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

To study interactions between the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120-gp41) and the receptor in the target membrane, CD4, a new experimental system utilizing CD4-carrying plasma membrane vesicles (CD4 PMVs) was developed. CD4 PMVs were prepared by hypotonic lysis of HeLa cells expressing CD4 after infection with recombinant vaccinia virus containing the CD4 cDNA. The CD4 PMVs carried up to 680 CD4 molecules per vesicle. Their fusion with cells expressing gp120-gp41 after infection with recombinant vaccinia virus was monitored by fluorescence video microscopy by using lipophilic fluorescent dyes. Fluorescence changes as a result of fusion occurred within 30 min at 37 degrees C, and little fluorescence changes were seen with cells expressing the noncleaved HIV-1 envelope glycoprotein (gp160). The preincubation of CD4 PMVs with HIV-1 reduced its infectivity 10-fold. The CD4 PMVs were more effective in inhibiting syncytia formation than sCD4. These results demonstrate that CD4 PMVs could be used to study the mechanisms of HIV-1 envelope-mediated fusion and have the potential to inactivate HIV-1.
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PMID:Interactions of CD4+ plasma membrane vesicles with HIV-1 and HIV-1 envelope glycoprotein-expressing cells. 151 92

HIV-1-specific antibodies have been detected in the saliva of seropositive individuals and may play a role in preventing oral transmission of the virus. We have analyzed saliva samples obtained from HIV-1-seronegative individuals who were immunized with various dosages of a recombinant HIV-1 envelope glycoprotein (gp160) vaccine for the presence of antibodies to HIV-1. Antibodies specific for envelope glycoproteins were detected in saliva from all of the volunteers, with those vaccinated with the higher doses of 640 and 1,280 micrograms showing the strongest responses. Peak salivary antibody titers were obtained 4-14 weeks after vaccination; they then gradually dropped in parallel with serum antibody titers. These envelope-specific antibodies were detected in whole saliva and in submandibular saliva but not in parotid saliva, suggesting that the source of antibodies in saliva is from serum transudation. The class of reactive antibodies was found to be IgG. The HIV-1-specific antibodies in the saliva of vaccinated individuals may offer local protection against HIV-1 infection.
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PMID:Envelope-specific antibodies in the saliva of individuals vaccinated with recombinant HIV-1 gp160. 1534 43

Although hypercellularity is a common bone marrow finding in patients with human immunodeficiency virus type 1 (HIV-1) infection, the effect of HIV-1 on the hematopoietic system, which has been investigated in in vitro studies, is still controversial. In this study, we have investigated the effects of HIV-1 envelope glycoprotein, gp160, on the differentiation of hematopoietic progenitor cells derived from cord blood. Culture of cord blood mononuclear cells with gp160 resulted in enhancement of the in vitro growth of myeloid hematopoietic progenitors. To investigate the mechanism of the enhancement, adherent cells, T cells, or CD34-bearing hematopoietic progenitors were isolated and cultivated with gp160 in a variety of culture conditions. We have shown that gp160 had no direct effect on highly purified hematopoietic progenitors but exerted its enhancing effect indirectly via T cells, by induction of a humoral colony-stimulating factor(s). The activity of gp160 on T cells was abrogated by preincubation of gp160 with recombinant CD4 molecule and goat anti-gp120 antibody. These data provide evidence for a novel biological activity of HIV envelope glycoprotein, that of T-cell-mediated stimulation of myelopoiesis. Binding of gp160 with the cell surface CD4 molecule appears to be necessary for secretion of the colony-stimulating factor(s).
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PMID:Effect of human immunodeficiency virus-1 envelope glycoprotein on in vitro hematopoiesis of umbilical cord blood. 152 Aug 72

Following immunization of healthy adult volunteers with baculovirus-derived HIV-1 gp160 vaccine (rgp160), we measured lymphocyte proliferation to rgp160, the V3 loop peptide of gp160, control proteins, and phytohaemagglutinin. Four persons received injections of 40 micrograms or 80 micrograms of rgp160 vaccine at times 0, and 1, 6 and 18 months; one additional volunteer received only three injections of vaccine. Vaccination with rgp160 induced lymphocyte proliferative responses to rgp160, but not to V3 loop peptide. Repeated injection of rgp160 even at low doses induced a cellular immune response which was not attributable to T-cell recognition of the V3 loop peptide.
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PMID:Lymphocyte proliferative responses following immunization with human immunodeficiency virus recombinant GP160. The NIAID AIDS Vaccine Clinical Trials Network. 153 41

Subneutralizing concentrations of sera from human immunodeficiency virus (HIV)-1-infected patients augment HIV infection mediated by Fc receptor uptake by human monocytes and the monocytic cell line U937. Antibody-dependent enhancement (ADE) and neutralization activity were studied in the sera of HIV-1 antibody-negative volunteers who had been immunized with three 40-micrograms doses of a recombinant gp160 (rgp160) candidate HIV vaccine. Volunteers were vaccinated with rgp160 or a hepatitis B vaccine as a control on days 0, 30, and 180. Sera were obtained before and after three doses of vaccine and were tested for ADE and neutralization activity. Serum samples collected before vaccination showed neither neutralization nor ADE activity. Thirteen sera from volunteers who received gp160 and four from placebo recipients failed to show ADE. Three sera showed low levels of neutralization of strain IIIB of HIV. Vaccination with this dose of rgp160 produced neutralizing antibodies in some subjects but did not induce detectable enhancing antibodies.
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PMID:Studies of antibody-dependent enhancement of human immunodeficiency virus (HIV) type 1 infection mediated by Fc receptors using sera from recipients of a recombinant gp160 experimental HIV-1 vaccine. 153 59

The cell surface glycoprotein, CD4, is the receptor for human immunodeficiency virus (HIV) in T lymphocytes. Following HIV infection, there is reduced expression of CD4 on the cell surface, and this downregulation probably results, at least in part, from the formation of complexes containing the HIV type 1 (HIV-1) glycoprotein precursor (gp160) and CD4 that are not transported from the endoplasmic reticulum (ER). At the plasma membrane of T cells, CD4 is tightly associated with a cytoplasmic tyrosine kinase (p56lck) that is involved in T-cell activation. Using a transient expression system with HeLa cells, we show by pulse-labeling and immunoprecipitation that newly synthesized CD4 can associate with p56lck before CD4 is transported from the ER. In the presence of HIV-1 gp160, a ternary complex of gp160-CD4 and p56lck forms in the ER. Using confocal immunofluorescence microscopy, we observed complete retention of p56lck in the ER. Such mislocation of a tyrosine kinase to the cytoplasmic face of the ER could play a role in lymphocyte killing caused by HIV infection or expression of gp160 alone.
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PMID:Human immunodeficiency virus type 1 glycoprotein precursor retains a CD4-p56lck complex in the endoplasmic reticulum. 154 63

The gp160 of HIV-2 was studied with the aid of computer programs that provide the hydrophilicity, surface probability, flexibility, and antigenicity index of the amino-acid sequence in a polypeptide chain. Such analyses allow the identification of hydrophobic amino-acid domains in the polypeptide chain that may serve as putative proteolytic cleavage signals and putative antigenic domains. It was possible to define the function of hydrophobic domains in the polypeptide chain that serve as signals and amino-acid sequences involved in the transfer of the polypeptide through the cellular membrane by the cellular signal recognition protein (SRP) complex. By comparison to reported properties of HIV-1 gp160 and SIVMAC gp160, it was possible to define antigenic domains in the loops of gp120 resulting from the reported interchain disulfide bonds defining putative antigenic domains specific for HIV-2.
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PMID:Computer predictions of functional, topogenic, and antigenic domains in human immunodeficiency virus-2 envelope glycoprotein. 154 12

The human and simian immunodeficiency virus envelope glycoproteins, which mediate virus-induced cell fusion, contain two putative amphipathic helical segments with large helical hydrophobic moments near their carboxyl-terminal ends. In an attempt to elucidate the biological role of these amphipathic helical segments, we have synthesized peptides corresponding to residues 768-788 and 826-854 of HIV-1/WMJ-22 gp160. Circular dichroism studies of the peptides showed that the alpha helicity of the peptides increased with the addition of dimyristoyl phosphatidylcholine (DMPC) indicating that the peptides form lipid-associating amphipathic helixes. The peptides solubilized turbid suspensions of DMPC vesicles, and electron microscopy of peptide-DMPC mixtures revealed the formation of discoidal complexes, suggesting that the peptides bind to and perturb lipid bilayers. The peptides were found to lyse lipid vesicles and caused carboxyfluorescein leakage from dye-entrapped egg phosphatidylcholine liposomes. The peptides also lysed human erythrocytes and were found to be toxic to cell cultures. At subtoxic concentrations, the peptides effectively inhibited the fusion of CD4+ cells infected with recombinant vaccinia virus expressing human immunodeficiency virus (HIV)-1 envelope proteins. Based on these results, and reported studies on the mutational analysis of HIV envelope proteins, we suggest that the amphipathic helical segments near the carboxyl terminus of HIV envelope proteins may play a role in lysis of HIV-infected cells and also may modulate the extent of cell fusion observed during HIV infection of CD4+ cells.
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PMID:Membrane interactions of synthetic peptides corresponding to amphipathic helical segments of the human immunodeficiency virus type-1 envelope glycoprotein. 155 18

The European collaborative study of HIV-infected pregnant women in Europe now indicates a 13% risk of fetal HIV infection (originally thought to be about 30%, and possibly higher in some countries). Several reports suggest trans-placental passage. However, the detailed mechanisms associated with such vertical transmission have not yet been clarified. We have examined the possibility that HIV enters placental tissue from maternal blood via binding to CD4 and Fc receptors (FcR) at the trophoblast level, allowing intraplacental infection. Here we report the detection of several FcR with distinct localization in the placental villus as well as CD4 surface expression on human trophoblast cells. In addition, we show that trophoblastic cells interact specifically with the gp120/gp160 viral envelope protein. By their tissue localization, these receptors could be responsible for the entry of HIV into the fetal placental cells. Furthermore, purified placental cells can be directly infected by HIV in vitro, and the infection is inhibited by soluble CD4. This suggests a crucial role of the CD4 receptor but an additional way of entry cannot be excluded. Such an in vitro model may be suitable for further studies concerning placental HIV transmission and its prevention.
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PMID:Human trophoblast cells express CD4 and are permissive for productive infection with HIV-1. 156 94

The first trial of an anti-HIV immunization, using a recombinant vaccinia virus expressing gp160 (rV) for priming and paraformaldehyde-fixed rV-infected PBLs and soluble gp 160 for boosting, clearly showed an in vitro HIV-protective immune reaction. This result led us to carry out an additional 2 year Phase I clinical trial in 25 HIV-seronegative volunteers, using HIV gp 160 antigens for immunization in four different protocols. The 2 year trial showed (a) the safety of the preparations, (b) a transient humoral immunity following each boost, and (c) a long-lasting memory T-cell response. Memory cytotoxic T-lymphocytes (CTLs) induced by gp 160 antigen with or without vaccinia vector lysed HLA class I restricted target cells expressing HIV-1 env antigens. These results are consistent with CTLs being an effective component of an AIDS vaccine to control cell-to-cell viral replication, dissemination in the organism, and subsequent evolution toward AIDS.
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PMID:A 2-year follow-up of an anti-HIV immune reaction in HIV-1 gp160-immunized healthy seronegative humans: evidence for persistent cell-mediated immunity. 158 88


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