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)

The conversion of endogenous or exogenous murine retroviruses to a leukemogenic phenotype involves recombination with retroviral sequences present in host genomic DNA. In the 129 Gix+ inbred strain, these endogenous sequences are replication defective but still express retroviral proteins under the apparent transcriptional control of the Gv-1 regulatory locus. To study the protein-coding potential of Gv-1-regulated endogenous retroviral loci, we used oligonucleotide probes directed to env deletion breakpoints identified in previously characterized cDNA clones. Four endogenous retroviral loci were isolated from a library of 129 Gix+ genomic DNA with these probes. Three loci cloned with the env deletion probe del env-1 had virtually identical proviral inserts by restriction analysis. A unique locus was identified and cloned with the del env-2 probe, which must therefore represent a Gv-1-responsive element. Restriction enzyme and nucleotide sequence analyses indicated that the del env-1 and del env-2 loci represented members of the polytropic and modified polytropic classes of endogenous retrovirus, respectively. Despite this divergence, members of both classes contained identical deletions of 19 nucleotides within p30gag and of 1,474 nucleotides from p10gag into the reverse transcriptase-coding region of pol, suggesting that a recombination event had occurred between these proviral sequences prior to insertion within the genome. The del env-1 and del env-2 loci retained coding capacity for truncated gag polyproteins, confirmed by in vitro translation and immunoprecipitation of the protein products. Nucleotide sequence comparison of the untranslated leader (L) regions of the del env-1 and del env-2 loci to a replication-competent ecotropic virus indicated regions that might be important to dispersion of these endogenous retroviral elements throughout the host genome.
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PMID:Truncated gag products encoded by Gv-1-responsive endogenous retrovirus loci. 278 92

Several single-cell clones were isolated from a fetal lamb kidney cell line (FLK) persistently infected with bovine leukemia virus (BLV). The majority of isolated cell clones were virus productive, several were nonproductive based on the determination of the activity of reverse transcriptase and production of 3H-uridine labeled virus particles. Two nonproductive clones, NP-1 and NP-2, were further characterized in comparison with the virus productive cells. All clones contained three integrated BLV proviruses in the nonproducer cells. The virus specific mRNAs were expressed both in the virus productive and nonproductive cells. The virus-specific protein products were found different in the nonproducing cells. The gag pol precursor Pr145 was missing in NP-1 cells, in NP-2 its Mr was 120 only. In NP-2 cells the precursors Pr70gag and Pr45gag were absent. The env precursor gPr72 and both of the two glycoproteins were detected. The nonproductive cells NP-2 produced mainly env gene products, therefore they were tested as a potential material for anti-BLV vaccine. The NP-2 cells after inoculation to rats and cattle were able to induce formation of neutralizing antibodies directed against the env gene products.
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PMID:Bovine leukemia virus: isolation and characterization of nonproducer cell clones. 282 41

A retrovirus packaging cell line was constructed by using portions of the Moloney murine leukemia virus in which the gag, pol, and env genes of the helper virus were separated onto two different plasmids and in which the psi packaging signal and 3' long terminal repeat were removed. The plasmid containing the gag and pol genes and the plasmid containing the env gene were cotransfected into NIH 3T3 cells. Clones that produced high levels of reverse transcriptase and env protein were tested for their ability to package the replication-defective retrovirus vectors delta neo and N2. One of the gag-pol and env clones (GP+E-86) was able to transfer G418 resistance to recipient cells at a titer of as high as 1.7 X 10(5) when it was used to package delta neo and as high as 4 X 10(6) when it was used to package N2. Supernatants of clones transfected with the intact parent gag-pol-env plasmid 3P0 had comparable titers (as high as 6.5 X 10(4) with delta neo; as high as 1.7 X 10(5) with N2). Tests for recombination events that might result in intact retrovirus showed no evidence for the generation of replication-competent virus. These results suggest that gag, pol, and env, when present on different plasmids, may provide an efficient and safe packaging line for use in retroviral gene transfer.
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PMID:A safe packaging line for gene transfer: separating viral genes on two different plasmids. 283 75

The human immunodeficiency virus is a member of the lentivirus subfamily of the retrovirus family. Retroviruses are RNA viruses which code for an RNA-dependent DNA polymerase (reverse transcriptase), which transcribes the RNA genome into a DNA provirus which, on integration with the host DNA, directs the synthesis of new virions. The RNA genome consists of a gag gene, which codes for the viral core proteins, a pol gene, which codes for the reverse transcriptase, an env gene, which codes for the glycoproteins of the viral envelope, and several genes (tat, rev, vif, vpr, and nef), that code for regulatory proteins. At each end of the genome are long terminal repeats, that contain regulatory elements for transcription. There are 3 subfamilies of Retroviridae (Oncovirinae, Spumavirinae, and Lentiverinae). The Lentiverinae ("slow viruses") include the bovine immunodeficiency virus (BIV), the feline immunodeficiency virus (FIV), the human immunodeficiency viruses (HIV), and the simian immunodeficiency viruses (SIV). SIV has been isolated from macaques (mac), African green monkeys (agm), sooty mangabeys (sm), and mandrills (mnd). Only SIVmac causes an AIDS-like disease in its natural host, but it is genetically closer to HIV-2 than to HIV-1. SIVsm causes an AIDS-like disease in macaques, but not in the sooty mangabey. Monkeys infected with SIV develop diarrhea, wasting, decrease in T4 lymphocytes, lymphadenopathy, development of giant cells, and encephalitis, as well as opportunistic infections. Kaposi's sarcoma, however, has not been found in SIV-infected primates. Virus is recovered from peripheral blood mononuclear cells and the brain. SIV models are useful for understanding the natural history of primate lentiviruses, for defining the pathogenesis of AIDS, and for developing vaccines. The ideal model would be one in which HIV causes AIDS, but so far only chimpanzees and gibbons have successfully been infected with HIV-1, and although virus, is recovered from peripheral blood mononuclear cells of chimpanzees within 2 weeks of infection, and 2 animals have lost antibodies to the p24 protein, none has so far developed clinical AIDS. Attempts to develop vaccines to immunize chimpanzees are continuing. Nonprimate lentiviruses include the visna virus, the feline immunodeficiency virus, and the bovine immunodeficiency virus. The visna virus infects fibroblasts by fusion of the viral envelope with the plasma membrane of the fibroblast; it infects macrophages by endocytosis. Infected macrophages regulate the production and dissemination of viral particles. The feline immunodeficiency virus infects T-lymphocytes of cats and produces oral, gastrointestinal and respiratory pathology as well as lymphadenopathy and opportunistic infections. Bovine immunodeficiency-like virus causes a generalized lymphadenopathy similar to that seen in AIDS-related complex.
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PMID:Animal models for HIV infection and AIDS: memorandum from a WHO meeting. 285 Jan 18

The complete nucleotide sequence of a mouse retro-element is presented. The cloned element is composed of 4,834 base pairs (bp) with long terminal repeats of 568 bp separated by an internal region of 3,698 bp. The element did not appear to have any open reading frames that would be capable of encoding the functional proteins that are normally produced by retro-elements. However, some regions of the genome showed some homology to retroviral gag and pol open reading frames. There was no region in VL30 corresponding to a retroviral env gene. This implies that VL30 is related to retrotransposons rather than to retroviruses. The sequence also contained regions that were homologous to known reverse transcriptase priming sites and viral packaging sites. These observations, combined with the known transcriptional capacity of the VL30 promoter, suggest that VL30 relies on protein functions of other retro-elements, such as murine leukemia virus, while maintaining highly conserved cis-active promoter, packaging, and priming sites necessary for its replication and cell-to-cell transmission.
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PMID:Complete nucleotide sequence of a mouse VL30 retro-element. 285 Apr 74

The human spumaretrovirus (HSRV) isolated from a nasopharynx carcinoma patient 17 years ago has a RNA genome 11 kb in size. It encodes besides the gag, pol, and env genes several novel genes (S1 and bel 1, 2, and 3) that are comparable to the regulatory genes R, X, tat, art, and 3'-orf of the human (HIVs) and simian immunodeficiency viruses (SIVs) with respect to genomic location and to sizes of the putative gene products. A comparison between the HIV protein sequences of the pol and the novel genes to the corresponding gene product sequences of HSRV revealed that HSRV is related to the lentiviruses but occupies a distinct phylogenetic placement of its own. A detailed analysis of the reverse transcriptase domain allows the construction of a phylogenetic tree for the known retroviral subfamilies and/or groups, including the oncoviruses, the lentiviruses, the spumaviruses, the HLTV-BLV group, and the D-type viruses. Regions of the putative novel HSRV gene products with segmental protein sequence homology to the regulatory protein of other human retroviruses are discussed. The results strengthen the view that HSRV and its novel genes should be studied in comparison to the new genes of acquired immunodeficiency syndrome (AIDS) viruses and human T cell leukemia viruses (HTLV).
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PMID:Genomic organization of the human spumaretrovirus and its relatedness to AIDS and other retroviruses. 285 7

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

A chemically synthesized peptide corresponding to the amino acid sequence 503-532 of gp160 of human immunodeficiency virus (HIV) was used to generate monoclonal antibodies reactive with the env glycoprotein gp120. One monoclonal antibody, 120-1, was isolated that reacted with the peptide and with HIV antigen(s). Western blot analysis showed reactivity with two bands of 120 kDa and 88 kDa. 120-1 reacted in indirect immunofluorescence with 15-20% of infected human T cell line A3.01 as early as 4 days post in vitro infection, 2-3 days prior to detectable reverse transcriptase activity in supernatant fluids.
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PMID:Human immunodeficiency virus gp120 glycoprotein detected by a monoclonal antibody to a synthetic peptide. 302 2

We sequenced two recombinant DNA clones constituting a single provirus of the milk-transmitted mouse mammary tumor virus characteristic of BR6 mice. The complete provirus is 9,901 base pairs long, flanked by 6 base-pair duplications of cellular DNA at the site of integration. Five extensive blocks of open reading frame corresponding to the gag gene, the presumed protease, the pol and env genes, and the open reading frame orf within the long terminal repeat of the provirus were readily discernible. Translation of gag, protease, and pol involved three different translational reading frames to produce the three overlapping polyprotein precursors Pr77, Pr110, and Pr160 found in virus-infected cells. Synthesis of the reverse transcriptase and endonuclease therefore required two separate frameshifts to suppress the termination codons at the ends of the Pr77 and Pr110 domains. Direct evidence is presented for translational readthrough of both stop codons in an in vitro protein synthesis system.
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PMID:Complete nucleotide sequence of a milk-transmitted mouse mammary tumor virus: two frameshift suppression events are required for translation of gag and pol. 302 77

Previously, human diploid fibroblasts from some donors infected in vitro by avian sarcoma virus (ASV) were transformed and found, by electron microscopy, to produce small numbers of virus particles that were infectious by bioassay; also, a line of human osteosarcoma cells infected with ASV developed additional characteristics of transformation and released a small number of infectious virus particles. In this study the complete proviral sequence was shown to be integrated in the genome of these cells. The env-related proteins gp85 and gp37 and the gag-related proteins pr76, pr60, and p19 can be detected in cytoplasmic extracts of ASV-infected human cells. Comparable amounts of pp60v-src were found in human and avian cells infected with ASV. The associated kinase activity in infected human cells was dramatically increased as compared to that of uninfected controls; the enzyme had the same cation and substrate requirements as those from ASV-transformed avian cells. Replicating particles from infected human cells were purified and were significantly modified compared to those from avian hosts as shown by a) higher specific gravity, b) the presence of RSV gag-related but not env-related antigens, and c) the fact that the virus-associated reverse transcriptase preferred the divalent cations Mn2+ and Fe2+ over Mg2+.
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PMID:Integration and expression of provirus in human cells transformed by avian sarcoma virus. 303 82


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