Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A family of oligonucleotides and phosphorothioate oligonucleotide analogues was synthesized with a cholesteryl group tethered at the 3'-terminal internucleoside link. This modification, introduced to enhance interaction of the polyanions with cell membranes, significantly increases the antiviral activity of the oligomers, as judged by inhibition of syncytia formation and expression of viral proteins p17, p24, and reverse transcriptase for human immunodeficiency virus 1 in Molt-3 cells. In the most favorable case, with a 20-mer cholesteryl-phosphorothioate derivative, complete inhibition by all assays was obtained with an oligomer concentration of 0.2 microM. Even decamers were active, and some antiviral activity was observed for a heptanucleotide cholesteryl-phosphorothioate derivative, which binds very poorly to complementary oligonucleotides. These facts, and the finding that the activity of the phosphorothioate decamers does not correlate with a specific sequence, suggests that a mechanism other than "antisense inhibition" may be operative in these systems.
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PMID:Cholesteryl-conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture. 277 42

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

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

The prevalence of antibodies to human immunodeficiency virus (HIV = LAV/HTLV-III) in a rural population from the Ifakara area in southeastern Tanzania was investigated. Sera from 286 individuals collected from 1982 to 1984 in connection with a study on liver disorders were tested by an ELISA. Fifty-two (18.2%) of the sera were found positive. While the positives were largely confirmed by one commercial ELISA, they were completely negative by two others. Confirmatory testing by Western blot and competition Western blot showed that the reactivity detected by more sensitive of these assays was largely due to IgG antibodies binding to the HIV core (gag) proteins p17, its precursor p55 and, in some cases, p24. These tests also indicated, however, that the reactive antibodies could not have been elicited by HIV, but possibly by an unknown retrovirus or another cross-reactive agent. Thus, by 1984, the area investigated was largely free of HIV infection, but a significant proportion of its population may harbor another retrovirus of unknown pathogenicity.
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PMID:Specificity of human immunodeficiency virus (LAV/HTLV-III)-reactive antibodies in African sera from southeastern Tanzania. 287 46

In a longitudinal study, human immunodeficiency virus type 1 (HIV-1) antigen (HIV-Ag) was measured in serum specimens from 54 children with HIV-1 infection followed for a median duration of 17 months. The persistent detection of free HIV-Ag in a group of 25 children was associated with clinical deterioration in 22 (88%) and a mortality of 52%, whereas the persistent nondetection of free HIV-Ag in a group of 18 children was associated with clinical deterioration in five (28%) and a mortality of 11% during the period of observation. Nine children had transient HIV-1 antigenemia and two children converted from HIV-Ag negative to positive during the study. Free HIV-Ag levels varied inversely with antibody reactivity to viral core proteins p24 and p17 determined by Western immunoblot, suggesting either the formation of immune complexes or a balance between viral expression and the host immune response. Five mother-infant pairs were studied for HIV-Ag expression in the perinatal period. In three of these pairs, both mother and infant were HIV-Ag negative, in one pair the mother had high levels of HIV-Ag and the infant was HIV-Ag negative. In the remaining mother-infant pair, the neonate became HIV-Ag positive but the mother was HIV-Ag negative prepartum and postpartum. These data suggest that HIV-Ag probably does not cross the placenta and that the detection of free HIV-Ag in the offspring of a HIV-1 infected mother most likely indicates viral infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Persistent human immunodeficiency virus type 1 antigenemia in children correlates with disease progression. 290 81

The effect of cyclosporine A (CyA) on the ability of the human immunodeficiency virus type 1 (HIV-1) to infect the H-9 T-cell leukemic line, as well as interleukin-2 (IL-2)-grown human peripheral blood-derived lymphocytes, has been studied. Pretreatment of H-9 cells and human lymphocytes with CyA over 24 hours completely prevented viral infection over a 21-day period, whereas the addition of drug at two hours postinfection with HIV-1 had a significant inhibitory effect on viral replication and expression of the virus-specific antigens p17 and p24. However, if CyA was added at later times to these lymphocytic cells, this inhibitory effect was lost. Indeed, the removal of CyA from cultures that had been treated from two hours after infection led to the rapid production of progeny virus. HIV-1 was able to infect peripheral blood lymphocytes obtained from each of four kidney allograft recipients on long-term CyA antirejection therapy, as long as drug was not included in the culture medium. In addition, we asked what effect pretreatment with CyA of cells of the U-937 monocytic line and primary cultures of human monocytes/macrophages might have on infection by HIV-1. CyA had no demonstrable effect on the ability of HIV-1 to infect cells of either type.
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PMID:The effect of cyclosporine A on infection of susceptible cells by human immunodeficiency virus type 1. 290 90


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