Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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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)

Preparations of recombinant reverse transcriptase RSV were isolated from E. coli HB101/pMF14 cell cultures. The enzyme purified to homogeneity was shown to be made up of two subunits with molecular masses of 97 +/- 4 and 61 +/- 3 kDa. A comparison of enzymatic properties of recombinant transcriptase to those of the enzyme isolated from the RSV (Rauss sarcoma) virus demonstrated that in the preparations under study the recombinant reverse transcriptase exists in a subunit form, alpha beta, and may acquire a relatively stable configuration, alpha 2.
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PMID:[Recombinant RNA-dependent DNA-polymerase from Rous sarcoma virus. Isolation and properties]. 169 35

A new class of compounds, 9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] [(RS)-FPMP] derivatives of purines, is described that has selective activity against a broad spectrum of retroviruses [including human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2)] but not other RNA or DNA viruses. This activity spectrum is completely different from that of the parental compounds, 9-[(2S)-3-hydroxy-2-phosphonylmethoxypropyl] [(S)-HPMP] derivatives of purines, which are active against a broad range of DNA viruses. The racemic (RS)-FPMP derivatives of adenine and 2,6-diaminopurine, termed (RS)-FPMPA and (RS)-FPMPDAP, respectively, are markedly more selective as in vitro antiretroviral agents than their 9-(2-phosphonylmethoxyethyl) (PME) counterparts, PMEA and PMEDAP. Also, (RS)-FPMPA and (RS)-FPMPDAP have a substantially higher therapeutic index in mice in inhibiting Moloney murine sarcoma virus-induced tumor formation and associated death and are markedly less inhibitory to human bone marrow cells than PMEA and PMEDAP. The diphosphate derivative of (RS)-FPMPA [(RS)-FPMPApp] is a potent and selective inhibitor of HIV-1 reverse transcriptase but not of HSV-1 DNA polymerase or DNA polymerase alpha. (RS)-FPMPApp, akin to PMEA diphosphate (PMEApp), acts as a DNA chain terminator. The DNA chain-terminating properties of PMEApp and (RS)-FPMPApp seem to be a prerequisite for acyclic nucleoside phosphonates to exhibit antiretrovirus (i.e., anti-HIV) activity.
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PMID:9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] derivatives of purines: a class of highly selective antiretroviral agents in vitro and in vivo. 171 Dec 14

Phosphonoformate (PFA), a noncompetitive inhibitor of reverse transcriptase (RT), inhibited feline leukemia virus (FeLV) infection of 2 feline cell lines and inhibited progeny virus RT activity in a chronically FeLV-infected cell line. Feline leukemia virus infection of 3201 cells, an FeLV-negative lymphoma cell line, was inhibited by greater than 70% at a concentration of only 1 microM PFA and by greater than 90% at concentrations of 64 to 256 microM PFA, as evidenced by RT activity. However, FeLV antigen expression by 3201 cells remained relatively constant over noncytotoxic concentrations of PFA. Because the persistence of viral antigen expression with concomitant suppression of RT activity appears to be unique and because 3201 cells express small amounts of an endogenous retrovirus (RD-114) and contain endogenous FeLV proviral sequences, a possible role of endogenous retroviruses acting as helper viruses was suggested. Feline leukemia virus infection of 81C cells, a sarcoma-positive, leukemia-negative fibroblast cell line, was inhibited by greater than 50% at a concentration of 64 microM PFA and by greater than 98% at concentrations of 256 to 512 microM PFA, as indicated by suppression of focus formation. The feline lymphoid cell line FL-74 is a large producer of FeLV. When FL-74 cells were cultured in the presence of 256 microM PFA, virus production (virus budding and viral antigen) was not affected, but progeny virus lost RT activity and infectivity. Direct addition of PFA (256 microM) to FeLV also reduced RT activity and infectivity. These data indicate that PFA can directly and rapidly inactivate retrovirus independent of cellular processing, presumably by inhibiting RT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prophylactic and therapeutic effects of phosphonoformate against feline leukemia virus in vitro. 172 22

Enzymological properties of the RNA-directed DNA polymerase associated with the Suncus murinus mammary tumor virus (Sm-MTV) was investigated and its antigenic relatedness to other retroviral DNA polymerases was examined. The enzyme exhibited higher activity in the presence of Mg2+ than in the presence of Mn2+ with endogenous RNA as well as with almost all of the synthetic template X primers tested. Mg2+ was also effective with poly(2'-O-methylcytidylate) X oligodeoxyguanylate which was known to be specific for Mn2+. To examine the immunological relatedness of this enzyme with other retroviral DNA polymerases, remaining Sm-MTV DNA polymerase activity was measured after treatment of this enzyme with various antisera prepared against each of the reverse transcriptases of Mason-Pfizer monkey virus (MPMV), murine mammary tumor virus (MuMTV), simian sarcoma virus-simian sarcoma associated virus (SSV/SSAV), and Rauscher murine leukemia virus (RLV). No inhibition of the Sm-MTV enzyme activity was observed when treated with the latter three antisera with which the DNA polymerase activities of the corresponding retroviruses were fully inhibited. Only the antiserum against MPMV-enzyme, however, was found to slightly inhibit the Sm-MTV enzyme activity. These results indicate that Sm-MTV DNA polymerase has similar enzymological properties to those of MPMV and MuMTV and shares some common antigenic determinant group(s) with MPMV DNA polymerase.
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PMID:Biochemical and immunological characterization of Suncus murinus mammary tumor virus DNA polymerase. 241 16

We have found human DNA to contain a number of sequences related to simian sarcoma associated virus (SSAV). One of these sequences was isolated from a human genomic library. The molecular clone, termed S71, contains regions homologous to SSAV gag and pol fragments and SSAV LTR. Furthermore, hybridization experiments and DNA sequencing revealed distinct homologies to the reverse transcriptase coding region of several other retroviruses including baboon endogenous virus (BaEV) and murine leukemia viruses (MuLV) as well as retrovirus-like elements. Some sequence homology was also found with the C-type retrovirus-related multicopy human clone 4-1. S71 is present in only one copy per human genome equivalent and exhibits an EcoRI restriction fragment length polymorphism.
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PMID:Isolation of an SSAV-related endogenous sequence from human DNA. 243 42

A series of 5'-phosphorylated derivatives of 3'-azido-2',3'-dideoxythymidine (AzddThd), including AzddThd 5'-mono- and 5'-triphosphate, alpha, beta-methylene AzddThd-5'-diphosphate, alpha,beta-methylene AzddThd-5'-triphosphate, and beta,gamma-methylene AzddThd-5'-triphosphate, were evaluated for their cytostatic and anti-retrovirus properties, and their inhibitory effects on the reverse transcriptases of Moloney murine leukemia virus and human immunodeficiency virus. In contrast with the 5'-mono- and 5'-triphosphates of AzddThd, which showed cytostatic and anti-retrovirus activities comparable to those of AzddThd, the alpha,beta-methylene 5'-phosphonates of AzddThd were considerably less cytostatic and also much less inhibitory to cell transformation by Moloney murine sarcoma virus and cytopathogenicity of human immunodeficiency virus. The decreased biological activity of the phosphonate derivatives of AzddThd is most likely due to the resistance of these compounds to phosphorolytic attack by phosphodiesterases and phosphatases, and the reduced affinity for the retrovirus-associated reverse transcriptase.
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PMID:Alpha, beta- and beta, gamma-methylene 5'-phosphonate derivatives of 3'-azido-2',3'-dideoxythymidine-5'-triphosphate. Correlation between affinity for reverse transcriptase, susceptibility to hydrolysis by phosphodiesterases and anti-retrovirus activity. 245 21

Human continuous bone marrow cultures were established from intraoperative marrow specimens and infected with amphotropic murine leukemia virus (Am-MuLV) pseudotypes of Kirsten or Harvey murine sarcoma virus, and the biologic effects were compared with mouse continuous bone marrow cultures. Cultures were tested for production of total nonadherent granulocytes and granulocyte-macrophage progenitor cells (GM-CFUc); virus replication by supernatant reverse transcriptase activity; percentage of adherent and nonadherent cells and GM-CFUc that released virus by infectious center assay; and for synthesis of Harvey ras p21 protein. High-efficiency, stable Am-MuLV infection of over 90% of human marrow-culture nonadherent and adherent cells and both seven- and 14-day GM-CFUc were detected as Kirsten or Harvey pseudotype virus release by infectious center assay. Synthesis of Harvey ras p21 was detected in the adherent and nonadherent cell populations of human as well as mouse continuous marrow cultures infected with Kirsten or Harvey pseudotype virus. In contrast to data with mouse cultures, cumulative production of GM-CFUc and differentiated granulocytes in human cultures was not detectably altered by Harvey or Kirsten virus infection, and all cultures ceased to produce hematopoietic cells by 20 weeks. Of 54 virus-infected cultures in ten separate experiments, 13 produced a second peak of nonadherent cells (greater than 10(5) per flask) after 20 weeks, significantly more frequently than did control uninfected cultures (one of 32). When subcultured, these harvests produced permanent Epstein-Barr virus (EBV)-transformed pre-B cell lines that released the original inoculating pseudotype virus. Thus, Am-MuLV is a potentially valuable vector for inserting genetic sequences by recombinant techniques into human hematopoietic and stromal cells in culture; however, activation of EBV may be a significant complication.
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PMID:Amphotropic retrovirus vector transfer of the v-ras oncogene to human hematopoietic and stromal cells in continuous bone marrow cultures. 257 39

3'-Azido-2',3'-dideoxythymidine (az-T) inhibited effectively the reproduction of some retroviruses; among these viruses were the four serological subgroups of sarcoma Raus virus in chicken embryo, avian myeloblastosis virus and erythroblastosis virus in chicken. This inhibition was specific towards retroviruses and practically was not observed in the case of infections DNA- and RNA-genome model viruses of vaccinia and influenza, at whose reproduction reverse transcriptase is not involved. Three other 3'-modified nucleosides did not block the above-listed retroviruses. For chickens, az-T showed low toxicity. The molecular mechanisms of the action of az-T are discussed.
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PMID:[The effect of 3'-azido-2',3'-dideoxythymidine on experimental viral infections]. 282 79

The RNA expression of a series of replication-defective recovered avian sarcoma viruses (rASVs) were studied. Abnormal-sized viral RNAs, both larger and smaller than the genome, were observed in the nonproducer cells infected with rASVs containing env and pol deletions. Each nonproducer clone contained a single provirus integrated at a unique site and expressed a unique RNA pattern. Upon rescuing of the sarcoma virus with a helper virus and subsequent cloning, the RNA pattern of individual nonproducer clones again displayed variation according to the integration sites. This was not seen in nondefective rASV or in rASVs containing only an env deletion. The aberrant RNA expression did not result from the lack of reverse transcriptase activity per se, since neither nonconditional nor temperature-sensitive mutants of RSV expressed abnormal viral RNAs in the absence of a functional reverse transcriptase. The abnormal RNA patterns could not be corrected in trans by helper virus functions. The unusual-sized RNAs in env- pol- rASV-infected cells are not due to splicing to alternative acceptor sites for src mRNA because there are no extra viral sequences between the 5' leader and the src sequences; instead, they are due to the presence of extra sequences, most likely of cellular origin, at the 3' ends of the viral RNAs. Based upon the extent of deletions in the viral genomes, the data suggest that deletion in the 3' pol region of those rASVs results in a cis effect on the transcription and processing of the 3' ends of viral RNAs. The unusual-sized viral RNAs are most likely due to read-through transcription from the right-hand terminus of provirus into downstream cellular sequences, followed by cleavage and polyadenylation at multiple sites of the 3' region of the RNA transcripts. The extent of read-through transcription appears to depend on the chromosomal location of the provirus.
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PMID:Deletion in the 3' pol sequence correlates with aberration of RNA expression in certain replication-defective avian sarcoma viruses. 298 7

Hepatitis B virus (HBV), although classified as a double-stranded DNA virus, has been shown recently to replicate by reverse transcription of an RNA intermediate. Also, the putative viral polymerase has been found to share amino acid homology with reverse transcriptase of retroviruses. Using computer-assisted DNA and protein sequence analyses, we examined the genomes of 13 hepadnavirus isolates (nine human, two duck, one woodchuck, and one ground squirrel) and found that other conserved regions of the hepadnavirus genome share homology to corresponding regions of the genomes of type C retroviruses and retrovirus-like endogenous human DNA elements. Specifically, the most highly conserved sequence of the HBV genome, positioned at or near the initiation site for first-strand HBV DNA synthesis, is homologous over 67 nucleotides to the U5 region, a comparable region in retrovirus long terminal repeats. Within a highly conserved (i.e., 90%) 16-nucleotide sequence a heptanucleotide sequence CCTTGGG is 97% homologous between 27 virus isolates. Also, we found that the highly conserved HBV core, or nucleocapsid, protein shares 41% homology over 98 amino acids with the carboxyl-terminal region of the p30 gag nucleocapsid protein of type C retroviruses. In both cases, as with the previously reported polymerase homology, HBV is most homologous to the murine leukemia/sarcoma retroviruses. Further analysis revealed additional similarities between hepadnavirus and retroviral genomes. Taken together, our results suggest that HBV and retroviruses have a common evolutionary origin, with HBV arising through a process of deletion from a retrovirus, or retrovirus-like, progenitor.
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PMID:Common evolutionary origin of hepatitis B virus and retroviruses. 345 14


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