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

T helper cell antigenic and immunogenic determinants of the nef protein were investigated in the rat and chimpanzee models using recombinant nef protein and five synthetic peptides selected according to their amphipathic and alpha-helicity properties. The nef protein was shown to be immunogenic with both Freund's or aluminium hydroxide adjuvants. After immunization with the nef protein the 45-69 peptide was the most antigenic in rat and monkey models. In contrast, the 98-112 peptide, that required a carrier protein to induce in vitro rat T cell recall proliferation, was able to restimulate monkey T cells in the absence of a carrier. The amino acid sequence carrying the antigenic activity of the 45-69 peptide was further investigated by synthesizing short peptides overlapping this region. The antigenic sequence was precisely located in the middle of the peptide (region 50-59). This sequence was antigenic only when N alpha-acetylated. Circular dichroism analysis of the 45-69 peptide and the in vitro activity of the N-terminus group indicate in this case the involvement of the alpha-helical propensity for antigen presentation. However, the shorter sequence 50-64, able to induce a T cell reactivity, was determined as a beta-pleated sheet structure in aqueous solution. The 45-69 peptide was not only antigenic but also immunogenic and behaved in vivo as a functional T helper cell epitope. Indeed, the priming with the peptide or the transfer of peptide specific T cells to a naive recipient, followed by immunization with the nef protein, enhanced the subsequent antibody response to the nef protein. Together, these data indicate that the 45-69 peptide appears as a candidate for the in vivo elicitation of T cell immunity to the HIV-1 nef regulatory protein.
Mol Immunol 1992 Apr
PMID:T helper cell epitopes of the human immunodeficiency virus (HIV-1) nef protein in rats and chimpanzees. 137 67

The antigenicity of HIV-gag p17 and p25 proteins was analyzed using a panel of 52 monoclonal antibodies (mAb) derived from 17 independent fusion experiment protocols performed in 12 different laboratories. These mAb were tested for their capacity to bind peptides corresponding to sequences of HIV1-BRU-gag p17 and p25. Thirty-five overlapping peptides (P1 to P35) totally covering the p17 and p25 proteins were used. This study allowed us to identify four immunodominant regions inducing B cell response, two on p17 corresponding to P2 and P13 (amino acids 11-25 and 121-132, respectively) and two on p25 corresponding to P21 and P28-P29-P30 (a.a. 201-218 and 285-320 respectively). According to secondary structure predictions, peptides P2 and P21 contained hydrophilic alpha helix folded regions whereas P13 sequence presented a beta turn propensity. These regions and the P28-30 region were also predicted to be easily accessible to mAb. Several other p25-derived peptides: P15 (a.a. 142-156), P16 (a.a. 148-162), P19 (a.a. 176-192), P22 (a.a. 219-233) and P23 (a.a. 233-253) were recognized by mAb. No p17-derived peptide other than P2, P13 and P12 (a.a. 111-123) was found to react with mAb. Cross-blocking studies between mAb, suggested the existence of more than four distinct epitopic areas on p17 and eight on p25.
Mol Immunol 1992 Jun
PMID:Clonal analysis of murine B cell response to the human immunodeficiency virus type 1 (HIV1)-gag p17 and p25 antigens. 137 12

Primer tRNA regions involved in the interactions between human immunodeficiency virus reverse transcriptase (HIV RT) and tRNA(Lys) were studied by digestion of primer with pancreatic ribonuclease in the presence or absence of HIV RT. The acceptor stem of tRNA(Lys) is not noticeably protected against nuclease action in the presence of HIV RT, while this enzyme clearly protects part of the anticodon and dihydrouridine loops of tRNA(Lys). The acceptor stem of primer tRNA was digested by RNase A only in the presence of the retroviral enzyme, suggesting a partial destabilization of this region by the HIV RT. Synthetic oligoribonucleotides, corresponding to the anticodon and the dihydrouridine loops, inhibited strongly reverse transcription, confirming the strong interaction of these tRNA regions with the enzyme.
J Mol Biol 1992 Jul 05
PMID:Preferential interaction of human immunodeficiency virus reverse transcriptase with two regions of primer tRNA(Lys) as evidenced by footprinting studies and inhibition with synthetic oligoribonucleotides. 137 51

In this report, we assess the humoral immune response in inbred strains of mice immunized with baculovirus-derived recombinant HIV-1 gp160 (rgp160). Six inbred strains of mice were each immunized with two different concns (5 and 50 micrograms) of rgp160, and the antibody response to rgp160 and synthetic peptides which define distinct gp160 epitopes was examined. Within a given inbred strain of mice, no significant difference in antibody titers to gp160 was observed in those groups receiving either 5 or 50 micrograms of rgp160 per injection. Following three immunizations with rgp160, differences in anti-gp160 titers were observed among the various inbred strains; however, these differences became less apparent after additional injections with rgp160. In addition, each mouse strain exhibited a unique reactivity pattern to seven gp160 epitopes defined by synthetic peptides. Multiple injections with rpg160 were required to induce responses to certain gp160 epitopes. The observed differences in the fine specificity of the humoral immune response to distinct gp160 epitopes among the six inbred strains suggest a genetic basis for regulating the antibody response to these epitopes. This apparent regulation can be overcome by multiple injections with rgp160.
Mol Immunol
PMID:Fine specificity of the murine antibody response to HIV-1 gp160 determined by synthetic peptides which define selected epitopes. 137 36

To understand better the specificity of peptide binding by MHC class I molecules, we have evaluated the capacity of a panel of unrelated peptides to compete for the presentation of viral peptides presented by HLA-A3 and HLA-B27. The HIV-Nef7F peptide (74-82) was presented by HLA-A3 to Nef-specific HLA-A3-restricted CTL lines, and the influenza nucleoprotein peptide NP(380-393) was presented by HLA-B27 to NP(380-393)-specific HLA-B27-restricted CTL lines. In addition, we have extended studies from our group that have evaluated the capacity of a similar panel of peptides to inhibit presentation of an influenza nucleoprotein peptide NP (335-349) by HLA-B37 and a matrix peptide, M1 (57-68), by HLA-A2 to the appropriate peptide-specific CTL lines. Out of 41 peptides tested, only five bound to more than one of the MHC molecules analyzed. Pairwise comparisons of the peptide binding specificities among these four different class I molecules revealed no common competitor peptides in four of the six possible comparisons. Thus, each class I molecule appears to have a functionally distinct peptide binding site, as reflected by the ability to bind largely non-overlapping sets of peptides.
Mol Immunol 1992 Sep
PMID:The peptide binding specificity of HLA class I molecules is largely allele-specific and non-overlapping. 137 81

An efficient strategy has been devised for the construction of diverse peptide libraries in bacteriophage vectors. This strategy was used to generate a library of 4 x 10(8) random decapeptide inserts in the pIII protein of bacteriophage fd. A novel method for evaluating the genetic diversity of bacteriophage libraries based on colony hybridization with partially degenerate oligonucleotides has been developed. The decapeptide library was affinity-selected with a previously characterized monoclonal antibody specific for the V3 loop of the gp120 protein of HIV-1. Immunological screening, an efficient technique for the rapid identification of putative binding bacteriophage, is described. Hexapeptide sequences similar to those obtained from affinity selection of a hexapeptide bacteriophage library were obtained from the decapeptide library in all five frames. Immunological screening of 20,000 clones from the two libraries after two rounds of affinity selection rapidly identified antibody-binding sequences; 93% and 86% of the sequences obtained from the hexapeptide and decapeptide libraries, respectively, had IC50 values < or = 10 mM as free peptides.
J Mol Biol 1992 Oct 05
PMID:Simplified methods for construction, assessment and rapid screening of peptide libraries in bacteriophage. 140 85

Five strains of human immunodeficiency virus type 1 (HIV-1) were isolated from five Japanese hemophilia patients. Two isolates, HIV-1[GUN-1] and HIV-1[GUN-2], were from brother patients with hemophilia B and the other three isolates, HIV-1[GUN-3], HIV-1[GUN-4], and HIV-1[GUN-5], were from hemophilia A patients. Another HIV-1 strain, HIV-1[GUN-6], was isolated from a Canadian male homosexual with AIDS. The restriction endonuclease cleavage maps of the proviral genomes of these six HIV-1 strains revealed that they were apparently different from each other. The phylogenetic trees constructed using restriction maps and nucleotide sequences were quite similar, indicating that phylogenetic analyses of Japanese HIV-1 isolates can be done using restriction maps of the proviruses. Phylogenetic analyses showed that they were more closely related to HIV-1s which had been reported to be isolated from homosexual patients in the United States than those isolated from African patients. In particular, GUN-1 and GUN-2 isolates were on the branch of a San Francisco isolate, ARV2, while GUN-5 and GUN-6 isolates were on the branch of HTLV-IIIB-related isolates.
J Mol Evol 1992 Oct
PMID:Six strains of human immunodeficiency virus type 1 isolated in Japan and their molecular phylogeny. 140 18

A number of nucleoside 5'-phosphonates and nucleoside 5'-methylphosphonates were synthesised, to study their ability to inhibit reproduction of HIV-1. Three compounds, 5'-hydrogen phosphonates of 3'-azido-2',3'-dideoxythymidine (AZT-HP, IVc), 3'-fluoro-2',3'-dideoxythymidine (FLT-HP, IVa) and 2',3'-dideoxyadenosine (ddA-HP, I), exhibit potent anti-HIV-1 activity with selectivity indices similar to or better of those of their parent nucleosides.
Mol Biol (Mosk)
PMID:[New 5'-phosphonates, modified through the nucleoside sugar residue, as inhibitors of HIV replication]. 140 17

Specificity of anti-p25 antibodies produced against either whole Human Immunodeficiency Virus type 1 (HIV-1) particles in humans and chimpanzees, or against soluble forms of the protein in chimpanzees and rabbits was analyzed by ELISA using a panel of 37 long (> or = 30 residues) or shorter (9-21 residues) overlapping peptides covering the entire p25 sequence. Antibodies elicited by intact virions presented similar reactivity patterns in HIV-1-infected humans and in HIV-1-infected or immunized chimpanzees and recognized only a limited region mostly the C-terminus of the molecule. Moreover, 8 of the human sera (36%), which nonetheless reacted with high titers and avidity with native p25, did not bind to any long or short peptide. These results suggest that the majority of antibodies elicited by viral particles are presumably directed to conformational epitopes. In contrast, antibodies raised against soluble forms of p25 could react against all long peptides but one (residues 211-245) and against some short peptides, indicating that most of p25 sequence may be immunogenic under these conditions. These results suggest that the reactivity spectrum of anti p25 antibodies is rather different if they are produced against intact HIV-1 particles or the soluble protein. They also indicate that it may be possible to manipulate the specificity of the humoral immune response by using either intact virions or purified proteins.
Mol Immunol 1992 Nov
PMID:Specificity of anti-P25 antibodies produced against whole HIV-1 particles or soluble forms of the protein. 140 19

A CD4 peptide of amino acid residues 68-130 [CD4(68-130)], which had the capacities to inhibit HIV-1 replication and HIV-1-induced syncytium formation, was used as an immunogen for the preparation of mAb. The mAbs prepared were classified into at least five types (I-V) in terms of their recognition sites by ELISA using various kinds of smaller CD4 peptides. Among them, the type I mAb no. 35 recognizing amino acid residues 72-84, which lies just before the region corresponding to an immunoglobulin third complementarity-determining region (CDR3), showed the strongest effects in reducing both HIV-1 infection and HIV-1-induced syncytium formation, although a large amount of no. 35 mAb was necessary to reduce such HIV-1 activities compared with those of anti-Leu-3a and OKT4A mAbs which recognize CD4 epitopes near a portion corresponding to an immunoglobulin CDR2. Western blot analysis showed that the reactivities of CD4 molecule in CD4-positive cells or sCD4 molecule with types I-V mAbs were stronger than that with anti-Leu-3a mAb. Flow cytometry showed that no. 35 mAb was faintly reactive with native CD4 molecule on cell surface at the concn showing the inhibitory effects on HIV-1 infection and syncytium formation. In addition, a smaller peptide CD4(66-92), one of the good epitope peptides for no. 35 mAb, also showed strong inhibitory effect on HIV-1 infection as well as a weaker inhibitory effect on syncytium formation. These results suggest that, in addition to the CD4 CDR2-related region, the pre-CDR3-related region is also involved in the early events of the interactions between the host cell and HIV-1.
Mol Immunol 1992 Nov
PMID:Monoclonal antibodies to a CD4 peptide derivative which includes the region corresponding to an immunoglobulin CDR3: evidence of the involvement of pre-CDR3-related region in HIV-1 and host cell interaction. 140 23


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