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

Serologic V3 loop peptide-binding assays have been used to predict divergent human immunodeficiency virus type 1 (HIV-1) strains from the Commonwealth of Independent States (former Soviet Union) that have been subsequently confirmed by sequencing of the V3 region. Initial screening was done by MN V3 peptide binding; 12 parenterally infected HIV-1-positive subjects from Elista and Rostov (group 1) with low-titer MN binding and 6 heterosexually infected HIV-1-positive adults from Byelorussia (group 2) with high-titer MN binding were selected. A consensus sequence from the Elista and Rostov areas was generated; a corresponding 14-mer peptide was synthesized and used in an indirect ELISA to screen sera from 392 individuals from diverse geographic areas. Reactivity to the consensus peptide was 82% in subjects from the homologous areas and 11%-38% in other areas. Antibody binding to a panel of synthetic V3 peptides may be used to predict the presence of diverse strains of HIV-1 within virally heterogenous populations.
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PMID:Identification of human immunodeficiency virus type 1 subtypes and their distribution in the Commonwealth of Independent States (Former Soviet Union) by serologic V3 peptide-binding assays and V3 sequence analysis. 833 67

The introduction of isotopically enriched nucleotides into NMR quantities of a synthetic 29-mer RNA derived from the HIV-1 TAR element is described. RNA enriched in 13C and/or 15N is produced by a procedure which involves isolation of whole cellular RNA from Escherichia coli, nucleolysis, separation of mononucleotides, chemical or enzymatic pyrophosphorylation, and in vitro transcription by T7 RNA polymerase. Spectral characteristics of each residue type are examined in isolation. 13C chemical shifts provide an alternative method to determine ribose puckers for larger RNAs. Nonprotonated sites such as purine N7 groups can now be monitored through the use of multiple-bond 1H-15N coupling. When applied conservatively, coordinate analysis of chemical shift values should prove valuable for NMR studies of RNA structure and recognition. 1H, 13C, and 15N chemical shift data suggest that TAR residue A35 has an unusual local environment, consistent with extrusion of its base from the terminal loop.
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PMID:Selective isotopic enrichment of synthetic RNA: application to the HIV-1 TAR element. 842 47

12-Mer analogues, representative of seven different classes of structurally modified oligonucleotides and complementary to the same target, have been compared for their binding affinity for both single-stranded DNA and RNA, resistance to hydrolysis by nucleases in culture medium (RPMI 1640 + 10% inactivated fetal calf serum), and inhibition of HIV-1 replication in de novo infected MT4 T lymphocytes. The viral target was the splice acceptor site of the premessenger coding for the regulatory protein tat. The oligo(2'-O-alkyl)ribonucleotides (beta-2'O-allyl-RNA and beta-2'OMe-RNA) were shown to form the most stable hybrids with complementary RNA strands whereas the alpha-anomeric oligodeoxynucleoside phosphorothioate analogue displayed the highest stability in the culture medium. All the modified oligonucleotides examined in the present study exhibited a sequence-nonspecific inhibitory effect on HIV-1 replication, the phosphorothioate analogues being the most active ones (ED50 < 1 microM).
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PMID:Comparative evaluation of seven oligonucleotide analogues as potential antisense agents. 842 98

Hairpin ribozymes derived from (-)sTRSV RNA exhibit substantial cleavage activity when wobble GU base pairs are introduced in place of the AU pairs normally involved in helices I and II between substrate and ribozyme. This finding prompted us to synthesize by in vitro transcription a new hairpin ribozyme, active against a 14-mer substrate derived from a conserved HIV sequence. Interactions of the canonical and anti-HIV hairpin ribozymes with non cleavable DNA substrate analogues containing the photoaffinity probe deoxy-4-thiouridine (ds4U) at a single site were investigated. Upon near-UV light irradiation (365 nm), all these substrate analogues were covalently attached to ribozyme via single or multiple crosslinks. In contrast, no crosslinks were detected using either a DNA substrate analogue lacking ds4U or a ds4U containing oligomer unrelated to the substrate sequence. As expected, if the dissociation constant is in the range of 5-15 microM, the yield of crosslinked ribozyme increased markedly with increasing the substrate analogue concentration. The ribozyme residues involved in the crosslinks were determined by RNA sequencing. The pattern of crosslinks obtained with the two ribozyme systems provides additional evidence in support of the consensus secondary structure proposed for the hairpin domain. Minor alternative conformations were detected in the case of the (-)sTRSV system.
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PMID:Folding of DNA substrate-hairpin ribozyme domains: use of deoxy 4-thiouridine as an intrinsic photolabel. 844 28

Although having variability in primary sequence, the v3 loop of gp120 in pathogenic strains of human immunodeficiency virus type-1 (HIV-1) is positively charged and known to interact with sulfated polysaccharides. Because the interaction of sulfated polysaccharides with the v3 loop inhibits HIV infection in vitro, we investigated the interaction of the v3 loop with phosphodiester (PO) and phosphorothioate (PS) oligodeoxynucleotides (oligos). In a solid-phase ELISA assay, a PS 28-mer homopolymer of cytidine, SdC28, blocked the binding of the v3 loop-specific monoclonal antibody (mAb) 9284 to rgp120 more potently than did dextran sulfate. In addition, like dextran sulfate, SdC28 appeared to bind specifically to the v3 loop, because neither compound inhibited the binding of other anti-gp120 mAbs. In contrast to PS oligos, PO oligos did not inhibit mAb 9284 binding. The length dependence of the interaction of PS oligos with the v3 loop was studied by using a series of PS oligos. A discrete loss of inhibiting activity occurred as a function of decreasing PS oligo length, which was most marked between PS oligos of 18-mer and 12-mer in length. We further probed the chemical nature of the interaction of oligos with gp120 by measuring the gp120 binding affinities of PS and PO oligos of various lengths. We employed a 5'-32P-labeled alkylating oligo, ClRNH32P-OdT15, and determined that the Km of gp120 binding is 4 microM. We also determined values of competition constant (Kc) for PS competitors of ClRNH32P-OdT15 binding. The binding constant (= 1/Kc) for PS oligos showed a discrete increase in gp120 binding for PS oligos > 12- to 18-mer in length, with no further increment beyond an 18-mer. Given the important role of the v3 loop in HIV-1 pathogenicity, these data suggest that therapeutic trials of PS oligos should be considered.
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PMID:Phosphorothioate oligodeoxynucleotides bind to the third variable loop domain (v3) of human immunodeficiency virus type 1 gp120. 849 4

Mice developed massive splenomegaly and polyclonal hypergammaglobulinemia within 2 days after intravenous injection of a phosphorothioate oligomer that is antisense to a portion of the rev region of the HIV-1 genome. Histologic examination of spleens from injected animals showed marked expansion of a uniform-appearing population of small lymphocytes and many mitoses. Spleen mononuclear cells (SMNCs) from injected animals showed approximately a 10-fold-increased uptake of [3H]thymidine and production of IgM and IgG. Flow cytometry analysis indicated that the responding cells were predominantly B-lymphocytes. The anti-rev oligomer also was mitogenic in vitro and stimulated immunoglobulin production by normal mouse SMNCs and human peripheral blood mononuclear cells. Similar immunologic effects were observed with an anti-rev 21-mer phosphorothioate, truncated at the 3' end, but not with a 20-mer human p53 antisense phosphorothioate or a 28-mer anti-rev phosphodiester. These observations are consistent with the possibility that DNA sequences homologous to the rev gene participate in the regulation of mammalian lymphocyte activation, proliferation and maturation.
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PMID:Immune stimulation by an antisense oligomer complementary to the rev gene of HIV-1. 851 86

A COS-like monkey kidney cell line stably transfected with the plasmids pCMVgagpol-rre-r with the gag and pol genes, and pCMV rev with the rev gene of HIV-1 derived from the cDNA clone BH10, was used as a model for assessing the effectiveness of antisense (AS) constructs, A 20-mer oligodeoxyribonucleotide (oligo) phosphorothioate sequence (5'-CCG CCC CTC GCC TCT TGC CG) complementary to a portion of the 5'-long terminal repeat (5'-LTR) of the HIV-1 genome was tested for its inhibitory effects on the biologically important processes of HIV-1 replication and proliferation. We observed a concentration-dependent inhibition of HIV protein synthesis. Desitometric analysis of data from Western blot analysis showed sequence-specific and concentration-dependent oligo inhibition of p24 viral core antigen formation in the low-microM range. When lipofectin was used as a delivery vehicle, a markedly increased potentiation of the AS activity of the sequence was observed at a lower concentration (0.1 microM), following a 24-h preincubation. The AS construct specifically inhibited intracellular p24 production in chronically HIV-1-infected cells of lymphoid origin (H9/IIIB cells) by 95%, resulting in a 15-fold inhibitory effect relative to a similar sequence thiolated at only seven single-base positions. A concentration-dependent attenuation in the reverse transcriptase activity and a reduction in viral p24 level was observed in the culture supernatant of AS-pretreated HIV-1-infected phytohemagglutinin A-stimulated human cord blood mononuclear cells. Incubation of a HIV-1-infected lymphoid cell line with AS sequence resulted in a marked reduction in syncytium formation, and therefore protected cells from the cytopathic effects of the virus. Furthermore, the AS oligo did not appear to be cytotoxic in cell growth rate and colony-forming ability assays. The AS oligo described in this report is a useful new tool for the molecular analysis of HIV-1 gene expression and proliferation, and may have potential as a therapeutic agent.
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PMID:Antiviral activity and protection of cells against human immunodeficiency virus type-1 using an antisense oligodeoxyribonucleotide phosphorothioate complementary to the 5'-LTR region of the viral genome. 854 66

In cell-mediated immunity T cells recognize peptide fragments of the antigenic protein in association with major histocompatibility complex (MHC) proteins. Synthetic 9- to 16-mer peptides have been widely used to identify the region(s) of a protein that act as T cell epitope. Here, we report antigenic peptides identified on HIV-1 regulatory protein Rev. Four synthetic peptides (amino acids 9-23, 25-39, 33-48, and 41-56) were first shown to stimulate T helper (Th) cell proliferation in peripheral blood lymphocytes (PBLs) derived from HIV-seropositive (HIV+) individuals. The same peptides induced cytotoxic T lymphocyte (CTL) activities toward the autologous target cells incubated with the peptides. Both responses were specific to the HIV infection as HIV-seronegative (HIV-) control individuals showed no significant proliferative or cytotoxic activity. The proliferating cells were CD4+ T cells, and CTL activity was mediated by CD8+ human leukocyte antigen (HLA)-restricted T cells. The identification of peptides containing epitopes that can induce both Th and CTL responses to regulatory proteins of HIV-1 in infected individuals might be important for vaccine development against AIDS. Since early regulatory proteins of HIV are expressed by the infected cells before the initiation of the synthesis of structural proteins, a CTL response against these proteins could destroy the infected cells before the release of infectious virions.
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PMID:Helper and cytotoxic T cell responses of HIV type 1-infected individuals to synthetic peptides of HIV type 1 Rev. 857 90

A 15-mer C-5 propyne modified phosphorothioate oligodeoxynucleotide antisense to rev was approximately 5-fold more effective in providing viral inhibition compared to a 28-mer unmodified phosphorothioate oligodeoxynucleotide targeted to the same sequence and previously shown to inhibit HIV-1 in a sequence-dependent manner. The antiviral effect was obtained by lipofection or simple addition of 0.2-1 microM modified oligodeoxynucleotide to the culture medium of H9 cells chronically infected with the HIV-1LAI isolate of human immunodeficiency virus type 1. We conclude that C-5 propyne oligodeoxynucleotides in accordance with previous findings by others are superior to unmodified phosphorothioates in providing inhibition of HIV-1 in a sequence-dependent manner and that this inhibition can be conferred by oligodeoxynucleotides in free solution.
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PMID:Inhibition of HIV-1 in vitro by C-5 propyne phosphorothioate antisense to rev. 858 62

Modifications of oligodeoxyribonucleotides include the replacement of the backbone phosphodiester groups with phosphorothioate (S-ODNs) groups and the substitution of phosphorothioate (SO-ODNs) groups at both the 3'- and 5'-ends. In assays for HIV, oligomers (S-ODNs) were more active at the micromolar range than were SO-ODNs of the same sequence. Furthermore, the abilities of antisense-, sense-, random-, and mismatched-oligomers, or homo-oligomers containing internucleotidic phosphorothioate linkages to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-, sense-, mismatched-, and homo-oligomers of the same length or with the same internucleotide modification. Five different target sites (gag, pol, rev, tat, and tar) within the HIV genes were also studied with regard to the inhibition of HIV replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of initiation sequences and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting viral replication was also investigated. Of particular interest was the S-ODNs-rev 15 mer, which possessed higher anti-HIV activity than the sense-, random-, mismatched-, and homo-20 mers.
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PMID:Antiviral effect of phosphorothioate oligodeoxyribonucleotides complementary to human immunodeficiency virus. 861 46


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