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

Fine structure and antigenic make-up analysis of HIV were combined in a 2D model, from which functional aspects can be deduced. On the envelope 72 probably trimeric surface knobs (gp120) are connected to the virion via the transmembrane protein gp41. Gp120 is shed during ageing of the virion, but host cell antigens stay firmly anchored to the envelope. Underneath the envelope, p17 forms the matrix protein layer, while the capsid of the double cone shaped core is built up of p24. The relation between biochemical findings and morphogenesis and maturation of HIV as well as aspects of pathogenesis and vaccination are discussed.
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PMID:Morphogenesis and morphology of HIV. Structure-function relations. 266 84

The gag proteins of human retroviruses such as human immunodeficiency virus (HIV-1) are specifically myristoylated in their amino termini (1, 2, 3). N-myristoyl glycinal diethylacetal (N-Myr-GOA) and other N-Myr-compounds (N-Myr-Gly-GOA, N-Myr-Gly-Gly-GOA and N-Myr-Gly-Gly-Gly-GOA) were newly synthesized and investigated for activity of antimyristoylation of these gag proteins and for influence on viral replication. Of the N-Myr-compounds tested, N-Myr-GOA most severely inhibited the protein myristoylation; N-Myr-Gly-GOA also inhibited it, but moderately. Furthermore, it was observed that N-Myr-GOA at 20 microM caused noticeable inhibition (about 80%) of the production of mature HIV in the HIV-1-infected MT-4 cells. In this system, N-Myr-GOA substantially inhibited more than 90% of the N-myristoylation of p17 gag protein produced in the HIV-1-infected MT-4 cells. These results suggest that the N-myristoylation of p17 gag protein of HIV-1 may be essential in its structural assembly or maturation.
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PMID:Antimyristoylation of the gag proteins in the human immunodeficiency virus-infected cells with N-myristoyl glycinal diethylacetal resulted in inhibition of virus production. 269 61

The virally encoded protease of human immunodeficiency virus is responsible for the processing of the gag and gag-pol polyprotein precursors to their mature polypeptides. Since correct processing of the viral polypeptides is essential for the production of infectious virus, HIV protease represents a potential target for therapeutic agents that may prove beneficial in the treatment of AIDS. In this study, full-length gag polyprotein has been synthesized in vitro to serve as a substrate for bacterially expressed HIV-1 protease. Expression of the protease in E. coli from the lac promoter was enhanced approximately five-fold by deletion of a potential hairpin loop upstream from the codon determining the amino terminus of mature protease. Extracts of induced cultures of E. coli harboring a protease-containing plasmid served as the source of protease activity. The gag polyprotein synthesized in vitro was cleaved by such lysates, producing fragments corresponding in size to p17 plus p24 and mature p24. Immunoprecipitations with monoclonal antibodies to p17 and p24 polypeptides suggest that initial cleavage of gag polyprotein occurs near the p24-p15 junction. The proteolysis was inhibited by pepstatin with an IC50 of 0.15 mM for cleavage at the p24-p15 junction and 0.02 mM for cleavage at the p17-p24 junction.
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PMID:Cleavage of HIV-1 gag polyprotein synthesized in vitro: sequential cleavage by the viral protease. 269 58

Intrathecal antibody responses to HIV were investigated by a highly sensitive immunoblot assay. Serum and CSF specimens were tested for reactivity with the recombinant HIV gag proteins p15, p17 and p24 and with the recombinant transmembrane protein p41. Autochthonous production of virus-specific IgG to one or more HIV structural proteins was seen in 8 of 10 asymptomatic seropositive subjects, in 3 of 4 men with AIDS-related complex, and in 9 of 13 patients with AIDS. These results were consonant with an elevated CSF/serum antibody ratio to total HIV antigen. The high frequency of local HIV-specific antibody synthesis in seropositive individuals without related clinical symptoms indicates an early involvement of the CNS in HIV infections.
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PMID:Analysis of oligoclonal antibody bands against individual HIV structural proteins in the CSF of patients infected with HIV. 270 64

Between May 1986 and April 1987 routine screening for anti-HIV antibody was performed by enzyme immunoassay (EIA) on 3344 serum samples. The 1160 samples found positive or borderline were further analysed in Western blot (Wb). We analysed the frequency of different patterns of 'intermediate' Wb reactions (1-3 'specific' bands) and tried to determine their significance by searching for possible modifications of the pattern of reaction a few months later. Of 1160 Wb, 461 were clearly positive, 489 negative and 210 'intermediate'. The latter consisted of: 92 sera with anti-p24 (associated or not), 23 with anti-gp 120 and 160, 16 with anti-p55, 12 with anti-p41, 10 with anti-p65, eight with anti-p17 and four with anti-p31. A non-specific pattern was observed in the remaining 45. Of these sera, 46% were obtained from high risk subjects, 38% from persons without risk and in 16% no reliable information was available. In 30 subjects (24 with p24 and 6 with p41), a second sample was obtained about three months later. The reaction persisted in nine, was replaced by another in five, and disappeared in 15. One subject with anti-p41 in the first sample became clearly positive. In one of the 15 samples with disappearance of the reaction, the antigen p24 was present as the only sign of HIV infection. Later samples of this subject showed clear seroconversion. In many subjects with and without risk of exposure to HIV, the Wb gives an intermediate pattern of reactions (1-3 specific bands), that does not permit definitive conclusion on one single sample. Later controls are therefore necessary. Most of these reactions do not correspond to HIV infection.
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PMID:Serological diagnosis of HIV infection: incidence, outcome and significance of partial reactions found in western blot analysis. 275 92

Serum specimens (n = 6,045) obtained from 3,207 Protestant missionaries serving in 57 countries, including 28 African nations, between 1967 and 1984 were assayed for antibodies to the human immunodeficiency virus (HIV) by enzyme-linked immunosorbent assay (ELISA) screening and Western blot confirmatory testing. Seventy sera (1.2%) from 51 missionaries (1.6%) were ELISA positive; however, on Western blot confirmatory testing none was diagnostic of HIV infection. Twenty-two (43%) of the Western blot tests were read as indeterminate, with band p17 occurring with the greatest frequency (57%), followed by p24 (23%), either alone or in combination. The significance of these equivocal results is unclear, but they do not appear to be a consequence of exposure to either HIV or the related retrovirus HTLV-I. Based on this seroprevalence survey, we conclude that missionary staff and their families were not at high risk of HIV infection between 1967 and 1984, even when serving in regions of high HIV endemicity.
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PMID:Are missionaries at risk for AIDS? Evaluation for HIV antibodies in 3,207 protestant missionaries. 277 75

We have used a recombinant vaccinia virus (VV) which expresses high levels of human immunodeficiency virus-1 (HIV-1) gag proteins to analyze the processing pathway of the gag p55 precursor. HIV-1 gag proteins were isolated from [3H]leucine-labeled VV:gag-infected H9 T lymphocytes by immunoprecipitation with either anti-p24, anti-p17, or anti-p6 antibodies. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that processing of the p55 precursor involves three major intermediates (p41a, p41b, and p39). The p41a and p39 proteins contain the p17 and p24 protein segments, and the p41b is comprised of p24 and p15 segments. On two-dimensional gels, each intermediate as well as the mature p24 and p17 proteins migrated as distinct species. [3H]Myristic acid labeling of the HIV-1 gag proteins revealed that in addition to p55 and p17, the p41a and p39 intermediates, but not p41b, are myristylated, confirming that myristylation occurs at the NH2 terminus before cleavage of the p55 precursor protein. We conclude that the myristylated HIV-1 gag p55 precursor is initially cleaved at random either at the p17/p24 junction or at two sites between p24 and p15 proteins, resulting in three intermediates (p41a, p41b, and p39) which are subsequently cleaved to yield mature gag proteins.
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PMID:Identification of protein intermediates in the processing of the p55 HIV-1 gag precursor in cells infected with recombinant vaccinia virus. 278 91

The primary interaction of HIV-1 with the target cell involves the viral large envelope protein (gp120) and the cellular CD4 molecule. mAb reacting with portions of CD4 have been shown to block HIV-1 attachment and infection. In one of the early reports describing HIV-1 cell interaction, some mAb reacting with MHC class II Ag were also found to block infection. To investigate further a possible role for MHC class II in HIV-1 binding, a cultured T lymphocyte cell line (H-9) that expresses MHC class II molecules and PHA-stimulated PBL was exposed for various time periods to concentrated viral particles and individual HIV-1 proteins. A decrease in the ability to detect the CD4a epitope and HLA-DR was observed after the cells were exposed to virus for 15, 30, and 60 min whereas HLA-DP and HLA-DQ Ag increased or remained unchanged. After 120 min of virus exposure, the CD4a epitope remained diminished whereas HLA-DR was detected at levels found on cells not exposed to virus. mAb detecting the CD4a epitope and HLA-DR, as well as alloantisera detecting the specific HLA-DR Ag on the target cell, blocked HIV-1 binding. When immunopurified gp120 was added to PHA-stimulated and unstimulated PBL, the CD4a epitope decreased in the same manner as was observed with whole virus preparations. In contrast to exposure to the intact virus, HLA-DR expression appeared to increase. Other viral proteins, p17, p24, and a portion of the small envelope protein, gp41, had no effect on the ability to detect cell surface Ag. Thus, although CD4 is the primary receptor for HIV-1 binding, HLA-DR appears to be involved in the binding site, probably by virtue of its close proximity to the CD4 molecule on the cell surface.
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PMID:HLA-DR is involved in the HIV-1 binding site on cells expressing MHC class II antigens. 235 80

An application of high resolution scanning/transmission electron microscopy (STEM) and gold-labelling techniques for the rapid detection of human immunodeficiency virus (HIV) in infected cells has been developed. Experimental in vitro studies for detecting two HIV structural proteins, gp41 and p17, were performed following an indirect labeling procedure that uses monoclonal anti-p17 and anti-gp41 antibodies as primary antibodies and 40 nm gold-linked goat antimouse IgG as secondary antibodies. The cells were then studied by STEM in the scanning mode. Unambiguous localization of the viral antigens was possible by combining the three-dimensional image provided by the secondary electron image and the atomic number-dependent backscattered electron image for the identification of the gold marker. This technique combines both the morphological information and the rapid procedures of scanning electron microscopy with the precise and sensitive antigen detection provided by the use of STEM and immunological methods. The preliminary results of its application to the study of peripheral blood mononuclear cells from four anti-HIV-seropositive patients showing the presence of specific labeling in all of them suggest that it might prove useful for early detection of HIV infection before seroconversion, as well as for quantitative studies.
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PMID:Localization of human immunodeficiency virus antigens in infected cells by scanning/transmission-immunogold techniques. 284 12

Over a period of six months, we have followed a total of six different EBV-transformed B cell lines, each of which has been infected by the human immunodeficiency virus (HIV-1). The results indicate that all of these lines were initially able to produce progeny HIV-1, but that over time three of them ceased to produce infectious virus and two lines failed to elaborate significant levels of reverse transcriptase activity into the medium. We further found that two of the latter cell lines continued to express the viral antigens p17, p24 and/or gp41, as determined by indirect immunofluorescence assay, at times after progeny HIV-1 could no longer be detected. Those cell lines which continued to secrete progeny HIV-1 did so intermittently with large amounts of virus production on some days but not others. We further found that treatment of such cells with 3' azido-3'-deoxythymidine (AZT) completely inhibited production of progeny HIV-1.
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PMID:Heterogeneity of HIV-1 replication and antigen expression in EBV-transformed B cell lines. 284


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