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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transduction of cellular oncogenes by retroviruses is thought to be a multistep process, involving transcriptional activation of a cellular gene by upstream proviral integration and joining of cellular DNA to retroviral transcriptional signals, followed by copackaging and recombination with a helper virus genome during reverse transcription. To examine the molecular mechanism of the reverse transcriptase-mediated recombination, we introduced into mouse fibroblast cells a variety of constructs in which the neo selectable marker was joined to flanking retroviruslike or cell-like sequences. After superinfection and copackaging with a replication-competent Mo-MuLVsupF virus, the formation of recombinant neo transducing viruses was assessed in a second round of virus infection by the ability to confer G418 resistance to infected cells. Our results showed that recombinant neo proviruses were generated from neo RNA containing either a 5' or 3' retroviral end, implying that one recombination event with helper virus RNA was sufficient to incorporate the neo gene into proviral DNA. Recombination occurred with an apparent frequency of 10(-4) to 10(-5) per replication cycle in the absence of homology between the two recombining partners. This frequency, however, increased at least 100-fold if homology was provided at the site of recombination. Our results support the hypothesis that neo-transducing viruses arise via reverse transcriptase-mediated recombination of RNA rather than by recombination proceeding through DNA intermediates. Unexpectedly, removal of the retroviral packaging site psi reduced the number of neo recombinants only slightly. Our data indicated that although RNAs lacking the psi site are poorly packaged into virions, those RNAs that are included in the virions undergo frequent recombination, even if there is no selection for recombination. Many of the neo recombinants formed with the psi- constructs had undergone additional recombinations and often incorporated the psi site from the helper RNA.
J Virol 1990 Dec
PMID:Transduction of cellular neo mRNA by retrovirus-mediated recombination. 170 Aug 24

A series of chimeric clones of human immunodeficiency virus type 1 and simian immunodeficiency virus isolated from an African green monkey was constructed in vitro. In transient transfection experiments, all clones produced virion-associated reverse transcriptase, gag proteins, and env proteins. Eight out of 10 chimeric viruses clearly grew in the human CD4+ cell line C8166. Susceptibility of other CD4+ cell lines, MT-4, A3.01, and Molt4 clone 8, to infection with these viruses was also demonstrated.
J Virol 1990 Dec
PMID:Generation and characterization of infectious chimeric clones between human immunodeficiency virus type 1 and simian immunodeficiency virus from an African green monkey. 170 Aug 27

The ability of complement to inactivate human immunodeficiency virus (HIV) in the presence of specific antibody was evaluated. HIV was treated with complement and/or antibody, and then its titer was determined on the CD4+ H9 cell line. While complement alone had no effect on the HIV titer, complement plus subneutralizing levels of antibody resulted in titer reductions. Complement sources deficient in membrane attack component C5 or C8 did not inactivate antibody-treated HIV, suggesting that neutralization occurred via lysis. This possibility was investigated by assessing release of reverse transcriptase (RT) from the virion. Antibody plus complement, but neither reagent alone, released RT from HIV in a dose-dependent manner. Release of RT did not occur with C5- or C8-deficient sera, also indicating a requirement for membrane attack components. These studies show that complement can neutralize HIV via the classical complement pathway and that this neutralization occurs via C5b-9-mediated viral lysis. Thus, complement may play a major role in resistance to disease by lysing HIV and preventing infection of Fc- and complement receptor-positive cells, as well as CD4+ cells.
J Virol 1990 Dec
PMID:Neutralization of human immunodeficiency virus type 1 by complement occurs by viral lysis. 170 Aug 28

Ribavirin inhibits the human immunodeficiency virus reverse transcriptase in an in vitro reaction. Ribavirin-5'-diphosphate was close to 40% more inhibitory than ribavirin-5'-triphosphate. Unphosphorylated ribavirin had a reduced, but detectable, effect as an inhibitor, compared with the phosphorylated forms. The compounds seem to have a direct effect on the viral polymerase, and no chain termination was observed in the presence of ribavirin-5'-triphosphate. Combination of any of the ribavirin derivatives tested with 3'-azido-3'-deoxythymidine (zidovudine)-5'-triphosphate resulted in an increase of its anti-human immunodeficiency virus reverse transcriptase activity in the in vitro assay.
Mol Pharmacol 1990 Dec
PMID:Ribavirin is an inhibitor of human immunodeficiency virus reverse transcriptase. 170 Dec 13

Bleomycin is an antitumor agent whose activity has long been thought to derive from its ability to degrade DNA. Recent findings suggest that cellular RNA may be a therapeutically relevant locus. At micromolar concentrations, Fe(II)-bleomycin readily cleaved a Bacillus subtilis tRNAHis precursor in a highly selective fashion, but Escherichia coli tRNA(Tyr) precursor was largely unaffected even under more forcing conditions. Other substrates included an RNA transcript encoding a large segment of the reverse transcriptase from human immunodeficiency virus 1. RNA cleavage was oxidative, approximately 10-fold more selective than DNA cleavage, and largely unaffected by nonsubstrate RNAs. RNA sequence analysis suggested recognition of RNA tertiary structure, rather than recognition of specific sequences; subsets of nucleotides at the junction of single- and double-stranded regions were especially susceptible to cleavage. The ready accessibility of cellular RNAs to xenobiotic agents, the high selectivity of bleomycin action on RNAs, and the paucity of mechanisms for RNA repair suggest that RNA may be a therapeutically relevant target for bleomycin.
Proc Natl Acad Sci U S A 1990 Dec
PMID:Site-specific cleavage of RNA by Fe(II).bleomycin. 170 Dec 59

The region (retron-Ec67) required for the biosynthesis of a branched-RNA-linked multicopy single-stranded DNA (msDNA-Ec67) from a clinical isolate of Escherichia coli was mapped at a position equivalent to 19 min on the K-12 chromosome. The element containing the retron consisted of a unique 34-kilobase sequence that was flanked by direct repeats of a 26-base-pair sequence found in the K-12 chromosomal DNA. This suggests that the 34-kilobase element was probably integrated into the E. coli genome by a mechanism related to transposition or phage integration. In the 34-kilobase sequence an open reading frame of 285 residues was found, which displays 44% sequence identity with the E. coli Dam methylase. Interestingly, there are three GATC sequences, the site of Dam methylation, in the promoter region of the gene for reverse transcriptase.
Proc Natl Acad Sci U S A 1990 Dec
PMID:Retron for the 67-base multicopy single-stranded DNA from Escherichia coli: a potential transposable element encoding both reverse transcriptase and Dam methylase functions. 170 Dec 61

A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT). One compound, BI-RG-587, had a Ki of 200 nanomolar for inhibition of HIV-1 RT that was noncompetitive with respect to deoxyguanosine triphosphate. BI-RG-587 was specific for HIV-1 RT, having no effect on feline and simian RT or any mammalian DNA polymerases. BI-RG-587 inhibited HIV-1 replication in vitro as demonstrated by in situ hybridization, inhibition of protein p24 production, and the lack of syncytia formation in cultured human T cell lines and freshly isolated human peripheral blood lymphocytes. Cytotoxicity studies of BI-RG-587 on human cells showed a high therapeutic index (greater than 8000) in culture.
Science 1990 Dec 07
PMID:Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. 170 68

Malignant lymphomas were observed in 38% (9 of 24) of simian immunodeficiency virus (SIV)-infected cynomolgus monkeys (Macaca fascicularis) 5 to 15 months after inoculation with SIV strain SMM3. Lymphomagenesis in the SIV-infected monkeys was not related directly to the SIV-infectious dose given. All SIV-infected animals developed severe immunodeficiency. No significant difference in immunodeficiency was observed between tumor-bearing and non-tumor-bearing animals. In contrast, no lymphomas were observed in a comparable group of HIV-2-infected monkeys, which did not develop immunodeficiency; nor did the noninfected control monkeys. All 9 SIV-related tumors were high-grade B-cell lymphoblastic or pleomorphic lymphomas with extranodal, disseminated growth. Most tumors showed marked infiltration by monocytes and CD8+ T lymphocytes. Occasional tumor infiltrating cells showed immunohistochemical reaction for SIV. The cells of two tumors were established in vitro and shown to be of B-cell phenotype. The tumor cell cultures showed no reverse transcriptase activity and no evidence of virus infection by electron microscopy. Our observations indicate that SIV-induced immunodeficiency in cynomolgus monkeys also mimics HIV infection and AIDS in humans with regard to increased lymphomagenesis and type of lymphomas.
Am J Pathol 1990 Dec
PMID:Malignant lymphomas in cynomolgus monkeys infected with simian immunodeficiency virus. 170 62

Retroviral RNA-dependent DNA polymerase (reverse transcriptase or RT) uses the 3'OH end of a cellular tRNA as primer to initiate DNA synthesis. Previous work with avian retrovirus has shown that reverse transcriptase is implicated in the selection of cellular virion-encapsidated tRNAs and has shown that the primer tRNA is positioned on the primer binding site near the 5' end of the viral RNA. These mechanisms support the idea that the retroviral polymerase should form complexes with primer tRNA and the specific encapsidated ones. The genomic sequence of human immunodeficiency virus (HIV) allows the prediction that tRNA(Lys3) is the natural primer. In this article we show, using the mobility shift assay, that recombinant HIV reverse transcriptase is able to form a complex with bovine tRNA(Lys.) By fluorescence studies and alpha-chymotrypsin analysis we have observed a modification of the enzyme conformation when reverse transcriptase is bound to the putative primer tRNA. This structural change is specific for tRNA(Lys) although the retroviral polymerase is able to interact with other tRNAs.
FEBS Lett 1990 Dec 17
PMID:Interactions with tRNA(Lys) induce important structural changes in human immunodeficiency virus reverse transcriptase. 170 35

We investigated the inhibitory effects of aurochloric acid (AuCl4H) on reverse transcriptase (RT) derived from avian myeloblastosis virus and DNA polymerase alpha (pol. alpha) purified from HeLa S3 cells. The activities of RT, pol. alpha and E. coli DNA polymerase I (pol. I) with dTTP as the substrate were inhibited 50% at AuCl4H concentrations of 18 microM, 43 microM and 230 microM, respectively. AuCl4H inhibited RT activity competitively with respect to the substrate, dTTP, and uncompetitively with the template/primer, (rA)n(dT)12-18. In assays with dGTP as the substrate, 50% inhibitions of RT, pol. alpha and pol. I activities were observed at AuCl4H concentrations of 100 microM, 450 microM and 580 microM, respectively. AuCl4H inhibited RT activity uncompetitively with respect to the substrate, dGTP, and noncompetitively with the template/primer, (rC)n(dG)12-18. AuCl4H at concentrations causing more than 50% inhibition of RT activity had little inhibitory effect on the colony-forming ability of HeLa cells or their syntheses of DNA, RNA and protein.
Jpn J Cancer Res 1990 Dec
PMID:Inhibition of avian myeloblastosis virus reverse transcriptase by aurochloric acid. 170 21


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