UMLS:C0019693 - FACTA Search

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

Numerous studies have established the correlation between antibodies to the core protein p24 of HIV-1 and the progression of the acquired immunodeficiency syndrome. In this study, we analyzed the immune response to two recombinant gag proteins, p24 and p17, in order to evaluate their diagnostic or prognostic significance. Immune response to the immunodominant domain of the transmembrane glycoprotein gp41 was used as a reference. Sera collected from individuals from France and Burundi (Central Africa) at various CDC stages of HIV-1 infection were tested using three sandwich enzyme-linked immunoassays developed with a synthetic peptide corresponding to the immunodominant domain of gp41, SP gp41, or recombinant p24 and p17 cloned and expressed in Escherichia coli. These assays allowed detection of titer antibodies to the three cited antigens. Antibodies to SP gp41 were detected in every HIV-1-positive patient from France and Burundi, generally at a high and stable level. Results obtained with p24 confirmed the value of antibodies to p24 as a prognostic marker only in European and North American populations, since the African population had very high levels of these antibodies even at an advanced stage of the disease. They also confirmed that initial antibody response to p24 is more predictive of outcome than antibody titer change over time. Although antibodies to p17 decline during progression to AIDS, they are frequently absent in French patients at early, asymptomatic stages and therefore could not be used as a prognostic marker. In contrast, antibodies to p17 are significantly less common in African patients with AIDS when compared with symptomless HIV-1-infected African individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence and persistence of antibody titers to recombinant HIV-1 core and matrix proteins in HIV-1 infection. 831 75

vpu, alone among the genes of human immunodeficiency virus type 1 (HIV-1), is unique to this virus, with no analogous reading frame evident in the genomes of either HIV-2 or the related SIVs. Effects of vpu upon levels of virus production from infected cells have been noted, but vpu is dispensable for HIV-1 replication in vitro and its significance in the natural viral life cycle is unclear. We have now identified and characterized a major influence of vpu upon the growth and host cell range of a cloned recombinant HIV-1. This effect required the presence of a second determinant mapping to the 3' end of the env gene, and was not detected in clones incorporating an env gene derived from a different strain of the virus. This indicates that important effects of vpu may have been lost in some experimental systems because of the particular viruses used, and further suggests the involvement of a determinant in the transmembrane glycoprotein of the virus in the action of vpu.
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PMID:Changes in the host range and growth potential of an HIV-1 clone are conferred by the vpu gene. 831 2

Deletions of the major variable regions (V1/V2, V3, and V4) of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein were created to study the role of these regions in function and antigenicity. Deletion of the V4 region disrupted processing of the envelope glycoprotein precursor. In contrast, the deletion of the V1/V2 and/or V3 regions yielded processed exterior envelope glycoproteins that retained the ability to interact with the gp41 transmembrane glycoprotein and the CD4 receptor. Shedding of the gp120 exterior glycoprotein by soluble CD4 was observed for the mutant with the V3 deletion but did not occur for the V1/V2-deleted mutant. None of the deletion mutants formed syncytia or supported virus entry. Importantly, the affinity of neutralizing antibodies directed against the CD4-binding region for the multimeric envelope glycoprotein complex was increased dramatically by the removal of both the V1/V2 and V3 structures. These results indicate that, in addition to playing essential roles in the induction of membrane fusion, the major variable regions mask conserved neutralization epitopes of the HIV-1 gp120 glycoprotein from antibodies. These results explain the temporal pattern associated with generation of HIV-1-neutralizing antibodies following infection and suggest stratagems for eliciting improved immune responses to conserved gp120 epitopes.
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PMID:Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions. 833 23

The presence of specific IgA antibodies in sera from 25 infants born to HIV-1 seropositive mothers was investigated by peptide-ELISA and peptide time-resolved fluoro-immunoassay (TR-FIA). The infants had been monitored at different times after birth for clinical signs and/or symptoms of HIV-1 infection and for detection of HIV-1 in lymphocyte cultures. Serum samples had also been tested for HIV-1 IgG antibodies by commercial ELISA and Western blot and for p24 antigen. Eleven of 25 children were then identified as infected. IgA detection was performed after rProtein G treatment to remove interfering IgG. In the infected group, IgA specific antibodies to a synthetic peptide representing a highly conserved region of the transmembrane glycoprotein gp41 (env: 594-613) were detected in 27 (73%) out of 37 serum samples (9 of 11 children) by the peptide-ELISA test. IgA specific antibodies to the same peptide were found in 30 (81%) sera (9 of 11 children) by the peptide-TR-FIA. Specific HIV-1 IgA antibodies were detected as early as 2 months of age in serum samples from five out of seven children (71% sensitivity) using peptide-ELISA and from six out of seven (86% sensitivity) by peptide-TR-FIA. Conversely, IgA specific antibodies to HIV-1 were absent in two infected children as well as in the sera of all uninfected children tested during the follow up period. Since maternal IgA does not cross the placenta, IgA detection in the serum of the infant is indicative of HIV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early detection of IgA specific antibodies in HIV-1 infected children by peptide-ELISA and peptide time-resolved fluoro-immunoassay. 833 15

Molecular mimicry of major histocompatibility (MHC) antigens by viral glycoproteins has been suggested as one of the possible mechanisms of induction of an autoimmune response by human immunodeficiency viruses. A monoclonal antibody (M38) was previously shown to bind to both human immunodeficiency virus type 1 (HIV-1) gp120 and beta-2 microglobulin-free HLA class I heavy chains encoded by an HLA C allele. Using HLA C recombinant proteins and synthetic peptides, the M38 class I binding site was mapped to a stretch of 44 amino acids of the alpha 1 domain. The amino acid residues recognized are clustered in two non-contiguous regions at positions 66-69 (KYKR) and 79-82 (RKLR) shared by almost all HLA C alleles. On HIV-1 gp120, M38 binds to two non-contiguous sequences (KYK and KAKR) at positions 490-492 and 505-508 located at the edges of a large hydrophobic region that is apparently involved in binding the transmembrane glycoprotein gp41. The C-terminal gp120 M38-reactive region (KAKR) lies within the immunodominant sequence APTKAKRRVVQREKR, against which the majority of HIV-infected individuals produce antibodies. The results indicate that a functionally important region of HIV-1 gp120 shares similar amino acid sequence motifs with the antigen recognition site of most HLA class I C alleles. The molecular mimicry may be the basis for autoimmune responses in HIV infection.
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PMID:Human immunodeficiency virus type 1 gp120 C5 region mimics the HLA class I alpha 1 peptide-binding domain. 834 67

The performance of a competitive EIA for the detection of HIV-2-specific antibody utilising a viral lysate antigen was assessed over a 3 year period in The Gambia, West Africa, and compared with a commercially available assay, ELAVIA-2, using three panels of sera. An immunodominant region of the transmembrane glycoprotein of an HIV-2 isolate (ANT 53) was also cloned and expressed in E. coli as a beta-galactosidase fusion protein and the resulting recombinant protein substituted in place of the existing viral lysate antigen. Competitive EIAs were found to be both a specific and sensitive means of reliably determining the HIV-2 status of an individual with a high predictive value, particularly when a strategy of concordant positive results in the two EIAs was used. When either anti-HIV-2 competitive EIAs were used in conjunction with a competitive EIA for anti-HIV-1 detection it was possible in the vast majority of cases to identify the virus-type infecting an individual and speciate HIV-1 and HIV-2 infections. A few sera which showed similar regression profiles when diluted over a serial tenfold dilution steps were identified as possible dual infections.
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PMID:Competitive EIA for anti-HIV-2 detection in The Gambia: use as a screening assay and to identify possible dual infections. 848 35

We recently demonstrated that a single amino acid substitution in matrix residue 12 (12LE) or 30 (30LE) blocks the incorporation of human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins into virions and that this block can be reversed by pseudotyping with heterologous retroviral envelope glycoproteins with short cytoplasmic tails or by truncating the cytoplasmic tail of HIV-1 transmembrane glycoprotein gp41 by 104 or 144 amino acids. In this study, we mapped the domain of the gp41 cytoplasmic tail responsible for the block to incorporation into virions by introducing a series of eight truncation mutations that eliminated 23 to 93 amino acids from the C terminus of gp41. We found that incorporation into virions of a HIV-1 envelope glycoprotein with a deletion of 23, 30, 51, or 56 residues from the C terminus of gp41 is specifically blocked by the 12LE matrix mutation, whereas truncations of greater than 93 amino acids reverse this defect. To elucidate the role of matrix residue 12 in this process, we introduced a number of additional single amino acid substitutions at matrix positions 12 and 13. Charged substitutions at residue 12 blocked envelope incorporation and virus infectivity, whereas more subtle amino acid substitutions resulted in a spectrum of envelope incorporation defects. To characterize further the role of matrix in envelope incorporation into virions, we obtained and analyzed second-site revertants to two different matrix residue 12 mutations. A Val-->Ile substition at matrix amino acid 34 compensated for the effects of both amino acid 12 mutations, suggesting that matrix residues 12 and 34 interact during the incorporation of HIV-1 envelope glycoproteins into nascent virions.
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PMID:Domains of the human immunodeficiency virus type 1 matrix and gp41 cytoplasmic tail required for envelope incorporation into virions. 852 46

The outer membrane glycoprotein gp120 and the transmembrane glycoprotein gp41 are predominant targets of the humoral immune response to infection by human immunodeficiency virus type 1. The third hypervariable region (V3 loop) is the principal neutralizing domain and is the primary target of neutralizing antibodies directed against the envelope proteins of HIV-1. The V3 loop is also the major determinant for HIV-1 cell-specific tropism. To further characterize the humoral immune response directed against the gp120 envelope proteins, we expressed two prototypic gp120 envelope proteins (LAI/HXB2 and ADA) and chimeric gp120 envelope proteins in stable transfected Drosophila melanogaster Schneider 2 cells. Sera from four infected adults over the course of infection [McNearney et al. (1992) Proc. natn. Acad. Sci. U.S.A. 89, p. 10,242] were assayed for reactivity with the respective envelope proteins. Sera obtained at early stages preferentially recognized the gp120 envelope protein ADA, whereas in later stages of infection the sera showed diminished reactivity with both gp120 LAI/HXB2 and gp120 ADA. Chimeric envelope proteins revealed that the humoral response was directed primarily against the V3 loop of gp120 ADA. Furthermore, 22 sera from HIV-1 infected individuals in different stages of the disease were tested. Reactivity of sera with the gp120 envelope protein ADA was seven-fold higher than with the gp120 envelope protein LAI/HXB2. Our results suggest that the humoral immune response is preferentially elicited against the V3 loop of the prototypic macrophage-tropic gp120 envelope protein ADA.
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PMID:Sera from HIV-1 infected individuals in all stages of disease preferentially recognize the V3 loop of the prototypic macrophage-tropic glycoprotein gp120 ADA. 854 53

The effect of a series of synthetic peptides mimicking the N-terminus of HIV transmembrane glycoprotein (gp41) on fusion of negatively charged liposomes consisting of phosphatidylcholine, phosphatidylethanolamine and cardiolipin at a 2:3:5 molar ratio, respectively, has been studied. Peptides P514 and P385 (residue 517-538), lysine and arginine at the C-terminus, respectively, with the amino acid sequence completely corresponding to the N-terminus of gp41 displayed the highest fusogenic activity. The extent of fusion was significantly increased at mild acidic pH (6.0). Acidification particularly influenced the fusogenic activity of P514. Modification of the N- and C-termini of fusion-active peptides by proteins and synthetic polymers blocked the fusion activity. The fusogenic properties of peptides depended on the chain length: P411 consisting of nine hydrophobic amino acid residues had no fusogenic activity, while P415, an 11-member peptide, effectively fused liposomes. The fluorescent probe ANS was used to monitor the hydrophobicity of these peptides. The hydrophobicity of P514 increased appreciably with a change in pH from 6.0 to 7.5. Peptides P514 and P385 induced the leakage of the aqueous contents from liposomes at neutral pH and caused a small, but detectable leakage at acidic pH. Structural and molecular factors influencing the peptide-induced liposome fusion are discussed.
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PMID:[Fusion of negatively-charged liposomes under the effect of peptides from the N-terminal fragment of the HIV-1 transmembrane protein]. 855 67

A potential component that may be useful for passive immunotherapy for HIV-1 is human monoclonal antibodies (HumAbs) possessing potent anti-HIV-1 activity that is directed against conserved regions of the envelope glycoprotein. Such antibodies would, in principle, have the ability to neutralize diverse isolates of HIV-1. To develop such reagents, hybridomas were derived by initial Epstein Barr virus transformation of peripheral blood mononuclear cells (PBMCs) from an asymptomatic HIV-1 seropositive donor followed by fusion with heteromyelomas, and secreted anti-HIV-1 antibodies were further characterized. The specificity of one HumAb, designated as clone 3, was determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses that indicated reactivity to the transmembrane envelope glyco-protein gp41. Synthetic pentadecapeptides overlapping by 10 amino acids were utilized for epitope mapping of clone 3; a decapeptide GCSGKLICTT in the transmembrane gp41 was identified as the epitope. Clone 3 bound to SupT1 cells infected with HTLV-IIIB in fluorescent activated cell sorting analysis. In addition, in vitro biological assays demonstrated that clone 3 possessed neutralization reactivity against diverse laboratory isolates as well as an AZT-resistant isolate. Therefore, clone 3 reactivity defines a conserved neutralizable site on the HIV-1 transmembrane glycoprotein. Clone 3 and the conserved immunogenic epitope on gp41 could be useful in passive and active immunotherapy for the acquired immunodeficiency syndrome (AIDS).
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PMID:A human monoclonal antibody to HIV-1 gp41 with neutralizing activity against diverse laboratory isolates. 867 26

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