Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-three strains of Cryptococcus neoformans were isolated from clinical specimens, including specimens from AIDS patients in Brazil, and were classified into two serotypes; we detected 31 and 2 strains of serotypes A and B, respectively. Random amplified polymorphic DNA (RAPD) fingerprint pattern analyses of these strains of serotypes A and B showed that the patterns were similar for strains of each serotype when three 10-mer primers were used as the RAPD primers. Comparative studies of the fingerprint patterns of the study isolates with those of the reference strains also showed that the RAPD patterns for strains of each serotype were related and that most of the fingerprint bands existed commonly for all strains of each serotype tested. The common RAPD bands (an approximately 700-bp band for serotype A and an approximately 450-bp band for serotype B) were extracted and the DNA sequences were determined. Using this information, we prepared two and one PCR primer pairs which were expected to be specific for C. neoformans serotypes A and B, respectively. Use of each PCR primer combination thus prepared for serotype A or B was 100% successful in identifying the respective C. neoformans serotypes, including the 33 clinical isolates tested in the present study. Among these combinations, one for serotype A was found to amplify DNA from C. neoformans serotype B as well as serotype A. Serotype B-specific PCR primer pairs amplified DNA from not only serotype B strains but also from serotype C strains. The usefulness of other serotype-specific PCR primers for clinical C. neoformans isolates is discussed.
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PMID:New PCR primer pairs specific for Cryptococcus neoformans serotype A or B prepared on the basis of random amplified polymorphic DNA fingerprint pattern analyses. 988 10

In the present study a novel Ab-avidin fusion protein has been constructed to deliver biotinylated compounds across the blood brain barrier. This fusion molecule consists of an Ab specific for the transferrin receptor genetically fused to avidin. The Ab-avidin fusion protein (anti-TfR IgG3-CH3-Av) expressed in murine myeloma cells was correctly assembled and secreted and showed both Ab- and avidin-related activities. In animal models, it showed much longer serum half-life than the chemical conjugate between OX-26 and avidin. Most importantly, this fusion protein demonstrated superior [3H]biotin uptake into brain parenchyma in comparison with the chemical conjugate. We also delivered a biotinylated 18-mer antisense peptide-nucleic acid specific for the rev gene of HIV-1 to the brain. Brain uptake of the HIV antisense drug was increased at least 15-fold when it was bound to the anti-TfR IgG3-CH3-Av, suggesting its potential use in neurologic AIDS. This novel Ab fusion protein should have general utility as a universal vehicle to effectively deliver biotinylated compounds across the blood-brain barrier for diagnosis and/or therapy of a broad range of CNS disorders such as infectious diseases, brain tumors as well as Parkinson's and Huntington's diseases.
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PMID:An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting: initial applications in anti-HIV antisense drug delivery to the brain. 1051 Mar 83

Stromal cell-derived factor 1 (SDF-1), a member of the CXC chemokine family, is the only chemokine to bind to the receptor CXCR4. This receptor is also a co-receptor for syncytia-inducing forms of HIV in CD4(+) cells. In addition, SDF-1 is responsible for attracting mature lymphocytes to the bone marrow and can therefore contribute to host versus graft rejection in bone marrow transplantation. Clearly, by manipulating SDF-1 activity, we could find a possible anti-viral AIDS treatment and aid in bone marrow transplantation. SDF-1 binds to CXCR4 primarily via the N terminus, which appears flexible in the recently determined three-dimensional structure of SDF-1. Strikingly, short N-terminal SDF-1 peptides have been shown to have significant SDF-1 activity. By using NMR, we have determined the major conformation of the N terminus of SDF-1 in a 17-mer (residues 1-17 of SDF-1) and a 9-mer dimer (residues 1-9 of SDF-1 linked by a disulfide bond at residue 9). Residues 5-8 and 11-14 form similar structures that can be characterized as a beta-turn of the beta-alphaR type. These structural motifs are likely to be interconverting with other states, but the major conformation may be important for recognition in receptor binding. These results suggest for the first time that there may be a link between structuring of short N-terminal chemokine peptides and their ability to activate their receptor. These studies will act as a starting point for synthesizing non-peptide analogs that act as CXCR4 antagonists.
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PMID:NMR studies of active N-terminal peptides of stromal cell-derived factor-1. Structural basis for receptor binding. 1084 82

Fusion between the envelope of HIV and the plasma membrane of target cells is mediated by gp41, the envelope glycoprotein of HIV. Peptides derived from the membrane-proximal helical motif of the extracellular domain of gp41 effectively inhibit the infection of HIV, and their inhibitory activities are known to be correlated with the helical propensity of the peptides. We have designed small peptides that can form a stable alpha helix and thereby inhibit gp120/41-mediated cell fusion. A 19-mer peptide from the membrane-proximal helical motif of gp41 had no secondary structure in solution, and failed to block gp41-mediated cell fusion. When amino acids with low helical propensity were substituted, and helix-capping sequences were introduced at both ends of the peptides, the modified peptides formed a stable helical structure. They also bound to the coiled-coil motif of gp41 presented at the C terminus of thioredoxin and blocked the cell fusion mediated by gp120/41. These results implied that such modification was enough to change a short peptide derived from gp41 into a potent inhibitor against the infection of HIV.
AIDS Res Hum Retroviruses 2000 Nov 20
PMID:Design of a peptide inhibitor that blocks the cell fusion mediated by glycoprotein 41 of human immunodeficiency virus type 1. 1111 65

We have identified a peptide region on CD18 molecule (the beta subunit of the LFA-1 molecule) involved in syncytia formation of HIV-1-infected lymphocytes. Several phage clones mimicking an epitope of the CD18 cell-surface determinant were isolated from two 9-mer random peptide phage-displayed libraries via their binding to the CD18-specific monoclonal antibody (mAb) MHM23, which in in vitro assay inhibits syncytia formation in HIV-1-infected cells. The peptide sequences displayed on phages that blocked immunolabeling of this mAb on LFA-1-expressing cells were used to identify the epitope recognized by mAb MHM23 by sequence comparison. On the basis of this analysis, two peptides which inhibited syncytia formation in HIV-1-infected cells in vitro were synthesized, thus confirming that they mimic a CD18 domain that is involved in this phenomenon. The results here presented highlight the potential of phage-display technology for the study of biological processes at the basis of virus infection, but also suggest new approaches for the therapy of AIDS.
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PMID:Identification of a LFA-1 region involved in the HIV-1-induced syncytia formation through phage-display technology. 1116 38

Only limited cytotoxic T lymphocyte (CTL) epitope mapping has been done in nonsubtype B HIV-infected persons. We used molecular immunogenetic tools to determine HIV-specific CTL responses in HIV-1 Env subtype E-infected female sex workers (FSWs) from northern Thailand, where more than 50% of the population is HLA-A11 positive. EpiMatrix, a computer-based T cell epitope prediction algorithm, and a manual editing approach were used to predict 77 possible HLA-A11 CTL epitopes in HIV-1, some of which were conserved between subtypes B and E. MHC binding of these peptides was determined in an HLA-A11 stabilization assay, and binding peptides were tested for CTL recognition in eight HLA-A11-positive FSWs. Subtype E versions of known HLA-A2 subtype B HIV epitopes were also tested in four HLA-A2 positive FSWs. CTL responses were detected in all HLA-A11-positive and in three of four HLA-A2-positive persons. Among the 12 FSWs responses to peptides were found to Pol in 9 (75%), Env in 7 (58%), Nef in 5 (42%), and Gag in 5 (42%), and to conserved epitopes in 8 (67%). To identify HLA-A11 CTL epitopes in the absence of prediction tools, it would have been necessary to test almost 3000 10-mer peptides. EpiMatrix and manual predictions reduced this number to 77, of which 26 were MHC binding and 12 were CTL epitopes. Six of these HLA-A11 CTL epitopes have not been previously reported and are located in RT, gp120, and gp41. This report of CTL responses in subtype E-infected individuals defines epitopes that may be useful in HIV pathogenesis or vaccine studies.
AIDS Res Hum Retroviruses 2001 May 20
PMID:An HLA-directed molecular and bioinformatics approach identifies new HLA-A11 HIV-1 subtype E cytotoxic T lymphocyte epitopes in HIV-1-infected Thais. 1142 11

RNase I and RNase T1 can be used to obtain high-quality footprinting information for paromomycin binding to a 176-mer RNA from the packaging region of HIV-1 (LAI). Controls and scanning procedures are necessary for quantitation of autoradiographic data, so that footprinting plots showing cutting behavior as a function of drug concentration can be used to identify binding sites and regions of altered structure on the 176-mer. From the RNase I footprinting results the primary paromomycin binding sites on the 176-mer are on the main stem and on the stem of SL1, but noncontiguous sequences may be involved in the same binding event. Strong enhancements in cleavage with added drug are also observed, indicating drug-induced structural changes. Drug binding may cause linker regions between stem-loops of the 176-mer to change structure, possibly providing a site or sites for additional drug binding. Because drug binding changes the structure of the packaging region, which may alter its function, paromomycin analogs with enhanced specificity for HIV psi RNA have potential as a new class of agent for treating AIDS.
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PMID:Drug-RNA footprinting. 1149 62

Fomivirsen (ISIS-2922, Vitravene) is an antisense 21 mer phosphorothioate oligonucleotide with sequence complementarity to the coding region of the major immediate-early gene of human cytomegalovirus (CMV). Developed by Isis Pharmaceuticals Inc, fomivirsen is the first antisense oligonucleotide to receive approval for licensing and is marketed by Novartis' CIBA Vision. Fomivirsen is administered by intravitreal injection to AIDS patients for the treatment of CMV-induced retinitis. In August 1998, the FDA approved the marketing of Vitravene for the local treatment of CMV retinitis [296420], [296780], and both European and Brazilian registration approval followed in the summer of 1999 [335238].
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PMID:Technology evaluation: fomivirsen, Isis Pharmaceuticals Inc/CIBA vision. 1149 53

The chemokine receptors CXCR4 and CCR5 are used as co-receptors by the T cell-tropic (X4) and macrophage-tropic (R5) HIV-1 strains, respectively, for entering their host cells. Viral entry can be inhibited by the natural ligands for CXCR4, the CXC chemokine SDF-1 and CCR5, the CC chemokines RANTES, MIP-1alpha and MIP-1beta. Several peptidic compounds, T22 (an 18-mer), T134 (a 14-mer), ALX40-4C (a 9-mer) and CGP 64222 (also a 9-mer), have been identified as CXCR4 antagonists and show anti-HIV activity. Also, the HIV-1 tat protein has been described as a 'natural' CXCR4 antagonist with anti-HIV-1 activity. The most potent and specific CXCR4 antagonists are the bicyclam derivatives, which also potently block X4 HIV replication. AMD3100 has proved to be a highly specific CXCR4 antagonist, which consistently blocks the outgrowth of all X4 HIV and dual-tropic (R5/X4) variants that use CXCR4 for entering the cells (cell lines, CXCR4-transfected cell lines, lymphocytes or monocytes/ macrophages). From the bicyclam analogues, AMD3100 was selected as the clinical drug candidate, which, after initial Phase I (safety) studies, has proceeded to Phase II (efficacy) trials. The first non-peptidic compound that interacts with CCR5, and not with CXCR4, is a quaternary ammonium derivative, called TAK-779, which also has potent but variable anti-HIV activity. We believe that HIV entry/fusion inhibitors will become important new antiviral agents to combat AIDS. However, like the current clinically approved agents, they will need to be used in combinations consisting of antivirals that target other aspects of the HIV replication cycle, such as reverse transcriptase and protease, to obtain optimum therapeutic effects.
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PMID:Inhibition of HIV infection by CXCR4 and CCR5 chemokine receptor antagonists. 1159 85

The gag p17 matrix sequences of human immunodeficiency virus type 1 (HIV-1) were analyzed from three nontransmitting mothers (mothers who failed to transmit HIV-1 to their infants in the absence of antiretroviral therapy), including multiple deliveries in the case of mother 3. There was a low degree of heterogeneity of gag p17 matrix sequences in nontransmitting mothers compared with our previously analyzed mother-infant pairs' sequences. Whereas most of the functional domains essential for p17 matrix function were generally conserved, the polymerization site was less conserved. Several amino acid motifs, including KIEEEQN (positions 103-109) at the major antibody-binding site, were variable and the C-terminal 6-mer QVSQNY, a lysine or glutamine at position 15, an alanine at position 54, a lysine at position 76, a valine at position 104, and an aspartic acid at positions 102 and 121 were conserved in nontransmitting mothers' sequences compared with transmitting mothers' sequences. Phylogenetic analyses of 82 p17 matrix sequences revealed distinct clusters for each nontransmitting mother. Some of these motifs in gag p17 matrix sequences that are present in nontransmitting mothers and absent in transmitting mothers could be used as new targets for the development of preventive strategies for perinatal transmission.
AIDS Res Hum Retroviruses 2001 Nov 20
PMID:Genetic characterization of HIV type 1 gag p17 matrix genes in isolates from infected mothers lacking perinatal transmission. 1177 56


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