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

Five in-frame stop mutations in the HIV-1 env gene, which lead to the production of env gene products truncated within the cytoplasmic C-terminal tail, have been generated and their effects on membrane fusion capacity, glycoprotein incorporation into virus particles, infectivity, and cytopathogenicity were analyzed. The resulting truncated glycoproteins were processed normally, were transported to the cell surface, and were able to induce CD4-dependent membrane fusion. The membrane fusion capacity of one of the mutant glycoproteins with a truncation of 144 amino acids was increased to about double of that induced by wild-type glycoprotein. With a single exception, the truncated viral glycoproteins were incorporated into virus particles which were infectious and cytopathic for permissive MT-4 cells. The infection kinetics with the mutated viruses were, however, delayed to varying degrees in comparison to infection with wild-type virus. Nevertheless, in each case, PCR amplification and direct sequencing of viral DNA in the infected cultures confirmed the presence of the mutant and the absence of revertant DNA. The mutant virus encoding a viral glycoprotein with the longest truncation (144 amino acids), in which only 7 cytoplasmic C-terminal amino acids in gp41 remain, resulted in infection kinetics in MT-4 cells which were only marginally delayed in comparison to those induced by wild-type virus. This means that these C-terminal 144 amino acids of gp41 are not necessary for glycoprotein incorporation into virus particles nor do they significantly contribute to the infectivity nor the cytopathogenicity of HIV-1 in MT-4 cells.
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PMID:Retained in vitro infectivity and cytopathogenicity of HIV-1 despite truncation of the C-terminal tail of the env gene product. 160 8

The lectin-like protein analogous to bovine conglutinin was purified from human serum. The carbohydrate-binding ability of conglutinin-like protein was inhibited by D-mannose, N-acetylglucosamine and L-fucose as well as by mannan-containing oligosaccharides. By applying a lectin-based ELISA system it was demonstrated that conglutinin-like protein binds to human immunodeficiency virus-1 (HIV-1) glycoprotein 120 (gp120) via its carbohydrate binding site. In vitro experiments with T-lymphoblastoid CEM cells revealed that conglutinin-like protein abolishes infection by HIV-1; a 50% cytoprotective concentration of 23.9 micrograms/ml was measured. These findings demonstrate that human conglutinin-like protein binds to HIV-gp120 and inhibits, under the described in vitro conditions, CEM cell infection.
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PMID:Inhibition of human immunodeficiency virus-1 infection by human conglutinin-like protein: in vitro studies. 161 96

The effect of alkaline pH and alkaline hydrolysis on the physico-chemical and biological properties of endotoxin (ET) isolated from Serratia marcescens ATCC 13477 by the Biovin procedure was studied. Major emphasis was put on the ion exchange column chromatography and immune adjuvant activity (ADA) of the alkali treated samples. To measure changes in some endotoxicity parameters, Limulus lysate clotting (LAL), chick embryo lethality, Shwartzman skin reactivity and in vitro TNF release were measured. The toxic properties of ET, with the unique exception of the Shwartzman skin reactivity, rapidly diminished during alkaline treatment. As immunogen CBre3, a recombinant HIV glycoprotein which spans the C terminus of gp 120 and the N terminus of gp 41, was used in CD-1 mice, alkali treated and immediately neutralized ET samples (zero time) were inactive as adjuvants, in some cases immunosuppression could be clearly seen. But if the alkaline hydrolysis was continued for 6 h, the ADA became higher than it had been for the starting ET sample. Further alkaline hydrolysis eliminated the ADA of the samples. Both NaOH and propylamine acted similarly on the ET preparation. Reaction kinetic studies of the NaOH detoxification indicated the cleavage of ester bound acyl groups with low binding energy. Chemical analyses of the samples revealed that changes occurred in the fatty acid composition, characterized by a loss of approximately half of the 3-OH myristic acid content.
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PMID:Molecular requirements of endotoxin (ET) actions: changes in the immune adjuvant, TNF liberating and toxic properties of endotoxin during alkaline hydrolysis. 162 14

A simple, reliable ELISA for the quantitative detection of the envelope glycoproteins of both HIV and SIV is described. It incorporates the snowdrop lectin GNA to capture the glycoprotein antigens and combines the high selectivity of GNA binding with its broad reactivity with the glycoproteins of HIV-1, HIV-2 and SIV.
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PMID:An ELISA utilizing immobilised snowdrop lectin GNA for the detection of envelope glycoproteins of HIV and SIV. 162 22

Many retroviruses, including the human and simian immunodeficiency viruses, contain a leucine zipper-like repeat in a highly conserved region of the external domain of the transmembrane (TM) glycoprotein. This region has been postulated to play a role in stabilizing the oligomeric form of these molecules. To determine what role this region might play in envelope structure and function, several mutations were engineered into the middle isoleucine of the leucine zipper-like repeat of the human immunodeficiency virus type 1 (HIV-1) TM protein. A phenotypic analysis of these mutants demonstrated that conservative mutations (Ile to Val or Leu) did not block the ability of the viral glycoprotein to mediate cell-cell fusion or affect virus infectivity. In contrast, each of the other mutations, except for the Ile-to-Ala change, completely inhibited the ability of the glycoprotein to fuse HeLa-T4 cells and of mutant virions to infect H9 cells. The alanine mutation produced an intermediate phenotype in which both cell fusion and infectivity were significantly reduced. Thus, the biological activity of the glycoprotein titrates with the hydrophobicity of the residue in this position. None of the mutations affected the synthesis, oligomer formation, transport, or processing of the HIV glycoprotein complex. Although these results do not rule out a role for the leucine zipper region in glycoprotein oligomerization, they clearly point to a critical role for it in a post-CD4 binding step in HIV membrane fusion and virus entry.
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PMID:Mutations in the leucine zipper of the human immunodeficiency virus type 1 transmembrane glycoprotein affect fusion and infectivity. 162 54

The external glycoproteins of human immunodeficiency virus type 1 (HIV-1) (gp120) and HIV-2 (gp105) are responsible for binding the cellular receptor CD4. The proteins are functionally identical although their affinity for CD4 varies, with gp120 binding 10- to 20-fold more efficiently than gp105. To investigate the structural requirements for CD4 binding in each molecule we have constructed a number of hybrid glycoproteins in which sequences are exchanged between the two molecules via conserved residues and subsequently tested for their ability to bind to CD4. We found that two constructs in which the V1/V2 or V3 loops of gp105 are exchanged for those of gp120 continue to bind to CD4. Surprisingly, however, all other domain exchange mutants failed to bind to CD4 suggesting that long-range interactions within the molecule are sequence-specific. Mixing mutant molecules in vitro did not rescue CD4 binding. However, co-expression of a number of mutant glycoprotein pairs within the same cell produced complementation of CD4 binding ability; complementing molecules were shown to be heteromeric in structure. Alignment of the molecules within each complementation group allowed the interactive sequences necessary for receptor binding to be determined. These sequences constitute a novel target for the disruption of gp120 function.
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PMID:Complementation of human immunodeficiency virus glycoprotein mutations in trans. 164 36

The antiviral activity of 6-0-butanoylcastanospermine (MDL 28,574) [50% inhibitory concentration (IC50: 1.1 microM)] in JM cells infected with a recent isolate of HIV-1 (GB8), was compared with other inhibitors of glycoprotein-processing enzymes. N-butyldeoxynojirimycin (BuDNJ), deoxynojirimycin (DNJ), castanospermine (CAST) or the reverse transcriptase inhibitor 2'3'-dideoxycytidine (ddC) had activities of 56, 560, 29 and 0.1 microM, respectively. MDL 28,574 was at least 50 times more active than BuDNJ and less active but better tolerated in cell culture than ddC, two compounds currently undergoing clinical trials. The CAST derivative showed good protection in H9 cells infected with HIV-1 (RF; IIIB; U455), and HIV-2 (ROD), although the potency was less than that seen in the JM/GB8 system. HIV-1 glycoproteins, gp160 and gp120, synthesized in H9 cells chronically infected with HIV-1 (RF) and treated with MDL 28,574, were characterized by an increase in relative molecular weight of approximately 7-8000 kD. The ratio of gp120 to gp160 was markedly reduced in treated cells and provided further evidence that cleavage of the gp160 precursor molecule is a major consequence of the inhibition of glycoprotein processing. The intracellular target for MDL 28,574 was verified as alpha-glucosidase-I of the processing enzymes by the analysis of high-glucose glycopeptides recovered from treated mouse cells. This activity correlated with the antiviral effect observed against the growth of a mouse retrovirus, Moloney murine leukemia virus (MOLV), in mouse cells.
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PMID:6-0-butanoylcastanospermine (MDL 28,574) inhibits glycoprotein processing and the growth of HIVs. 165 79

In a study on the evolution of genomic diversity of HIV-1, genomic RNA was isolated from serum of two individuals. Starting at the time of primary infection we collected six samples of serum from each patient over a period of 5 years. Ninety-four cDNA clones (50 of patient 1 and 44 of patient 495) of part of the envelope coding region including the principal neutralization domain (PND) were sequenced. Around the time of antibody seroconversion, genomic RNA levels reached a peak and the population of sequences was highly homogeneous. In the course of the infection, the number of amino acid substitutions accumulated, which led to a higher genomic diversity within successive samples and a drift in the consensus sequence, progressively differing from the first found consensus sequence. Fixation of a substitution at glycoprotein 120 amino acid 308 was observed in both patients between two time points (patient 1, H----P; patient 495, P----H). With the use of 16-meric synthetic peptides, differing only at the 308 position (H308 versus P308), antibody binding specificity was found to be dependent on this difference. In patient 495, the nonconservative (P308----H) substitution reduced the binding affinity with the patient's antibodies. Furthermore, antibody competition assays showed that the observed substitution at position 308 elicited a new antibody population, indicating antigenic variation. After the decline of V3-specific antibodies, the simultaneous increase in genomic RNA levels and progression to AIDS in patient 495, a new variant with major changes in the PND emerged, again forming a homogeneous population of sequences.
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PMID:Naturally occurring mutations within HIV-1 V3 genomic RNA lead to antigenic variation dependent on a single amino acid substitution. 165 85

Apparently conflicting results have been reported regarding the role of env glycoprotein glycans in human immunodeficiency virus type 1 (HIV-1) infectivity and cytopathogenicity. Whereas we have shown that enzymic removal of carbohydrates from mature envelope glycoproteins has only limited effect on the ability of HIV-1 to bind to CD4 and to infect target cells, sugar analogues that interfere with the glycosylation process of the nascent molecule markedly reduce virus infectivity. Here we have investigated the effect of a glucosidase inhibitor, 1-deoxynojirimycin (dNM), on the bioactivity and immunoreactivity of precursor gp160 produced by recombinant vaccinia virus-infected BHK-21 cells (rgp160). dNM (4 mM) did not affect the amount of rgp160 recovered nor its secretion from the cells. As described by other authors the effect of dNM was incomplete, resulting in the production of rgp160, the glycosylation of which was heterogeneous with respect to apparent Mr distribution and to sensitivity to endoglycosidase H and endoglycosidase F, all the species being susceptible to N-glycanase. A major reduction of the binding to CD4+ cells was noted with rgp 160 produced by dNM-treated cells using a quantitative indirect immunofluorescence assay and labelling with polyclonal human anti-HIV IgG. Similarly, dNM treatment altered the accessibility to murine monoclonal antibody 110-4 of the exposed V3 loop of HIV-1 gp120 by at least 10-fold, as determined by either ELISA capture assay or immunoaffinity purification. Such bioactivity and conformation modifications, which result from the abnormal folding of the nascent glycoprotein due to aberrant glycosylation, may account for the impaired HIV-1 infectivity elicited by dNM.
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PMID:Effect of a glucosidase inhibitor on the bioactivity and immunoreactivity of human immunodeficiency virus type 1 envelope glycoprotein. 167 78

The CD2 T lymphocyte glycoprotein surface molecule mediates both cell to cell adhesion and T cell activation, two processes that are involved in the spread of HIV infection. Treatment of chronically HIV-infected PBMC with anti-CD2 mAb has been shown to induce the expression of infectious virus from these cultures. In this study we investigated the mechanisms whereby anti-CD2 antibodies stimulate viral production. We demonstrate that treatment of transiently transfected T lymphocytes with anti-CD2 antibodies results in activation of the HIV long terminal repeat. Furthermore, CAT assays using mutated HIV long terminal repeat-CAT constructs and gel shift assays demonstrate that this activation is dependent on the NF-kappa B enhancer. These studies suggest that interaction of CD2 with its natural ligand, LFA-3, may play a role in regulation of HIV expression.
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PMID:Anti-CD2 receptor antibodies activate the HIV long terminal repeat in T lymphocytes. 168 Sep 14


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