Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently demonstrated that human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein precursor gp160 (rgp160) behaves as a mannosyl/N-acetylglucosaminyl (GlcNAc) binding protein. If such a carbohydrate-binding property were of biological relevance it should be shared by other related primate immunodeficiency viruses such as HIV-2. The present study confirms this hypothesis and extends these findings by showing that HIV-2 recombinant gp140 (rgp140) specifically interacts with three affinity matrices substituted by synthetic or natural carbohydrate structures: D-mannose-divinylsulphone-agarose, para-aminophenyl-beta-D-GlcNAc-agarose and the natural glycoprotein, bovine fetuin, also coupled to agarose. Binding of rpg140 to the matrices was inhibited by alpha-D-Man17-BSA (where BSA is bovine serum albumin), beta-D-GlcNAc47-BSA and fetuin, and by glycopeptides derived from pronase-treated porcine thyroglobulin. Glycopeptides obtained after endoglycosidase H treatment of thyroglobulin had a limited inhibitory effect, whereas beta-D-Gal17-BSA and beta-D-glucan had no effect. These results indicate that, like HIV-1 envelope glycoprotein, HIV-2 rgp140 interacts with high-mannose and with the mannosyl core of complex-type N-linked glycans, as well as with the N-acetylglucosaminyl core of oligosaccharidic structures.
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PMID:Mannosyl/N-acetyl-beta-D-glucosaminyl binding properties of the envelope glycoprotein of human immunodeficiency virus type 2. 128 Oct 21

Two antibodies, affinity-purified from human immunodeficiency virus-positive human plasma with synthetic peptides in the region gp41(566-596), were found to recognize oligomeric gp41 more strongly than the monomeric form in an immunoblot assay. In contrast, a murine anti-gp160 monoclonal antibody, which maps within this sequence to gp41(581-596), recognized only monomeric gp41 after disruption of the oligomer with sodium dodecyl sulfate. This monoclonal anti-gp160 antibody did not recognize chemically crosslinked oligomeric gp41 that had been treated with similar conditions used to disrupt the gp41 oligomer. These results indicate that this epitope is inaccessible to binding by this antibody when gp41 is oligomeric. Cyanogen bromide cleavage of gp41 resulted in a 17-kD fragment Thr-541-Met-631. A significant proportion of this fragment was oligomeric when derived from chemically crosslinked gp41. The region Ala-566-Gln-596, within the cyanogen bromide fragment, contains the oligomerization-sensitive epitopes as well as two lysine residues available for crosslinkage. This region is relatively conserved and has the propensity to form an amphipathic alpha-helix.
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PMID:Antibody epitopes sensitive to the state of human immunodeficiency virus type 1 gp41 oligomerization map to a putative alpha-helical region. 128 26

Here, we confirm and extend our previous findings on human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein N-acetylglucosaminyl binding properties. We show the occurrence of saturable, temperature, pH, and calcium dependent carbohydrate-specific interactions between recombinant precursor gp160 (rgp160) and two affinity matrices: D-mannose-divinylsulfone-agarose, and natural glycoprotein, fetuin, also coupled to agarose. Binding of rgp160 to the matrices was inhibited by soluble mannosyl derivatives, alpha-D-Man17-BSA and mannan, by beta-D-GlcNAc47-BSA and by glycopeptides from Pronase-treated porcine thyroglobulin, which produces oligomannose and complex N-linked glycans. Glycopeptides from Endoglycosidase H-treated thyroglobulin partially inhibited rgp160 binding, as did the asialo-agalacto-tetraantennary precursor oligosaccharide of human alpha 1-acid glycoprotein for binding to fetuin-agarose. beta-D-Glucan and beta-D-Gal17-BSA had no or only limited effect. Also, surface unit rgp120 specifically interacted with fetuin-agarose and soluble fetuin, but in the latter case with a twofold reduced affinity relative to rgp160. After affinity chromatography, rgp160 was specifically retained by the two matrices and eluted by mannan in both cases, while rgp120 was not retained by fetuin-agarose but only eluted as a significantly retarded peak, which confirms its specific but weak interaction. Thus, rgp160 interacts with both oligomannose type, and the mannosyl core of complex type N-linked glycans, and its gp120 region plays a role in this interaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carbohydrate binding properties of the envelope glycoproteins of human immunodeficiency virus type 1. 128 14

Inhibitory effects of human immunodeficiency virus (HIV) on T lymphocyte function have been linked to perturbation of signaling through the T cell antigen receptor-CD3 complex. Comparative biochemical analyses of signaling responses were performed in T cells that were either uninfected or chronically infected with the HIV-1/IIIB strain. Stimulation with antibodies to CD3 triggered both Ca2+ accumulation and phosphoinositide hydrolysis responses that were equivalent in uninfected and infected cells. Treatment with anti-CD3 or with phorbol diester also stimulated serine phosphorylation of CD4 molecules in uninfected T cells. However, phosphorylation of CD4 was not observed after anti-CD3 treatment in HIV-infected T cells despite normal phosphorylation responses to phorbol diester. Identical results were obtained using a T cell line that was infected with an env (gp160/120-) HIV-1 defective variant. These studies indicate that infection with HIV-1 inhibits the activation of protein kinase associated with the T cell receptor-CD3 complex by a mechanism which is independent of viral env protein components.
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PMID:Inhibition of T cell antigen receptor-dependent phosphorylation of CD4 in human immunodeficiency virus type 1 infected cells. 131 Sep 88

Efforts to generate a vaccine to prevent infection by human immunodeficiency virus (HIV) have focused on inducing neutralizing antibodies. However, cytotoxic T-lymphocyte (CTL) responses are a major immune defense mechanism required for recovery from many different virus infections. Since CTL epitopes can be defined by short synthetic peptides, we searched for HIV peptides that elicit a viral-specific CTL response in mice. We have developed a new method for screening CTL-inducing peptides involving a single injection into the footpad of mice to prime CTLs in the draining popliteal lymph node of mice within 10 days. Our results demonstrate that a 15-amino acid peptide (aa 315-329) derived from the V3 loop of HIV gp120 caused a rapid induction of peptide-specific and gp160-specific CD8-positive CTLs. Lysis of targets is specific since cells preincubated with unrelated peptides are resistant to lysis as are cells of a different MHC haplotype pretreated with the cognate peptide. Pretreatment of restimulated node cells with complement plus anti-CD8 but not anti-CD4 removed the lytic activity. We also successfully induced in vivo CTL activity with unmodified synthetic peptides from the influenza and Sendai virus nucleoproteins, indicating general applicability of our method for rapid screening of CTL epitopes. Because HIV replication has been reported by several labs to occur mainly in lymph nodes of infected patients, the rapid induction of HIV-specific CTLs in proximal lymph nodes by unmodified peptides emphasizes the physiological significance of our findings toward vaccine and therapeutic approaches.
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PMID:Rapid in vivo induction of HIV-specific CD8+ cytotoxic T lymphocytes by a 15-amino acid unmodified free peptide from the immunodominant V3-loop of GP120. 131 70

T cell stimulation by the human immunodeficiency virus 1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules in a cell-free system was found to require proteolytic cleavage. This extracellular processing was mediated by peptidases present in fetal calf serum. In vitro processing of p18 resulted in a distinct reverse phase high performance liquid chromatography profile, from which a biologically active product was isolated and sequenced. This peptide processing can be specifically blocked by the angiotensin-1 converting enzyme (ACE) inhibitor captopril, and can occur by exposing p18 to purified ACE. The ability of naturally occurring extracellular proteases to convert inactive peptides to T cell antigens has important implications for understanding cytotoxic T lymphocyte responses in vivo, and for rational peptide vaccine design.
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PMID:Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules. 131 30

The bestfit computer program was used to compare the amino acid sequence of the gp160 envelope glycoprotein of an apathogenic AGM and the pathogenic SIVAGM monkey lentiviruses. It was found that the gp120 envelope glycoproteins of these viruses resembled each other in their functional domains. However, an insert of 40 amino acids was found in the gp41 envelope glycoproteins of the pathogenic SIVAGM virus in the amino acid sequence between the membrane anchoring sequence and the carboxyterminus. The insert introduced a new "RRIR" proteolytic cleavage signal into gp41. Comparing HIV-1 gp41 to that of the pathogenic SIVAGM virus revealed that the HIV-1 sequence contains an "RR" sequence that also serves as a signal for proteolytic cleavage. Comparing HIV-2 gp41 to the apathogenic and pathogenic simian immunodeficiency viruses revealed that HIV-2 gp41 lacks the above proteolytic cleavage signal. It is hypothesized that the pathogenic human and simian immunodeficiency lentiviruses can be proteolytically cleaved at the carboxyterminus of gp41, releasing two peptides: a) an "immunodeficiency" 58 amino acid peptide and b) an IL-2-like peptide. The apathogenic AGM virus and the less pathogenic HIV-2 lack one proteolytic cleavage signal in the gp41 amino acid sequence and therefore can release only the IL-2-like peptide but not the "immunodeficiency" peptide. If indeed the pathogenic SIVAGM and HIV-1 do release an "immunodeficiency" peptide, then such a peptide can be regarded as a toxin. Immunization of healthy individuals or HIV-1 patients against the toxic effect of the viral gp41 toxic peptide might prevent damage to the immune system when the virus reactivation leads to ARC and AIDS in infected individuals. Synthetic peptides modeled according to the immunodeficiency peptide (the toxin) can be used to produce anti-toxin antibodies in healthy HIV-1 infected individuals. Such anti-toxin antibodies can be used for passive immunization of AIDS patients or for active immunization of HIV-1 positive individuals prior to ARC or AIDS.
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PMID:Computer analysis of the amino acid sequences in gp41 of apathogenic African green monkey (AGM) virus, less pathogenic HIV-2 and highly pathogenic SIV and HIV-1 lentiviruses. 133 29

The role of carbohydrates in the immunogenicity of human immunodeficiency virus type 1 (HIV-1) glycoproteins (gp160 and gp120) remains poorly understood. We have analyzed the specificity and neutralizing capacity of antibodies raised against native gp160 or against gp160 deglycosylated by either endo F-N glycanase, neuraminidase, or alpha-mannosidase. Rabbits immunized with these immunogens produced antibodies that recognized recombinant gp160 (rgp160) from HIV-1 in a radioimmunoassay and in an enzyme-linked immunosorbent assay. Antibodies elicited by the different forms of deglycosylated gp160 were analyzed for their reactivity against a panel of synthetic peptides. Compared with anti-native gp160 antisera, serum reactivity to most peptides remained unchanged, or it could increase (peptide P41) or decrease. Only antibodies raised against mannosidase-treated gp160 failed to react with a synthetic peptide (peptide P29) within the V3 loop of gp120. Rabbits immunized with desialylated rgp160 generated antibodies which recognized not only rgp160 from HIV-1 but also rgp140 from HIV-2 at high titers. Although all antisera produced against glycosylated or deglycosylated rgp160 could prevent HIV-1 binding to CD4-positive cells in vitro, only antibodies raised against native or desialylated gp160 neutralized HIV-1 infectivity and inhibited syncytium formation between HIV-1-infected cells and noninfected CD4-positive cells, whereas antibodies raised against alpha-mannosidase-treated gp160 inhibited neither virus replication nor syncytium formation. These findings indicate that the carbohydrate moieties of gp160 can modulate the specificity and the protective efficiency of the antibody response to the molecule.
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PMID:Influence of carbohydrate moieties on the immunogenicity of human immunodeficiency virus type 1 recombinant gp160. 134 97

We found that naive (CD45RA+) CD4 T cells have a lower capacity of adhesion to Epstein-Barr virus (EBV) immortalized B cells than memory (CD45RO+) CD4 T cells, as judged by conjugate formation. This would appear to be due to differences in the expression of adhesion molecules [lymphocyte function-associated antigen (LFA)-1, CD2]. However, kinetic studies showed that the degree of adhesion of naive T cells to B cells was stable over 60 min while that of memory T cells, like that of unseparated CD4 T cells, was characterized by a rapid formation and rapid dissociation of conjugates. This could be explained by a difference in the sensitivity of naive and memory CD4 T cells to down-regulation of antigen-independent adhesion by CD4-MHC class II interaction. Indeed, memory T cells also adhered stably to MHC class II(-) B cells. The adhesion of memory T cells, but not naive T cells, to MHC class II(+) B cells was sensitive to inhibition by OKT4a an anti-CD4 antibody, human immunodeficiency (HIV) gp160 (env) protein and a 12-mer peptide encompassing the 35-46 sequence of the HLA, DR beta 1 domain and previously shown to inhibit activation of HLA class II-restricted CD4 T cell responses. Since MHC class II expression did not influence the degree of conjugate formation by naive or memory CD4 T cells with B cells, CD4-MHC class II interaction does not appear to be involved in binding itself, but may down-regulate the adhesion of memory but not naive CD4 T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antigen-independent adhesion of CD45RA (naive) and CD45RO (memory) CD4 T cells to B cells. 135 61

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) gp160 recombinant vaccinia virus (HIVAC-1e) vaccine was evaluated in vaccinia-naive, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 36) were randomized to receive HIVAC-1e or control vaccinia virus at two dosages by bifurcated needle puncture at 0 and 2 months; 12 HIVAC-1e and 6 control vaccinia virus recipients received either 10(6) or 10(7) pfu/mL at each inoculation. There was no significant difference in lesion size, level of viral replication, or systemic symptoms after vaccination with HIVAC-1e or control vaccinia virus. Of 22 HIVAC-1e recipients with lesion formation, 16 developed low-titer gp160-specific antibody responses detectable by Western blot. The peak response occurred between days 70 and 120 and was still detectable at day 365 in 9 of 18 vaccinees. gp160-specific lymphoproliferative responses were detected in 5 of 10 vaccinees. Vaccination with HIVAC-1e was safe in vaccinia-naive, healthy adults and could induce both humoral and cell-mediated gp160-specific immune responses.
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PMID:Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. The AIDS Vaccine Clinical Trials Network. 135 2


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