Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA clone corresponding to the gp41 gene fragment nucl. 7573-7730 of the human immunodeficiency virus type 1 (HIV-1) was selected from a random HIV-1 genomic library expressed in yeast. This clone encodes a 52-residue long peptide (amino acid (a.a.)) 591-642) bearing the major immunodominant domain (a.a. 598-609) of the HIV-1 transmembrane glycoprotein gp41. Expression of the recombinant peptide pSE-env591-642 was driven by the alpha-mating factor leader sequence contained in a plasmid pSE-x allowing the synthesis and secretion of foreign gene product in Saccharomyces cerevisiae. Time-course analysis of the secretion into culture medium revealed an optimal production of the glycoprotein fragment at 28-30 h with no observable cytotoxicity. The secreted peptide is highly glycosylated with NH2-terminal heterogeneity probably due to different post-translational modifications. The secreted peptide shows an extreme antigenicity since in ELISA assays, as few as 5 microliters/well of crude supernatant are sufficient to obtain a strong detection by monoclonal antibodies or by 100% of sera from HIV-infected individuals. The purified glycopeptide pSE-env591-642 binds to a monoclonal antibody directed against the immunodominant epitope (a.a. 603-609) with an affinity similar to that of the complete glycoprotein gp160 (Kd values within the 10(-10) M range) and with a 100-fold higher affinity than that of a linear peptide fragment SP-env584-609. These results indicate that overexpression in yeast can efficiently provide an abundant source of highly antigenic gp41 protein fragment pSE-env591-642 which retains the antigenic properties of the native gp160 protein. Such a recombinant peptide should therefore be considered as a good candidate for antigen in HIV detection tests.
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PMID:Expression in yeast of a cDNA clone encoding a transmembrane glycoprotein gp41 fragment (a.a. 591-642) bearing the major immunodominant domain of human immunodeficiency virus. 186 70

The transmembrane glycoprotein (gp41 or TM) of HIV-1 contains limited sequence similarity to TM of some immunosuppressive animal retroviruses. A specific HIV-1 TM sequence, denoted CS3, inhibits T-cell activation in vitro and antibody specific to CS3 has been linked to the absence of disease. CS3, when conjugated to human serum albumin (HSA) and labeled with fluorescein, binds specifically to CD4+ cell lines. Cross-linking of CS3-HSA to its binding activity on the CD4+ cell line RH9 reveals a putative subunit size of approximately 44 kD. Incubation of RH9 cells with CS3-HSA prior to addition of HIV-1 prevented HIV-1-mediated cell lysis and inhibited infection. These results suggest that the CS3 region of TM plays an important role in the pathogenesis of the AIDS virus, HIV-1.
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PMID:Characterization of a putative cellular receptor for HIV-1 transmembrane glycoprotein using synthetic peptides. 197 67

An integral transmembrane glycoprotein of the Human Immunodeficiency Virus (HIV) is gp 41. Five peptides (P1, P2, P3, P4, and P5) containing a conserved region of the gp 41 molecule have been synthesized. We tested P3, P4 and P5 for their effects on short-circuit current (Isc) across rat colonic mucosa. All three peptides increased the Isc; P5 was the most potent agonist. Serosal pretreatment of tissues with the chloride transport inhibitor, bumetanide (0.1 mM) or chloride replacement with gluconate, inhibited the response, suggesting that the increase in Isc was due to stimulation of active chloride secretion. The synthetic somatostatin analog octreotide (0.1 mM) also inhibited (P less than .05) the response to P5 (1 microM). The data provide a possible rationale for one aspect of the efficacy of octreotide in treating secretory diarrhea in patients with Acquired Immunodeficiency Syndrome (AIDS).
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PMID:Peptides of human immunodeficiency virus (HIV) evoke rat colonic electrolyte secretion inhibitable by the somatostatin analog octreotide. 199 Feb 29

A rapid whole blood test has been developed for circulating antibodies to human immunodeficiency virus type 1 (HIV-1), based on agglutination of autologous red blood cells. Evaluation of the test revealed that 100% of seropositive HIV-1 patients (both asymptomatic and AIDS cases) were detected (n = 94) with a specificity of 99.5% in healthy blood donors (n = 596). The assay uses an Fab fragment of a monoclonal antibody specifically directed against glycophorin (a transmembrane glycoprotein present on the surface of human red blood cells). This anti-red blood cell Fab is conjugated via the inter-heavy chain cysteines to a synthetic peptide corresponding to the immunodominant epitope of the HIV-1 viral coat protein gp41 (579-613). Addition of this reagent to 10 microliters of whole blood results in the Fab-peptide conjugate coating the red blood cells with peptide. In the presence of circulating antibodies to the HIV-1 peptide, red cell agglutination occurs within 2 min. The sensitivity and specificity of this reagent indicate that it is appropriate for use as a rapid diagnostic test for HIV-1 seropositivity.
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PMID:Rapid whole blood assay for HIV-1 seropositivity using an Fab-peptide conjugate. 201 40

Four of eight human monoclonal antibodies (huMAbs) to gp41 were identified which could enhance human immunodeficiency virus type 1 (HIV-1) infection in vitro by complement-mediated antibody-dependent enhancement (C'-ADE). These enhancing huMAbs were mapped to two distinct domains on the HIV-1 gp41 transmembrane glycoprotein by using synthetic peptides. The first domain, amino acids 579 to 613 (peptide AA579-613), was recognized by three of the four enhancing huMAbs. The AA579-613 peptide blocked C'-ADE of HIV-1 infection in vitro whether it was mediated by these three huMAbs or by human polyclonal anti-HIV serum. The second domain, amino acids 644 to 663, bound the remaining enhancing huMAb. This peptide weakly blocked C'-ADE mediated by the huMAb and by an HIV immune globulin fraction but did not block C'-ADE mediated by a patient's serum. The patient's serum did react with the peptide in an enzyme immunoassay. The huMAbs to the two domains could interact in vitro to enhance HIV-1 infection in a synergistic manner. These two domains, which bind enhancing antibodies, are conserved between HIV-1 isolates as well as between HIV-2 and simian immunodeficiency virus isolates. These data demonstrate the existence of two conserved regions within the HIV-1 gp41 which bind enhancing antibodies; these two domains, amino acids 579 to 613 and 644 to 663, may prove important in HIV-1 vaccine development and in immunopathogenesis of HIV-1 infection.
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PMID:Two immunodominant domains of gp41 bind antibodies which enhance human immunodeficiency virus type 1 infection in vitro. 207 48

The effect of 11 derivatives of 1-deoxynojirimycin (DNM) on the replication of HIV-1 was studied. Compared with DNM, seven of them showed remarkable inhibition of HIV-1-induced syncytium formation at significantly low concentrations which were not cytotoxic. Two derivatives were found to markedly reduce the infectious virus yields from cell lines chronically infected with HIV. Analysis of HIV-1 envelope glycoproteins showed that the derivatives induced modification of the processing of not only gp120/160 but also the transmembrane glycoprotein gp41. The modification of the processing of the transmembrane glycoprotein gp41 might play an important role in the inhibition of virus replication at a step after the binding of gp120 to CD4. The enhanced anti-HIV activity of DNM derivatives reported here could increase the possibility of non-toxic therapeutic intervention in HIV infections.
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PMID:Inhibitory effect of novel 1-deoxynojirimycin derivatives on HIV-1 replication. 214 90

The interaction of 11 overlapping synthetic peptides corresponding to N-terminal segment of HIV transmembrane glycoprotein gp41 (fusion domain) with artificial lipid membranes has been studied. For this purpose the increase of a bilayer lipid membrane (BLM) conductivity and the changes in ESR spectra of spin-labelled liposomes were registrated. Peptide fragment 523-532 gp160 (BRU strain) had the critical length with regard to channel-forming activity on BLM. The degree of such membranotropic action increased simultaneously with the growth of peptide length and the temperature in the cell. Peptides 518-532 and 517-532 lysed TEMPOcholine-containing liposomes at 37 degrees C. The significance of observed effects for explanation of the mechanism of HIV-induced membrane fusion is discussed.
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PMID:Interaction of human immunodeficiency virus (HIV-1) fusion peptides with artificial lipid membranes. 217 85

The CD4 antigen is the high affinity cellular receptor for the human immunodeficiency virus type-1 (HIV-1). Binding of recombinant soluble CD4 (sCD4) or the purified V1 domain of sCD4 to the surface glycoprotein gp120 on virions resulted in rapid dissociation of gp120 from its complex with the transmembrane glycoprotein gp41. This may represent the initial stage in virus-cell and cell-cell fusion. Shedding of gp120 from virions induced by sCD4 may also contribute to the mechanism by which these soluble receptor molecules neutralize HIV-1.
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PMID:Dissociation of gp120 from HIV-1 virions induced by soluble CD4. 192 47

An 80-kilodalton glycoprotein (gp80) was produced in human immunodeficiency virus type 2 (HIV-2)-infected cells along with three envelope glycoproteins that we have recently reported: the extracellular glycoprotein (gp125), the envelope glycoprotein precursor (gp140), and the transient dimeric form of the precursor (gp300). gp125 and gp80 were detectable after the synthesis of gp140 and the formation of gp300. Using a specific monoclonal antibody, we showed here that gp80 is a dimeric form of the transmembrane glycoprotein gp36 of HIV-2. Dimerization of the envelope glycoprotein precursor and dimeric forms of the transmembrane glycoproteins were also observed in cells infected with simian immunodeficiency virus (SIV-mac), a virus closely related to HIV-2. Under routine conditions of our experiments (i.e., extraction by 1% Triton X-100 before polyacrylamide gel electrophoresis in sodium dodecyl sulfate [SDS]), monomeric forms of the transmembrane glycoprotein of HIV-2 and SIV-mac were only seldomly observed. Dimeric forms of the envelope precursors and the transmembrane glycoproteins are probably stabilized by extraction in the nonionic detergent Triton X-100 since such dimeric forms resist dissociation during subsequent electrophoresis in the presence of the ionic detergent SDS. However, the dissociation of these dimeric forms might occur when samples are prepared by extraction directly in 1% SDS or by incubation of the purified dimers at acidic pH. Dimerization of the envelope precursor might be required for its processing to give the mature envelope proteins, whereas the transmembrane dimer might be essential for optimal structure of the virion and thus its infectivity.
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PMID:Transmembrane envelope glycoproteins of human immunodeficiency virus type 2 and simian immunodeficiency virus SIV-mac exist as homodimers. 229 88

Three of 16 human monoclonal antibodies (hu-mAbs) enhanced human immunodeficiency virus type 1 (HIV-1) infection of MT-2 target cells by means of a mechanism that is dependent on complement. Enhanced infections are characterized by an increase in cytopathic effects and antigen synthesis as well as an increase in the production of progeny virus as detected by release of reverse transcriptase activity and infectious virus into the culture medium. Analyses by radioimmunoprecipitation, Western blot, and ELISA using the pENV9 envelope fragment localize the antigenic specificities of these three hu-mAbs to the N-terminal two-thirds of the transmembrane protein gp41. Competitive binding experiments indicate that the hu-mAbs are reactive with immunodominant epitopes of gp41 recognized by sera from essentially all HIV-1-infected subjects. Combination dose-effect experiments demonstrate that these hu-mAbs can act synergistically in vitro to enhance HIV-1 infection. These data demonstrate that hu-mAbs directed against the HIV-1 transmembrane glycoprotein gp41 can enhance HIV-1 infection in vitro. The availability of these reagents allows for the mapping of enhancing epitopes on HIV-1 and provides a means for studying whether deletion of such enhancing epitopes from candidate HIV-1 vaccines might improve the protective immune response to HIV-1 in immunized humans and chimpanzees.
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PMID:Human monoclonal antibodies to the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 enhance HIV-1 infection in vitro. 232 77


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