL were CD8+ and major histocompatibility complex class I restricted. These studies provide evidence for the potential utility of DNA inoculation as an approach to an HIV-1 vaccine.
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PMID:Simian immunodeficiency virus-specific cytotoxic T-lymphocyte induction through DNA vaccination of rhesus monkeys. 852 93

MHC class I-restricted CTL play an important role in limiting the spread of HIV-1 in the infected individual. Elucidating the molecular interactions of CTL with the virus is, therefore, of central importance for characterizing the immune control of this infection. In exploring this CTL response, we have defined the TCR usage by SIVmac Gag-specific CTL in rhesus monkeys. Thirty-nine CTL clones were generated from PBL of three SIVmac-infected monkeys expressing the MHC class I Mamu-A*01 gene product, all of which were shown to recognize a single SIVmac Gag peptide in association with Mamu-A*01. Sixty-six percent of CTL clones derived from two monkeys early after infection expressed TCR genes of the V beta 13 family; 70% of these V beta 13+ CTL clones expressed a TCR heterodimer composed of V alpha 1 and V beta 13 gene products. In addition, there appeared to be a selection of a single conserved amino acid and restricted CDR3 lengths in junctional regions of TCR beta-chains expressed by the V beta 13+ CTL clones. These findings indicate significant structural constraints on the CTL-TCR interaction with the AIDS virus. Interestingly, 55% of the CTL clones derived from the third animal at a later time following infection employed genes of the V beta 6 family in their TCR. Despite the preferential use of TCR V family genes by the CTL clones, the SIVmac Gag-specific CTL response was clearly polyclonal; TCR expressed by these CTL clones displayed varied sequences in their CDR3 regions. Other V gene families, including V beta 23, V alpha 8, and V alpha 20, were used in TCR expressed by SIVmac Gag-specific CTL clones. These studies, therefore, indicate that the TCR repertoire of SIVmac Gag-specific CTL that share a peptide and MHC class I recognition specificity can be diverse. Such a broad CTL-TCR repertoire may be advantageous for the host in containing an AIDS virus infection.
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PMID:The T cell receptor gene usage by simian immunodeficiency virus gag-specific cytotoxic T lymphocytes in rhesus monkeys. 856 49

HIV-1 Gag protein precursor p55, and its processed products, p17, p24, and p15 were overproduced in Escherichia coli and purified to near homogeneity. To study the antigenic properties and the potentiality as the diagnostic and prognostic reagents, varying amounts of the purified Gag proteins were dotted onto the polyvinylidene difluoride membrane and reacted with 40 sera of HIV-1-infected individuals (35 AC, 1 ARC, and 4 AIDS patients) and 10 sera of normal healthy donors. p55 reacted with 40 (100%) sera of HIV-1 carriers, while p17, p24, and p15 reacted with 37 (92.5%), 35 (87.5%) and 34 (85%) of the 40 sera of HIV-1 carriers, respectively. On the whole, the reaction of p55 was especially strong and that of p15 was the weakest. p55 showed the strongest reaction among the four Gag proteins with all specimens, and it showed a positive reaction with a carrier serum with which none of the processed Gag proteins showed a positive reaction. Therefore, p55 is the most useful antigen among the four Gag proteins for detection of the Gag antibodies and may even be one of the most useful antigens for the diagnosis of HIV-1 infection.
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PMID:Overproduction, purification, and diagnostic use of the recombinant HIV-1 Gag proteins, the precursor protein p55 and the processed products p17, p24, and p15. 856 32

We report here the use of the highly attenuated SIVmac142 clone, unable to establish permanent infection of rhesus macaques, in a vaccine trial. Four rhesus macaques were immunized over a long time period with HUT-78 cells infected with wild-type SIVmac142 or, in order to reinforce the safety use of the vaccine, a deleted mutant with similar in vitro infectivity. The first two injections were done with living cells and the remaining boosts with cells emulsified in muramyl dipeptide adjuvant. Three control macaques were injected with uninfected HUT-78 cells. Over 3 years, we have been unable except once to detect viral infections by three methods. However, antibodies directed against the viral Gag proteins and envelope glycoproteins were detected by immunoblots and/or in vitro neutralization assays. All macaques were challenged intravenously with a low dose (10 animal infectious doses) of a highly pathogenic biological clone of SIVmac251 grown on macaque PBMCs. All seven animals became persistently viremic following challenge. The cell-associated viral loads of the vaccinated monkeys were not reduced relative to those of unvaccinated controls during the first weeks postchallenge even if vaccinated monkeys did not present a transient CD4 decrease. Thus, our data reinforced the notion that the efficacy of live attenuated SIV requires the establishment of persistent infection.
AIDS Res Hum Retroviruses 1995 Nov
PMID:Highly attenuated SIVmac142 is immunogenic but does not protect against SIVmac251 challenge. 857 98

During 1984-92, in South Africa, virologists isolated HIV-1 from HIV/AIDS patients at hospitals in the Western Cape. Two virologists from the University of Stellenbosch Hospital in Tygerberg selected 22 virus strains, belonging to HIV-1 subtypes B, C, and D, to study in order to develop a specific and sensitive polymerase chain reaction (PCR) protocol using env, gag, and LTR primers. They used five different primer pairs to prepare cell lysates from the HIV-infected cultured cells: gag SK38/SK39, gag 22/SK39, gag a/b, gag c/d (nested), env SK68/SK69, and LTR SK29/SK30. The virologists evaluated eight different PCR profiles: one profile each for the three gag primer pairs, three profiles for the env, and two profiles for the LTR primer pairs. They changed the number of PCR cycles, time per cycle, and/or annealing temperature in each profile. The PCR profile for a specific primer pair that detected one copy of proviral plasmid DNA after dot-blot hybridization was considered the optimum PCR profile. Gag primer pairs detected HIV-1 DNA in all 22 samples. The env primer pair did not detect most HIV-1 subtype C samples. When the researchers increased the number of cycles and time per cycle, the env primer pair achieved 100% sensitivity. When they decreased the annealing temperature and increased the individual cycle times, the LTR primer pairs detected all samples. These findings support that optimization of a PCR assay is necessary to achieve high assay sensitivity, specificity, and reproducibility and that PCR sensitivity should be considered seriously when interpreting PCR results for HIV diagnosis.
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PMID:Detection of southern African human immunodeficiency virus type 1 subtypes by polymerase chain reaction: evaluation of different primer pairs and conditions. 860 4

To clarify the physiological function of two zinc finger motifs in the nucleocapsid (NC) domain of the Gag protein of human immunodeficiency virus type 1 (HIV-1), we changed cysteine to serine in either of the two motifs or both by site-directed mutagenesis. Viral infectivity was lost by any of the mutations, but their effects appeared differently in the respective mutants. Northern blot analysis showed that the first finger mutant was far less efficient (approximately 10% of the wild type) in genomic RNA encapsidation and that the dual mutant of both fingers completely failed to encapsidate the RNA. In contrast, the second finger mutant retained its ability for RNA encapsidation with an efficiency similar to that of the wild type. Immunoblot analysis of the lysates of CD4-positive M8166 cells transfected with the mutant proviral DNAs showed that the processing of Gag precursors was delayed in two mutant viruses having alterations in the first finger sequence, whereas the processing of the second finger mutant appeared to be normal. On the other hand, immunoblot analysis of the virus particles showed that the second finger mutant particles contained some proteins that were thought to be degradation products of p24CA. Electron microscopic observation showed that all particles of these mutant viruses were morphologically alike except that they had a slightly larger diameter than that of the wild type. These results indicate that these finger motifs of HIV-1 NC protein do not function equivalently. Namely, the first finger is primarily responsible for RNA encapsidation and the second is required for stabilization of virus particles.
AIDS Res Hum Retroviruses 1996 Jun 10
PMID:Mutational analysis of two zinc finger motifs in HIV type 1 nucleocapsid proteins: effects on proteolytic processing of Gag precursors and particle formation. 873 31

HIV-1 subtype B isolates have previously been described in India only in the state of Andhra Pradesh, while subtype C isolates have been reported as widespread in the Bombay and Goa regions of India. Gag subtype was determined in HIV-1 isolates from six Indians and one Ethiopian. One Indian was a native of Goa residing in Kuwait, and the others were natives of Bihar, Haryana, West Bengal, and New Delhi states. Five subjects were males aged 20-26 years. The remaining two subjects were females aged 34 and 40. Four of the men acquired HIV through sexual transmission; the other man was presumably infected through contaminated blood. Six isolates were identified as subtype C and one as subtype B. These preliminary findings obtained by arranging the HIV-1 gag sequences according to their similarity score were confirmed by cladogram and nested analysis. HIV-1 subtype C isolates are therefore present in Bombay and Goa as well as in other regions of northern and eastern India. The subtype has also infected Indian and Ethiopian expatriates living in Kuwait.
AIDS Res Hum Retroviruses 1996 May 01
PMID:HIV type 1 subtypes B and C from new regions of India and Indian and Ethiopian expatriates in Kuwait. 874 90

In Dar es Salaam, Tanzania, health workers at Muhimbili Medical Centre collected serum and saliva samples from 135 HIV-positive persons attending the AIDS Clinical Trial Clinic, 130 people who came for voluntary HIV testing, and 60 hospital patients. Researchers aimed to assess the suitability of the Omni-SAL device in collecting saliva and the sensitivity, specificity, and feasibility of detecting HIV-1 IgG antibodies in saliva using GACELISA (an IgG capture ELISA) and Western blot assays. Laboratory personnel optimized Western blot for confirmatory testing of saliva specimens by using a biotin/avidin detection as suggested by McMahan and Hofman. All 135 patients attending the AIDS Clinical Trial Clinic, 8 (6.15%) people undergoing voluntary HIV testing, and 15 (25%) of hospital patients tested positive for HIV (total = 158). GACELISA detected all HIV-1 seropositive individuals and did not detect HIV-1 in any of the HIV-1 seronegative individuals (sensitivity 100%; specificity 100%). The saliva optical density to cut-off value for the HIV-1 seropositives was 5.26-9.82, indicating no ambiguity in the results. All saliva specimens on GACELISA reacted strongly to HIV-1 viral proteins Env, Pol, and Gag on the Western blot optimized for testing saliva specimens. It took more than 10 minutes to saturate the collecting pad (Omni-SAL) in 2% of individuals. Saturation of the collecting pad took less than 3 minutes in most cases (64%). Most individuals preferred saliva to be collected for HIV testing than serum and urine (65% vs. 23% and 12%, respectively). 96% of all individuals thought the Omni-SAL device to be easy. These findings suggest that saliva is an adequate specimen for screening and diagnosis of HIV infection. Since many saliva samples can be collected quickly, easily, and safely, Omni-SAL and GACELISA can be done under any field situation by people with minimal training.
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PMID:Detection of anti-HIV-1 IgG antibodies in whole saliva by GACELISA and Western blot assays. 875 29


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