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)

Antibodies of individuals infected with the human immunodeficiency virus type 1 (HIV-1) were used to probe the antigenicity of the HIV-1 transmembrane protein of 41 kD (gp41) by antibody-reactive peptide scanning (Pepscan). Eleven distinct sequential antibody-binding sites were defined by testing reactivity to 339 overlapping nonapeptides spanning the complete gp41 amino acid sequence. Such analysis only maps continuous antibody-binding sites of nine amino acids in length and does not identify putative discontinuous or assembled epitopes. Three B cell epitopes (aa 609-622; aa 655-699; aa 664-681) at the amino-terminal border of the putative transmembrane anchor and two (aa 732-748; aa 744-762) at the carboxyl-terminal border of this domain were the most antigenic. One antibody-binding domain (aa 834-852) with four amino acids homologous to the beta-1 domain of HLA class II beta-chain was recognized by the serum in 1 of 4 AIDS patients tested and not by any of the eight sera from symptom-free individuals. Although functional domains of gp41 involved in virus replication, cytopathicity and possibly immunosuppression were shown to bind antibodies of HIV-1-infected individuals, no relationship between antibody recognition patterns and disease progression was apparent.
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PMID:Map of sequential B cell epitopes of the HIV-1 transmembrane protein using human antibodies as probe. 170

Monoclonal antibody SF8/5E11, which recognizes the transmembrane protein (TMP) of simian immunodeficiency virus of macaque monkeys (SIVmac), displayed strict strain specificity. It reacted with cloned and uncloned SIVmac251 but not with cloned SIVmac142 and SIVmac239 on immunoblots. This monoclonal antibody neutralized infection by cloned, cell-free SIVmac251 and inhibited formation of syncytia by cloned SIVmac251-infected cells; these activities were specific to cloned SIVmac251 and did not occur with the other viruses. Site-specific mutagenesis was used to show that TMP amino acids 106 to 110 (Asp-Trp-Asn-Asn-Asp) determined the strain specificity of the monoclonal antibody. This strain-specific neutralizing determinant is located within a variable region of SIVmac and human immunodeficiency virus type 2 (HIV-2) which includes conserved, clustered sites for N-linked glycosylation. The determinant corresponds exactly to a variable, weak neutralizing epitope in HIV-1 TMP which also includes conserved, clustered sites for N-linked glycosylation. Thus, the location of at least one neutralizing epitope appears to be common to both SIVmac and HIV-1. Our results suggest a role for this determinant in the viral entry process. Genetic variation was observed in this neutralizing determinant following infection of a rhesus monkey with molecularly cloned SIVmac239; variant forms of the strain-specific, neutralizing determinant accumulated during persistent infection in vivo. Selective pressure from the host immune response in vivo may result in sequence variation in this neutralizing determinant.
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PMID:Strain-specific neutralizing determinant in the transmembrane protein of simian immunodeficiency virus. 170 94

Immunoreactive regions of human immunodeficiency virus type 1 (HIV-1) gp41 were mapped by reacting HIV-1 antibody-positive human sera with overlapping synthetic peptides which covered the transmembrane protein. Three immunoreactive domains were identified, and five different and partially overlapping epitopes recognized by HIV-1-positive human sera were found within one immunodominant region. The effect on antibody recognition after single amino acid substitutions within one defined epitope was also studied. The reactivity of various HIV-1-positive sera to synthetic peptides with amino acid substitutions representing known isolates suggests an important substitution in the major epitope of African HIV-1 strains.
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PMID:Continuous epitopes of the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein and reactivity of human sera to synthetic peptides representing various HIV-1 isolates. 170 85

This article reviews the basic method used to define native epitopes from transmembrane proteins and the function of synthetic peptides in HIV screening and typing. Identification of continuous native epitopes from structural protein sequences of HIV-1 and HIV-2 involves the use of systematic scanning epitope technology. Scanning profiles of these two types of HIV demonstrated that there is a highly immunoreactive continuous native epitope region in the transmembrane protein gp41 of HIV-1 as well as in the corresponding region in HV-2 gp34. However, the number of highly immunoreactive regions differs in the structural proteins of the two types of HIV infections. These highly immunoreactive regions, when presented accurately as synthetic antigens in solid-phase enzyme immunoassay, can provide tests that are remarkably appropriate for the early and reliable diagnosis and type-specification of HIV-1 and HIV-2 infections.
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PMID:Synthetic peptides in HIV antibody screening and typing. 171 28

We investigated the antigenicity of a highly conserved region in the transmembrane protein of the human immunodeficiency virus type 1 (HIV-1). In order to identify antigenically important residues, amino-acid sequences of synthetic peptides representing this region were varied systematically: single residues were omitted from the sequence of HIV-env 583-599; threonines were substituted for pairs of residues in HIV-env 581-599; the sequences of heptadeca-peptides were shifted by single residues. The peptides were tested in an enzyme immuno-assay against fourteen HIV-1 antibody-positive human sera, which were previously found to react with HIV-env 583-599, and against rabbit antisera to the peptides HIV-env 583-599 and 586-606. Substitutions as well as deletions in the sequence 589-596 (AVERYLKD) aborgated the antigenicity of the peptides with most of the human sera. Changes outside this sequence affected the reactivities differentially. Six overlapping dodeca-peptides, shifted in the sequence by single residues, lacked antigenicity in a competition assay, suggesting antigenic dependence on an ordered peptide conformation, which the longer peptides may preferentially assume. 19- and 21-mers with overlapping sequences competed to different extents with each other for binding to the antibodies of 3 human sera, illustrating that more than one antigenic structure in this narrow region can be recognized by a single polyclonal serum.
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PMID:A cluster of continuous antigenic structures in the transmembrane protein of HIV-1: individual patterns of reactivity in human sera. 171 46

Immunogenic regions of the gp41 transmembrane protein of human immunodeficiency virus type 1 (HIV-1) were previously mapped by examining polyclonal sera from HIV-infected patients and rodent polyclonal and monoclonal antibodies (MAbs) to peptides of gp41. To define the epitopes within these regions to which infected humans respond during the course of infection, the specificity of human MAbs to these regions had to be studied. Using 10 human MAbs identified initially by their reactivity to whole gp41 in HIV-1 lysates, the epitopes within the immunodominant region of gp41 and within a second immunogenic region of gp41 have been mapped. Thus, five MAbs (from five different patients) to the immunodominant domain of gp41 in the vicinity of the cysteines at positions 598 and 604 (hereinafter designated cluster I) reacted with a stretch of 11 amino acids from positions 590 to 600. Four of these five MAbs were reactive with linear epitopes, while one MAb required the conformation conferred by the disulfide bridge between the aforementioned cysteines. Three MAbs to cluster I revealed dissociation constants ranging from 10(-6) to 10(-8) M, depending on the MAb tested and the size of the synthetic or recombinant peptide used in the assay. Five additional MAbs reacted with a second immunogenic region between positions 644 and 663 (designated cluster II). Four of these five MAbs were specific for conformational determinants. Titration of sera from HIV-infected patients showed that there was about 100-fold more antibody to cluster I than to cluster II in patients' sera, confirming the immunodominance of cluster I.
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PMID:Epitope mapping of two immunodominant domains of gp41, the transmembrane protein of human immunodeficiency virus type 1, using ten human monoclonal antibodies. 171 20

Eighteen monoclonal antibodies (MAb) to simian immunodeficiency virus (SIV) envelope have been characterized. All MAb were shown to bind to viral antigens on the surface of unfixed SIV-infected cells and to precipitate surface glycoproteins of SIVmac251. In Western blot 11 MAb bound to gp160 and gp120, five bound to gp160 and the transmembrane protein gp41 and two MAb did not react with denatured antigen. Preliminary competition assays identified the existence of six competition groups; two groups were within gp41 and four were within gp120. Of the latter four groups, three contained MAb with neutralizing activity. Two of the neutralizing MAb (KK5 and KK9) did not react with denatured antigen in Western blot suggesting that they may recognize conformational epitopes. Enzyme-linked immunosorbent-assay titres of MAb against SIVmac251 ranged from 10(2.4) to 10(5.6) and although similar titres were obtained with some MAb against other SIV and HIV antigens, the presence of isolate specific and shared group epitopes was demonstrated.
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PMID:Production and of monoclonal antibodies to simian immunodeficiency virus envelope glycoproteins. 171 42

A sheep was immunized with a synthetic peptide corresponding to amino acid residues 586-606 of the precursor envelope protein GP-160 of the HIV-1 including a conserved epitope region of the GP-41 transmembrane protein in the mature viral particles, referred to as SM 284 HIV-1 [1]. It is demonstrated that immune RNA extracted from the lymphoid organs of the immunized animal (SM 284 HIV-1 I-RNA) was able to transfer immune cellular reactivity to SM 284 HIV-1 in vitro to human and rabbit lymphocytes and in vivo to Cebus apella monkeys. The transfer was detected by the leukocyte adherence inhibition test (LAI) as an indicator of cellular reactivity. One of the most relevant results was the demonstration that SM 284 HIV-1 I-RNA was able to induce cellular immunological memory in vivo in monkeys. These results may be relevant to delineate a new alternative for immunomodulation against HIV infection.
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PMID:RNA-mediated transfer of cellular immunity to a synthetic env antigen of the human immunodeficiency virus (HIV-1). 172 67

We established seven hybridoma clones producing monoclonal antibodies (MAbs) against the envelope transmembrane protein (TMP) of a Ghanian isolate of human immunodeficiency virus type 2 (HIV-2[GH-1]) from mice immunized with the detergent-disrupted purified whole virus. The MAbs were found to react with 35 kilodalton (kD) TMP of the HIV-2[GH-1] virus in a Western blot assay (WB). Two of these MAbs recognized 135 kD proteins in addition to TMP in the lysate of HIV-2[GH-1]-infected cells. Two other MAbs cross-reacted with viral components corresponding to TMPs of HIV-2ROD and SIVMAC isolates in a Western blot. Results of competitive binding assay suggest that there are at least three epitopes on a TMP molecule of the HIV-2[GH-1] isolate. The MAbs did not inhibit syncytium formation between HIV-2[GH-1]-infected MOLT-4 cells and MOLT-4 clone 8 cells, nor virus infection to MOLT-4 clone 8 cells.
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PMID:Production and characterization of mouse monoclonal antibodies against the transmembrane protein of a human immunodeficiency virus type 2. 172 59

DNA sequence analysis was performed on a 235-bp region of the p21 e transmembrane protein gene of the human T-cell lymphoma/leukemia virus type I (HTLV-I) which encompassess the putative immunosuppressive peptide. Polymerase chain reaction-based amplification was used to generate multiple molecular clones from isolates derived from fresh or cultured cells from 19 individuals. A dendrogram was constructed using the p21e DNA sequence information to compare the sequences among isolates in the current study and other previously published HTLV-I isolates including strains from Africa and Papua New Guinea. Examination of multiple clones from individual isolates revealed the presence of multiple genotypes in patients with tropical spastic paraparesis/HTLV-I-associated myelopathy and adult T-cell leukemia/lymphoma. These findings suggest that HTLV-I, like HIV, may be present as a quasispecies in vivo. Our studies, however, failed to identify specific sequence motifs that segregated exclusively with the lymphoproliferative or neurological forms of the disease.
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PMID:DNA sequence analysis of the gene encoding the HTLV-I p21e transmembrane protein reveals inter- and intraisolate genetic heterogeneity. 173 4


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