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

Human immunodeficiency virus 2 (HIV-2) ISY and the newly derived HIV-2KR are infectious molecular clones that yield viruses differing markedly in their abilities to infect and/or induce syncytia in various T- and monocytoid-cell lines. Chimeric viruses were constructed from these two viral genomes to localize the genetic determinants of some of these properties. Envelope sequences, particularly those spanning the CD4 binding site, appear to be critical for the ability of HIV-2KR to infect MOLT-4 clone 8 and SupT1 cells and to efficiently infect the H9 cell line. On the other hand, multiple determinants may contribute to cytopathicity (gp41 and nef) in H9 cells and replication efficiency in monocytic (THP-1) cells.
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PMID:Mapping the determinants of human immunodeficiency virus 2 for infectivity, replication efficiency, and cytopathicity. 848 38

4(S)-(6-Amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol (IsoddA) is the most antivirally active member of a novel class of optically active isomeric dideoxynucleosides in which the base has been transposed from the natural 1' position to the 2' position and the absolute configuration is (S,S). IsoddA was active against human immunodeficiency virus type 1 (HIV-1) (strain IIIB), HIV-2 (strain ZY), and HIV-1 clinical isolates. Combinations of the compound with zidovudine (3'-azido-3'-deoxythymidine), 2',3'-dideoxyinosine, or 5-fluoro-2'-deoxy-3'-thiacytidine showed synergistic inhibition of HIV. A moderate reduction of activity was observed with clinical isolates resistant to zidovudine. An IsoddA-resistant virus (eightfold-increased 50% inhibitory concentration) was selected in vitro by repeated passage of HIV-1 (HXB2) in the presence of increasing concentrations of IsoddA. The reverse transcriptase-coding region of the mutant virus contained a single base change resulting in a change at codon 184 from Met to Val. IsoddA was also active against hepatitis B virus (HBV) in vitro; however, it lacked substantial selective activity in an in vivo HBV model. IsoddA was inefficiently phosphorylated in CEM cells; however, the half-life of the triphosphate was 9.4 h, and IsoddATP was a potent inhibitor of HIV-1 reverse transcriptase, with a Ki of 16 nM. The cytotoxicity 50% inhibitory concentrations of IsoddA were greater than 100 microM for CEM, MOLT-4, IM9, and the HepG2-derived HBV-infected 2.2.15 (subclone P5A) cell lines but were 12 and 11 microM for human granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiviral, metabolic, and pharmacokinetic properties of the isomeric dideoxynucleoside 4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol. 854 Jul 5

Colominic acid is a homopolymer of N-acetylneuraminic acid (NANA), which has an alpha-2,8 ketosidic linkage between its polymer units. In this study, colominic acids were sulfated under different conditions and their antiviral activities against human immunodeficiency virus type 1 (HIV-1) were examined. Sulfated colominic acids, containing 6-12% sulfur, blocked the expression of HIV-1 antigen in MT-4 cells or C8166 cells following exposure to MOLT-4/HTLV-IIIB or HIV-1[GUN-1]. The compounds inhibited syncytium formation upon co-cultivation of MOLT-4 cells (clone 8) with MOLT-4/HTLV-IIIB cells and abolished the production of HIV-1 p24 antigen in culture medium of peripheral blood lymphocytes (PBLs). HIV-1 reverse transcriptase (RT) activity was not directly affected by the drugs. The compounds did not prolong activated partial thromboplastin time (APTT) at 10 and 1.0 microgram/ml, suggesting that they may not have appreciable side effects in vivo. These agents were still able to block the expression of HIV-1 antigen even when the cells were infected with HIV-1 in RPMI-1640 medium containing high percentages of fetal calf serum (FCS). These properties may be therapeutically advantageous if these compounds were considered for possible clinical use.
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PMID:Sulfated colominic acid: an antiviral agent that inhibits the human immunodeficiency virus type 1 in vitro. 879 13

In the search for effective Tat-dependent transcription inhibitors using a screening assay system that has recently been developed, 2-glycineamide-5-chlorophenyl 2-pyrryl ketone (GCPK) has proved to be a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. This compound was inhibitory to HIV-1 replication in both acutely and chronically infected cells. The 50% effective concentration (EC50) of GCPK in acutely infected MOLT-4 and CEM cells was 0.62 and 0.13 microgram/ml, respectively. These values were similar to those of the known Tat-dependent transcription inhibitors Ro5-3335 and Ro24-7429. Like these inhibitors, GCPK could inhibit HIV-1 replication in MOLT-4/IIIB (MOLT-4 cells chronically infected with HIV-1) and tumor necrosis factor-alpha-(TNF-alpha)-induced viral activation in OM10.1 cells (a HL-60 clone latently infected with HIV-1). GCPK is distinct from Ro5-3335 and Ro24-7429 in that this novel Tat-dependent transcription inhibitor has no benzodiazepin ring.
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PMID:2-Glycineamide-5-chlorophenyl 2-pyrryl ketone, a non-benzodiazepin Tat antagonist, is effective against acute and chronic HIV-1 infections in vitro. 889 Nov 64

Incorporation of 2'-beta-fluoro-2',3'-dideoxyadenosine (F-ddA), a recently developed anti-HIV agent, into the cellular DNA of human MOLT-4 cells has been compared with the DNA incorporation seen with fialuridine (FIAU; 1-[2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl]-5-iodouracil), a potent anti-hepatitis B (anti-HBV) nucleoside analogue recently found to cause severe hepatic toxicity in human subjects. At equimolar concentrations (10 microM), incorporation of F-ddA was less than 1% of that for FIAU, a difference attributable to the lack of a 3'-hydroxyl group in the former compound and a consequent inability of F-ddA, unlike FIAU, to form DNA internucleotide linkages.
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PMID:Comparison of the DNA incorporation in human MOLT-4 cells of two 2'-beta-fluoronucleosides, 2'-beta-fluoro-2',3'-dideoxyadenosine and fialuridine. 890 Oct 88

Hairpin antisense oligodeoxyribonucleotides containing 2'-methoxynucleosides were more active in the micromolar concentration range than linear and DNA hairpin phosphorothioate oligonucleotides with the same sequence. Furthermore, the abilities of hairpin antisense and random hairpin phosphorothioate oligonucleotides to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-oligomers of the same length or with the same internucleotide modification. Four different target sites (gag, pol, rev, and tat) within the HIV-1 genome were studied with regard to the inhibition of HIV-1 replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of the initiation sequences of gag were most effective. The [32P]-labeled hairpin phosphorothioate oligonucleotide was rapidly assimilated by MOLT-4 cells, whereas the [32P]-labeled hairpin phosphodiester oligonucleotide was not. In MOLT-4 cells treated with the FITC-hairpin phosphorothioate oligonucleotide containing 2'-methoxynucleosides by a confocal laser scanning microscope, diffuse fluorescence was observed in the cytoplasm. Interestingly, fluorescent signals accumulated in the nuclear region of chronically infected MOLT-4/HIV-1 cells after a 60 min incubation.
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PMID:Hairpin antisense oligonucleotides containing 2'-methoxynucleosides with base-pairing in the stem region at the 3'-end: penetration, localization, and Anti-HIV activity. 892 Sep 60

CD44 is known to interfere in HIV replication and to participate in many physiological processes such as lymphocyte binding to high endothelial venules of lymphoid tissue, lymph nodes, and mucosal endothelium. The T cell lines MOLT-4 and CEM, and CEM subclones were infected with the HIV-1 LAI strain and monitored for the expression of CD44 during the course of chronic virus production until the infected cells were at the stage of latent infection. The levels of CD44 protein expression were quantified using cell surface immunostaining and biotinylation. The maturation of CD44 molecules was evaluated by metabolic sulforadiolabeling and CD44 mRNA was visualized by Northern blot analysis. We show a downmodulation of CD44 expression in infected T cell lines and subclones. This phenomenon was most evident at the stage of latent infection. Then, CD44 molecules were undetectable at both the protein and mRNA levels in latently infected CEM cells and CEM subclones. In addition, the 97-kDa standard CD44 isoform showed a shift upward, while detectable during the stage of chronic virus production. In latently infected MOLT-4 cells, the CD44 protein levels were dramatically decreased; CD44 mRNA was detected, but the sizes differed from the mRNA in uninfected cells. Since CD44 is known to regulate in part lymphocyte homing and HIV replication, the alterations that were observed in the expression of this molecule could interfere with the particular homing of HIV-infected cells and/or viral latency.
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PMID:Alteration of CD44 expression in HIV type 1-infected T cell lines. 894 96

We evaluated the cytotoxic effects of various human immunodeficiency virus (HIV-1) reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine, stavudine, and nevirapine) on HIV-1-infected and uninfected T cell lines. Among the compounds, only stavudine (not the others) proved to be more cytotoxic to MOLT-4/IIIB cells (MOLT-4 cells chronically infected with HIV-1) than to uninfected MOLT-4 cells. Its 50% cytotoxic concentrations were 59.8 and 2.2 microM for MOLT-4 and MOLT-4/IIIB cells, respectively. Stavudine was also more cytotoxic to CEM/ROD (CEM cells chronically infected with HIV type 2) than to uninfected CEM cells. Microscopic analysis revealed that stavudine induced apoptosis in MOLT-4/IIIB cells. Apparent chromatin condensation in the nucleus was observed by electron microscopy. Furthermore, a DNA fragmentation ladder was detected by agarose gel electrophoresis. Addition of thymidine to the culture medium could rescue the cells from stavudine-induced apoptosis. The expression of anti-apoptotic protein Bcl-2 was partially downregulated in MOLT-4/IIIB cells after treatment with stavudine. This downregulation was not identified in MOLT-4 cells. These results indicate that stavudine selectively induces apoptosis in HIV-1-infected T cells and may have potential as a novel strategy for effective chemotherapy of the acquired immune deficiency syndrome (AIDS).
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PMID:Stavudine selectively induces apoptosis in HIV type 1-infected cells. 900 5

Chloropeptins I and II, which are gp120-CD4 binding inhibitors, were isolated as pale yellow-brown powders from the mycelia of a soil actinomycete, Streptomyces sp, WK-3419. Their physico-chemical properties showed that they are chlorinated peptides. Chloropeptin I (C61H45N7O15Cl6) is a novel compound, but chloropeptin II was identified as complestatin. Both compounds inhibited gp120-CD4 binding (IC50: 1.3 and 2.0 microM, respectively), the cytopathic effect of HIV in MT-4 cells (EC50: 1.6 and 1.7 microM, respectively) and syncytium formation in co-cultured HIV-1-infected and uninfected MOLT-4 cells (IC50. 0.5 and 1.1 microM, respectively). Chloropeptin I was synergistic in the inhibition of the cytopathic effect when combined with other anti-HIV drugs such as zidovudine (AZT), didanosine (ddI), zalcitabine (ddC) and nevirapine.
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PMID:Chloropeptins, new anti-HIV antibiotics inhibiting gp120-CD4 binding from Streptomyces sp. I. Taxonomy, fermentation, isolation, and physico-chemical properties and biological activities. 906 67

With the results from the Delta and ACTG 175 clinical trials clearly showing an increased benefit of two drugs over monotherapy, combination nucleoside analog therapy looks set to play a major role in the battle against HIV. It is therefore essential that suitable combinations of drugs are used in clinical trials. We investigated the intracellular activation of zidovudine (ZDV), zalcitabine (ddC), and lamivudine (3TC) in MOLT-4 cells in two- and three-drug combinations at clinically achieved concentrations. The phosphorylation of ZDV and 3TC to their active triphosphate anabolites was not affected by the presence of the other drugs studied. However, the phosphorylation of ddC was significantly inhibited when incubated with 3TC, resulting in levels of ddC triphosphate (ddC-TP) less than 50% of control values. This can be explained by the requirement of both nucleoside analogs for the enzyme deoxycytidine kinase to carry out the initial step in their phosphorylation pathways, and by the comparatively low plasma concentrations of ddC achieved in vivo. These results suggest that regimens containing nucleoside analogs should be designed taking into account potential interactions affecting phosphorylation.
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PMID:In vitro screening of nucleoside analog combinations for potential use in anti-HIV therapy. 910 Sep 89


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