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

The envelope (membrane) glycoprotein of HIV is essential for virus attachment and entry into host cells. Additionally, when expressed on the plasma membrane of infected cells, the envelope protein is responsible for mediating cell-cell fusion which leads to the formation of multinucleated giant cells, one of the major cytopathic effects of HIV infections. The envelope glycoproteins of HIV contain regions that can fold into amphipathic alpha-helixes, and these regions have been suggested to play a role in subunit associations and in virus-induced cell fusion and cytopathic effects of HIV. We therefore tested the possibility that amphipathic helix-containing peptides and proteins may interfere with the HIV amphipathic peptides and inhibit those steps of HIV infection involving membrane fusion. Apolipoprotein A-I, the major protein component of high density lipoprotein, and its amphipathic peptide analogue were found to inhibit cell fusion, both in HIV-1-infected T cells and in recombinant vaccinia-virus-infected CD4+ HeLa cells expressing HIV envelope protein on their surfaces. The amphipathic peptides inhibited the infectivity of HIV-1. The inhibitory effects were manifest when the virus, but not cells, was pretreated with the peptides. Also, a reduction in HIV-induced cell killing was observed when virus-infected cell cultures were maintained in presence of amphipathic peptides. These results have potential implications for HIV biology and therapy.
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PMID:Apolipoprotein A-I and its amphipathic helix peptide analogues inhibit human immunodeficiency virus-induced syncytium formation. 217 Apr 46

Immunization of two macaque monkeys with recombinant vaccinia viruses encoding the env gene of HIV-1 (VV-gp160) resulted in demonstrable levels of gp160, gp120 and gp41-specific immunoglobulins in both animals. The virus used to immunize one of the monkeys additionally expressed the human IL-2 gene, which encoded human IL-2 (VV-gp160-IL-2). No toxic side-effects of vaccine-delivered IL-2 were observed. Despite marked attenuation of virulence by the coexpressed lymphokine, the levels of vector-specific antibodies in both animals were similar. Some differences in the HIV-specific reactivity patterns were detected. Serum reactivity of monkey #A56 (VV-gp160) was directed against gp41, whereas monkey #B58 (VV-gp160-IL-2) showed a wider range of recognition, with higher antibody titres against the HIV lysate preparation. Furthermore, this study demonstrates the capacity to boost antibody responses to the vector and coexpressed HIV antigens in primates which are already immune.
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PMID:Response of monkeys to vaccination with recombinant vaccinia virus which coexpress HIV gp160 and human interleukin-2. 220 Jul 48

In the previous AIDS symposium organized by the Society, Witte and Witte (1) made a number of predictions, one of which was that in AIDS patients, "Lymph from the thoracic duct should be strongly positive for HIV." Though direct evidence for this is lacking, some early experiments of ours with vaccinia virus (2) are fully in accord with this prediction, to which they lend indirect support. In rabbits, nasally instilled vaccinia virus spreads via the lymphatic pathway (afferent peripheral lymph--deep cervical gland--efferent lymph--thoracic duct) in as short a time as nine hours. Virus is transported mainly in cells, for when the efferent lymph is centrifuged virus is found only in the cell sediment. It seems reasonable to assume that other viruses, including HIV, are similarly disseminated. Paradoxically, the lymphomyeloid complex both greatly facilitates the spread of virus, and at the same time, mounts the immunological defenses against the virus which it so effectively helps to disseminate. Whatever the portal of entry of the virus, its transport by migrating cells ensures its dissemination throughout the lymphomyeloid complex, including the bone marrow. The bone marrow is an integral part of the complex, as the prime source of B lymphocytes, T lymphocyte precursors, and many of the antigen-presenting cells as well as the granulocytes. There is some evidence concerning possible ways in which the bone marrow can contribute to the development of immune deficiency in AIDS patients. The bone marrow merits further study in this context.
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PMID:Virus dissemination via the lymphomyeloid complex. 221 64

Recombinant vaccinia viruses that contained regions of the gag-pol open reading frames of human immunodeficiency virus type 1 (HIV-1) were constructed. Cells infected with recombinants containing both gag and protease genes expressed and processed HIV gag antigens efficiently. Processing was much reduced in cells infected with recombinants containing only gag, but not the protease gene. However, significant amounts of p41 were produced by protease-defective recombinants. This protein was immunoreactive with p24-specific monoclonal antibodies and was produced in a truncated form by a recombinant containing a 3' deletion in the p15 coding region of gag ORF. These results indicate that p41 could represent an alternative gag precursor with N-terminal sequences derived from p24 and C-terminal from p15. Ultrastructural analysis of recombinant-infected cells revealed that the gag antigens expressed were assembled into retrovirus-like particles and were secreted into culture medium. This assembly process was not dependent on HIV protease function, because immature core particles were produced by recombinants lacking HIV-1 protease functions. Immunization of mice and chimpanzees with vaccinia-HIVgag recombinant viruses generated both antibody and cell-mediated immune responses to HIV gag antigens. These recombinants are therefore useful not only for studying HIV virion processing and assembly, but also for designing immunogens for the prophylaxis and immunotherapy against AIDS.
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PMID:Processing, assembly, and immunogenicity of human immunodeficiency virus core antigens expressed by recombinant vaccinia virus. 221 27

Previous studies had tested the susceptibility of two macaque species, Macaca nemestrina and M. mulatta, to infection with the primate lymphotropic lentivirus SIVmne. In this report we describe the results obtained after infecting eleven M. fascicularis with SIVmne. Six of the animals had previously been immunized with a recombinant vaccinia virus expressing the envelope gene of HIV-1. All eleven animals became seropositive. To date ten animals have died 43 to 155 weeks post infection of an AIDS-like disease.
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PMID:Inoculation of Macaca fascicularis with simian immunodeficiency virus, SIVmne immunologic, serologic, and pathologic changes. 223 89

The envelope (env) glycoproteins of human immunodeficiency viruses type 1 (HIV-1) and type 2 (HIV-2) form dimers shortly after synthesis. Analysis of the simian immunodeficiency virus (SIV) env protein expressed by a recombinant vaccinia virus revealed that it, too, forms stable homodimers. When the HIV-1 and SIV env proteins or the HIV-1 and HIV-2 env proteins were coexpressed in the same cells, heterodimers were formed. Thus, the env proteins of HIV-1, HIV-2, and SIV possess a functionally conserved domain involved in subunit-subunit recognition and assembly that likely involves the ectodomain of gp41.
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PMID:Human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus env proteins possess a functionally conserved assembly domain. 235 32

A recent isolate of human immunodeficiency virus type 2 (HIV-2) designated HIV-2ST is deficient in its ability to cause the typical cytopathic effects of HIV infection. The pathogenic potential of HIV-2 in inducing human disease may be less than that of HIV-1, and it is of particular interest to establish the basis for the reduced cytopathogenicity of this isolate in vitro. Utilizing recombinant vaccinia viruses (rVV) carrying the envelope genes (env) of HIV-2ST or those of fully cytopathic HIV-1 or HIV-2 isolates, we have investigated envelope glycoprotein expression, processing, transport, and biological function. Radioimmunoprecipitation and polyacrylamide gel electrophoresis (RIP-PAGE) of rVV-infected cell lysates indicated that the proteins expressed by each recombinant were synthesized, processed, and recognized by specific antisera. Immunofluorescence studies showed that the recombinant env gene products of HIV-2ST and HIV-2ROD reach the cell surface and are retained there in similar amounts. Whereas cells expressing the HIV-1 or HIV-2ROD env gene products were found to undergo fusion with uninfected CD4+ cells, no syncytium formation was observed with three CD4+ cell lines exposed to the cells expressing the envelope glycoproteins of HIV-2ST on their surfaces; one CD4+ lymphoid cell line (SupT1) exhibited few very small syncytia in the presence of recombinant HIV-2ST envelope glycoproteins. The failure of the HIV-2ST envelope glycoprotein to induce cell fusion was not the result of an inhibition by cell-associated CD4, since fusion was also not observed when rVVST-infected CD4- cells were cocultured with CD4+ cells. Thus, the HIV-2ST envelope protein itself is defective in its ability to induce cell fusion. Furthermore, the expression, processing, transport, and surface stability of env products of HIV-2ST are unlikely to be responsible for its attenuation, suggesting that the molecular interactions between its env products and target cell membranes are significantly altered.
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PMID:The env protein of an infectious noncytopathic HIV-2 is deficient in syncytium formation. 236 16

A synthetic peptidemimetic substrate of the human immunodeficiency virus 1 (HIV-1) protease with a nonhydrolyzable pseudodipeptidyl insert at the protease cleavage site was prepared. The peptide U-81749 inhibited recombinant HIV-1 protease in vitro (inhibition constant Ki of 70 nanomolar) and HIV-1 replication in human peripheral blood lymphocytes (inhibitory concentration IC50 of 0.1 to 1 micromolar). Moreover, 10 micromolar concentrations of U-81749 significantly inhibited proteolysis of the HIV-1 gag polyprotein (p55) to the mature viral structural proteins p24 and p17 in cells infected with a recombinant vaccinia virus expressing the HIV-1 gag-pol genes. The HIV-1 like particles released from inhibitor-treated cells contained almost exclusively p55 and other gag precursors, but not p24. Incubation of HIV-like particles recovered from drug-treated cultures in drug-free medium indicated that inhibition of p55 proteolysis was at least partially reversible, suggesting that U-81749 was present within the particles.
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PMID:A synthetic HIV-1 protease inhibitor with antiviral activity arrests HIV-like particle maturation. 240 86

A human monoclonal antibody (IgG2, lambda), 1B8.env, was produced, reactive with the envelope glycoprotein of human immunodeficiency virus (HIV). The antibody specifically stains cells infected with HIV, as assessed by indirect immunofluorescence analysis and reacts with determinants displayed on the surface of infected cells. In Western blot analysis, the antibody reacts with bands of 160 and 41 kD, consistent with the precursor and transmembrane forms of the HIV envelope glycoprotein. The antibody also reacts specifically in immunofluorescence and Western blot analysis with cells infected with the recombinant vaccinia virus VSC-25, which contains the envelope gene of HIV. With the lambda gt11 expression vector, the epitope recognized by 1B8.env was mapped to a region of 11 amino acids in the coding region of gp41. This domain is highly conserved between several otherwise highly variable HIV isolates. In addition, this epitope appears to be recognized by the vast majority of HIV seropositive individuals. Although antibody IB8.env does not neutralize HIV virion infectivity or virally mediated cell fusion, the results presented here demonstrate the feasibility of generating and characterizing human monoclonal antibodies to HIV with these techniques. Additional antibodies produced in this manner will help to further characterize the humoral response to HIV infection, define biologically significant determinants on HIV proteins, and may be useful in clinical applications.
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PMID:Characterization and epitope mapping of a human monoclonal antibody reactive with the envelope glycoprotein of human immunodeficiency virus. 244 58

Characterization of the host immune response to human immunodeficiency virus type 1 (HIV-1) is critical to the rational design of an effective AIDS vaccine. In this study, cytotoxic T lymphocytes (CTL) specific for HIV-1 reverse transcriptase (RNA-dependent DNA polymerase) were found in blood samples from HIV-1-infected individuals. CTL targets were prepared by immortalizing B cells from ten seropositive and six seronegative individuals, and then infecting these cells with recombinant vaccinia viruses containing HIV-1 genes. CTL directed against autologous B lymphoblasts expressing HIV-1 reverse transcriptase were detected in fresh blood samples from eight HIV-1 seropositive subjects, but in no seronegative controls. The effector cells were identified as major histocompatibility complex-restricted CD3+CD8+ lymphocytes. Because the HIV-1 pol gene is highly conserved among different isolates and generates both humoral and cellular immune responses, it bears consideration for inclusion in a candidate AIDS vaccine.
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PMID:HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals. 245 Dec 88


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