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

Most attempts to produce a vaccine against HIV-1 infection are utilizing envelope protein components. Hypothetically such vaccine candidates could stimulate production of antibodies that enhance HIV-1 infection via the macrophage route of entry and, consequently, cannot be detected in the conventional neutralization assay. To study this hypothesis we report an assay designed to evaluate the protective/enhancing activity of serum from seropositive immunized or infected individuals. Highly purified activated FcR-bearing monocytes-macrophages were infected with HIV-1 in the presence of the sera, then washed and cocultured with activated peripheral blood mononuclear cells (PBMC) from a normal donor. Productive viral infection, as evaluated by p24 antigen semiquantitative assay in the culture supernatants, allow evaluation of protective/enhancing activity of the sera. The data clearly show that protective rather than enhancing activity is present in the serum of env protein-immunized individuals.
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PMID:Discriminating between protective and enhancing HIV antibodies. 210 24

The envelope (env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) consists of two noncovalently associated subunits, gp120 and gp41, that are formed gradient sedimentation, polyacrylamide gel electrophoresis, gradient sedimentation, polyacrylamide gel electrophoresis, and chemical cross-linking, we show that gp160 is synthesized as a monomer and subsequently forms stable homodimers. The molecule remains dimeric after cleavage to gp120/gp41 but is less stable to detergent solubilization and centrifugation. Analysis of wild-type and mutated env proteins indicated that interactions between the ectodomain regions of adjoining gp41 subunits are important for dimer formation and stability. A higher-order oligomeric form was also recovered, probably a tetramer consisting of two noncovalently associated dimers. The proposed subunit composition of the HIV-1 env protein is identical to that previously observed for the paramyxovirus envelope proteins F and HN.
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PMID:Oligomeric structure of the human immunodeficiency virus type 1 envelope glycoprotein. 230 May 52

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

We have shown that 6D5 cells infected with the HIV-1 strain HTLV-III451 (6D5(451)) secreted viral envelope proteins gp160 and gp120 into the culture medium. Single cell cloning of 6D5(451) cells separated three distinct phenotypes. All clones secreted unprocessed env protein gp160 along with gp120. Only one phenotype produced infectious virus and contained normally processed gag proteins. The second phenotype was associated with nonproducer cells expressing only the env gene but no extracellular particles. The third phenotype synthesized Pr53gag but no reverse transcriptase, nor did it process the gag precursor. Only immature particles could be seen in the culture. Cells of the first and the third phenotypes produced two sizes of gp160, the normal and one with a small truncation at the C-terminus. Phenotype 2 only produced the smaller gp160. In all cases the gp160 that was secreted into the medium was the truncated molecule.
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PMID:Differential viral gene expression and its effect on the biological properties of the cell clones of an HIV-1-infected cell line. 235 62

In previous studies, we have used antisera raised to envelope (env)-gene-encoded synthetic peptides to identify a region of (HIV) glycoprotein (gp) 120 env protein designated SP10 that contains a type-specific neutralizing determinant. To develop a polyvalent, synthetic peptide inoculum that can evoke both neutralizing antibodies and T cell proliferative responses to more than one HIV isolate, synthetic peptides containing type-specific neutralizing determinants of gp120 from HIV isolates HTLV-IIIB (IIIB), HTLV-IIIMN (MN) and HTLV-IIIRF (RF) were coupled to a 16 amino acid T cell epitope (T1) of HIV-IIIB gp120 and used to immunize goats. Goat antisera to each T1-SP10 peptide derived from the SP10 region of gp120 of IIIB, MN, and RF neutralized HIV isolates IIIB, MN and RF in a type-specific manner. Moreover, peripheral blood T cells from immunized goats also proliferated in a type-specific manner to peptides derived from gp120 of IIIB, MN, and RF. When combined in a trivalent inoculum, T1-SP10 peptides from HIV-1 isolates IIIB, MN, and RF evoked a high titered neutralizing antibody response to isolates IIIB, MN, and RF in goats and as well induced immune T cells to undergo blast transformation in the presence of peptides derived from gp120 of all three HIV isolates. The T1 portion of the T1-SP10 construct was shown to induce a B cell antibody response against determinants within the T1 peptide in addition to inducing T cell proliferative responses in immune goat T cells. Moreover, the SP10 portion of the T1-SP10 constructs not only induced B cell antibody production but also induced type-specific T cell proliferative responses localized to the C-terminal variable sequences of the SP10 peptides. Finally, the T1-SP10 peptide construct induced memory T cell proliferative responses to native gp120 env protein. Thus, combinations of homologous SP10 region synthetic peptides containing type-specific neutralizing determinants and T cell epitopes of HIV gp120 may be useful in man to elicit high titered neutralizing B cell responses and, as well, T cell responses to more than one HIV isolate.
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PMID:Polyvalent human immunodeficiency virus synthetic immunogen comprised of envelope gp120 T helper cell sites and B cell neutralization epitopes. 246 21

Three IgM monoclonal antibodies raised against synthetic peptide analogs of a hydrophilic region of the gp41 transmembrane env protein of HIV-1 neutralize different HIV-1 isolates but not HIV-2 isolates, as determined by HIV titration and by syncytial inhibition assays. VSV (HIV-1) pseudotypes, however, were not neutralized, indicating that gp41 was not accessible to these antibodies on the pseudotype particles. The antibodies affect early steps in adsorption and penetration of HIV-1.
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PMID:Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide. 283 59

The first experimental immunization of humans against the AIDS retrovirus, HIV-1, was started in a series of HIV seronegative, healthy volunteers in November 1986. For the primary vaccination recombinant vaccinia virus (V25) expressing the complete gp160 env protein of the HTLV-IIIB strain of HIV-1 was introduced by scarification. This elicited a weak primary response which we subsequently attempted to enhance by additional immunizations (boosting), using four different immunization protocols. We report here that intravenous injection of paraformaldehyde-fixed autologous cells infected in vitro with V25 (individual D.Z.) gave the best results. This individual received second and third boosts of intramuscular gp160 derived from an HTLV-IIIB clone using the hybrid vaccinia virus/bacteriophage T7 expression system. An anamnestic humoral and cellular immune reaction was achieved for over one year after the original vaccination, with high levels of antibodies to the viral envelope, and neutralizing antibodies against divergent HIV-1 strains such as HTLV-IIIB and HTLV-IIIRF (also called HTLV-III HAT) after the first boost. In addition, group-specific cell-mediated immunity and cell-mediated cytotoxicity against infected T4 cells were obtained after the primary vaccine and enhanced by the boosts. Finally, skin tests showed both immediate and delayed hypersensitivity to gp160 in vivo. Although this protocol is not practical for a large scale vaccine trial, our results show for the first time that an immune state against HIV can be obtained in man.
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PMID:A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS. 316 62

The 1st experimental immunization of humans against the AIDS retrovirus HIV-1 was begun in November 1986 among a group of HIV-seronegative healthy volunteers. A priming, involving a vaccine virus recombinant (V25) expressing Gp 160 env determinants of HTLV-III B at the surface of the infected cells was utilized. This priming, which induced a weak immune reaction, was performed on HIV-seronegative French and Zairian individuals living in Kinshasa, Zaire. These results prompted a boost to the primary immune response. 4 different protocols were used: the slow drip intravenous infusion with paraformaldehyde-fixed autologous cells infected with V25; repeated scarification with V25 for the 2nd protocol; scarifications with fragments of Gp 120 env protein; and intramuscular injections of purified autologous cell membrane infected with V25. The results of the immune reaction obtained after these boosts indicated the following: The last 3 protocols showed a cell- mediated immunity (CMI) that did not significantly enhance in comparison with CMI obtained after V25 priming alone. Moreover, the sera showed low and variable neutralizing antibody titers 1-4 months after boosting. By contrast, boosting with V25 infected fixed cells (D.Z.) provided strong humoral and cellular group specific anamnestic immune responses. Indeed, high levels of antibodies to viral envelope and neutralizing antibodies against divergent HIV-1 strains were observed. Group- specific CMI and cell mediated cytotoxicity were enhanced by boosts. Skin tests showed high mediated and delayed hypersensitivity to Gp 160 in vivo. For the 1st time, these results show that an immune state against HIV can be obtained in a man. (author's modified)
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PMID:[Immunization against the human immunodeficiency virus in Zaire]. 322 92

The lysis of virally infected cells by CTLs requires the recognition of processed fragments of viral proteins presented in association with class I MHC molecules on the surfaces of infected cells. Processing begins in the cytosol with the degradation of viral proteins into peptides that are then transported into the endoplasmic reticulum (ER) for association with newly synthesized class I molecules. Transport is mediated by a heterodimer of the MHC-encoded proteins, transporter associated with Ag presentation (TAP)-1 and TAP-2. Uncertainty exists over the site of processing of viral envelope (env) proteins. The extracellular domains of env proteins are not present in the cytosol, the site in which the class I-restricted Ag-processing pathway begins. Rather, the ecto-domains of env proteins are cotranslationally translocated into the ER during biosynthesis. We have analyzed the processing of the HIV-1 env protein by using a large series of env-specific human CD8+ CTL clones. These studies have led to the delineation of two distinct processing pathways. The first pathway permits a subset of class I-restricted epitopes in the ecto-domain of the env protein to be generated efficiently by a TAP-1/2-independent mechanism localized to the ER or a premedial Golgi compartment. A second, more general pathway that is capable of generating all env epitopes uses as a substrate env protein mislocalized to the cytosol and produces peptides that are transported from the cytoplasm to the ER in a TAP-1/2-dependent fashion.
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PMID:An epitope-selective, transporter associated with antigen presentation (TAP)-1/2-independent pathway and a more general TAP-1/2-dependent antigen-processing pathway allow recognition of the HIV-1 envelope glycoprotein by CD8+ CTL. 753 43

We have previously identified a VEINCTR peptide common to both the Fasmolecule and HIV-1 gp120. Here we report the characterization in PBMCs from HIV-1-infected individuals of a CD8+ class I restricted CTL activity directed towards this peptide. The peptide is highly conserved in various HIV-1 strains, being located at amino acid 287-293 (VEINCTR), within an epitope known as cell T epitope on the env protein of human immunodeficiency virus type-1. Cell cultures were obtained by polyclonal activation using autologous blast cells and CTL lines generated from frozen peripheral blood lymphocytes of HIV-1 seropositive donors by stimulation with the peptide and recombinant interleukin-2. The env-specific CTL turned out to kill autologous target cells infected with a recombinant vaccinia virus containing the env gene of HIV-1 or pulsed with peptide. Specificity was determined using shorter peptides. The CTL activity was directed against autologous target cells presenting the heptapeptide which is site located in the Fas molecule, known to be functionally involved in T-cell apoptosis.
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PMID:Cytotoxic T lymphocytes specific for the synthetic VEINCTR peptide, a sequence found within the Fas molecule and env gp120 in the blood of HIV-1 seropositive individuals. 758 Aug 39


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