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)

Simian retroviruses closely related to human T-cell leukemia virus (HTLV) were isolated by establishing virus-producing lymphoid cell lines from 7 species of non-human primates. By co-cultivation with human umbilical cord-blood cells and/or in the presence of interleukin-2, lymphoid cell lines were successfully established from the chimpanzee. African green monkey, pig-tailed macaque, red-faced macaque, Formosan monkey, Japanese monkey and bonnet monkey that had antibodies against HTLV antigens. These cell lines reacted with human sera of ATL patients and monoclonal antibodies against p19 and p24 of HTLV antigens. Cellular DNAs contained the provirus sequences homologous to HTLV-I by Southern blot hybridization. Moreover, they produced extracellular type-C virus particles and RNA-dependent DNA polymerase. All of these lymphoid line cells had Tac antigen, interleukin-2 receptor, and those of chimpanzee and red-faced macaque had helper/induced T-cell markers, while those derived from African green monkey had suppressor/cytotoxic T-cell markers. Furthermore, simian HTLV-related viruses of pig-tailed macaque, red-faced macaque and Japanese monkey were transmitted to human lymphocytes on co-cultivation.
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PMID:Isolation of simian retroviruses closely related to human T-cell leukemia virus by establishment of lymphoid cell lines from various non-human primates. 257 38

HUT-78 cells were infected with a reverse transcriptase (RT)-positive supernatant of a culture of peripheral blood lymphocytes (PBL) from an AIDS patient and then cloned. Of these clones, two have been isolated and characterized. Clone D10 is persistently and productively infected with an HIV variant. The clone F12, in spite of the presence of an integrated full-length HIV provirus, does not release virus particles in the medium. D10 and F12 clones substantially differ in terms of protein pattern; that is, D10 is super-imposable to infected HUT-78 cells, whereas F12 exhibits a decreased uncleaved p55 gag precursor and the presence of uncleaved gp160 and of a unique p19, although they do not show qualitative or quantitative differences in viral RNA synthesis. Restriction patterns of F12 proviral DNA do not show major genomic deletions. These results indicate that F12 clone cells carry an HIV genome with minor mutations that probably affect the correct production of viral proteins at a posttranscriptional level. In addition, the F12 clone is resistant to high-multiplicity superinfection with HIV-1 or HIV-2.
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PMID:Biologic and molecular characterization of producer and nonproducer clones from HUT-78 cells infected with a patient HIV isolate. 276 97

Human retroviruses have recently been linked with T cell lymphoproliferative disorders and with the acquired immune deficiency syndrome. We investigated the mechanisms for acquired pure red cell aplasia and cutaneous anergy in a patient with the chronic T gamma-lymphoproliferative disease (T gamma-LPD) syndrome. Patient marrow erythroid progenitors (BFU-E) were 17 +/- 9% of control and were selectively increased to 88-102% of control after marrow T cell depletion. Patient Leu 2+ suppressor T cells spontaneously produced high titers of human gamma-interferon and resulted in a concentration-dependent selective inhibition (74-91%) of BFU-E when co-cultured with autologous or allogeneic marrow. Conditioned media (CM) derived from patient Leu 2+ T cells similarly inhibited growth of autologous or allogeneic marrow BFU-E. The inhibitory factor derived from patient CM was acid-labile (pH 2) and sensitive to trypsin; prior treatment of patient T cells with anti-HLA-DR monoclonal antibody plus complement abrogated the suppressive effect of T cell-derived CM. Patient peripheral blood mononuclear cells (PBMC) were unable to support growth of cultured interleukin 2 (IL 2)-dependent T cells, but responded to exogenous IL 2 in vitro with a 16-21-fold augmentation, relative to control, in mitogen-induced proliferation. Antibodies to HTLV-I core proteins p19 and p24 but not to HTLV-III proteins were detected in patient serum by Western blotting; patient cultured PBMC stained (7-11%) with antibodies to p19 and p24. Patient cultured PBMC demonstrated integrated HTLV-I genomic sequences by the Southern technique and expressed both specific HTLV-I genomic sequences by RNA dot blot plus reverse transcriptase activity. Utilizing a cloned DNA probe for the beta chain of the T cell receptor gene, patient PMBC demonstrated gene rearrangements providing presumptive evidence for clonality. The presence in serum of HTLV-I p19 and p24 antibodies, the expression of p19 and p24 core antigens on patient mononuclear cells, the evidence of HTLV-I proviral integration sequences and the expression of HTLV-I genomic sequences in patient cells, indicates infection with HTLV-I and raises the possibility of an etiologic link between human retrovirus infection and some instances of large granular lymphocytic leukemia (T gamma-LPD).
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PMID:Human T cell leukemia virus-I-associated T-suppressor cell inhibition of erythropoiesis in a patient with pure red cell aplasia and chronic T gamma-lymphoproliferative disease. 289 60

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

Newly isolated strains of avian sarcoma virus, S1 and S2, were shown to have the transduced cellular src gene as their viral transforming gene (Yamagishi et al., Virology 137:266-275, 1984). In this work, the S1 and S2 genomes were molecularly cloned, and the junction sequences between the viral genomes and the c-src genes and the complete nucleotide sequences of the v-src genes transduced in these viruses were determined. Data on the junction sequences suggested that 5' recombination had occurred between the 5'-noncoding region of c-src and the 5' region of the gag sequence encoding p19 in both viruses and that 3' recombination had occurred in the last coding exon of c-src with either the middle portion of the env sequence encoding gp85 for S1 or the 3' portion of pol coding for reverse transcriptase for S2. Comparison of the amino acid sequences of the S1 and S2 src products deduced from the nucleotide sequences (pp62S1-src and pp62S2-src with that of c-src protein (pp60c-src) indicated that in pp62S1-src the 8 carboxy-terminal amino acid residues of the total of 533 in pp60c-src are replaced by 43 residues translated from the env sequence at the wrong frame. In pp62S2-src, on the other hand, the 14 carboxy-terminal amino acids of pp60c-src are replaced by the 38 carboxy-terminal residues of reverse transcriptase. The mechanism of c-src transduction and the structural changes necessary for pp60c-src activation are discussed.
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PMID:Activation of the cellular src gene by transducing retrovirus. 309 13

In this report, we describe a flow cytometric analysis of HTLV-I specific binding to fresh and cultured cells on a single cell basis. This assay uses rhodamine hydrocarbon tagged, purified HTLV-I virions according to the procedure originally described for avian retroviruses. Successful HTLV-I transmission was detected by analysis of integrated HTLV-I DNA, virion-associated reverse transcriptase, and/or intracellular HTLV-I core antigen p19 expression. Only a specific virus-cell interaction was detected because nonrhodamine-tagged homologous virus or related HTLV-II interfered with tagged HTLV-I binding. In contrast, an unrelated, nonlabeled animal retrovirus was unable to block tagged HTLV binding. Of the cell lines tested, 2 nonlymphoid mammalian and 3 human lymphoid bound significantly high to moderate levels of HTLV-I-tagged virions. The other three human lymphocyte cell lines were insensitive to HTLV-I adsorption. A direct correlation was observed between HTLV-I binding sites and infectivity of human lymphoid cells alone and not other nonlymphoid animal cells. Fresh normal human mononuclear cells bound low levels of HTLV-I virions. As expected, T lymphocytes demonstrated more binding than did the non-T cell population. Enhancement of HTLV-I cell binding in a subpopulation of mononuclear target cells was achieved with phytohemagglutinin (PHA) activation and interleukin 2 (IL2) stimulation, which correlates well with previously published infectivity studies.
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PMID:Specific adsorption of HTLV-I to various target human and animal cells. 349 86

The primary structure analysis of the gag gene products of human T-cell leukemia virus (HTLV)-ICR has been nearly completed. A comparison of the amino acid sequences with the published nucleotide sequence of HTLV-IATK established that i) p19 which is known to share antigenic determinants with a protein present in normal thymic epithelium, is nevertheless virally coded. ii) The gene order and complete primary structure of the gag precursor (Pr55) which has been shown to be myristylated (My) at its N-terminus is My-p19-p24-p15-OH; and iii) the Pr55gag amino acid sequences of HTLV-ICR and HTLV-IATK are nearly identical showing only a single residue difference in the C-terminal region of p15. Antibodies to synthetic peptides inferred from the nucleotide sequence of the env gene of HTLV-IATK were also raised and used to identify and purify env precursor gPr62-68, surface glycoprotein gp46-51 and transmembrane protein p21. While most of the peptide sera were shown to be subgroup specific some of them detected antigenic determinants shared between protein homologs of viruses of subgroups I and II. Partial or complete amino acid sequences of both the gag and env gene coded proteins of bovine leukemia virus (BLV) structural proteins have also been determined. These extensive protein data together with nucleotide sequences confirm and extend our initial finding that HTLV and BLV are structurally and antigenically related and may have originated from common ancestor. The structural and immunological studies revealed also relationships between HTLV and a number of type C and type D retroviruses studied. One of the highly conserved sequences is shared by the transmembrane proteins of these retroviruses which have been implicated in immunosuppression. It is conceivable that these common regions have common biological function. Two previously unidentified proteins of BLV have also been purified and structurally characterized. Nucleotide sequences capable of coding for related products are present in HTLV. The nature and possible biological functions of these new BLV proteins and the putative HTLV gene products will be discussed. The size and complexity of the genome of the replication competent retroviruses are similar but not identical. The 35S RNA of all replication competent helper viruses is divided into three genes encoding the viral structural proteins: the gag (group-specific antigen) gene codes for the internal structural proteins, the pol (polymerase) gene codes for the enzymes protease, reverse transcriptase and endonuclease and the env (envelope) gene codes for the proteins of the viral envelope.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Structural and antigenic characterization of the proteins of human T-cell leukemia viruses and their relationships to the gene products of other retroviruses. 610 Jun 35

A proteolytic activity is associated with structural protein p15 in avian RNA tumor viruses. Its effect on the known intracellular viral polyprotein precursors obtained by immunoprecipitation was investigated. Cleavage of Pr76gag resulted in the sequential appearance of p15, p27, and p19. The intracellular precursor Pr180gag-pol was also cleaved by p15, whereas the intracellular glycoprotein precursors of avian RNA tumor viruses, Pr92env, remained unaffected by p15 under all conditions tested. The specificities of the antibodies used to precipitate the precursors influenced the pattern of intermediates and cleavage products obtained by p15 treatment. If virus harvested from the the Prague strain of Rous sarcoma virus, subgroup C-transformed cells at 15-min intervals was incubated at 37 degrees C for further maturation, RNA-dependent DNA polymerase activity showed an optimum of DNA synthesis with 70S viral RNA or synthetic template-primers after short incubation periods. The presence of additional p15 during incubation resulted in a shift of the enzyme activity peak toward earlier time points. Virus harvested at 3-h intervals contained significant amounts of Pr180gag-pol and Pr76gag. The addition of p15 resulted in the cleavage of Pr180gag-pol and Pr76gag, but only a few distinct low-molecular-weight polypeptides appeared. Treatment of purified RNA-dependent DNA polymerase with p15 in vitro resulted in a disappearance of the beta subunit and an enrichment of the alpha subunit. In addition, a polypeptide of 32 x 10(3) molecular weight was generated. The cleavage pattern observed differed from the one obtained by trypsin treatment.
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PMID:Effect of p15-associated protease from an avian RNA tumor virus on avian virus-specific polyprotein precursors. 615 35

We have previously shown that the inhibition of methylation reactions by the treatment of B77 avian sarcoma virus-infected cells with medium containing cycloleucine results in an inhibition in the intracellular accumulation of the spliced subgenomic mRNA for the virion envelope protein precursor, whereas the genome-size RNA accumulates in larger than normal amounts (C. M. Stoltzfus and R. W. Dane, J. Virol. 42:918-931, 1982). To measure the production of virus particles, we have now determined the reverse transcriptase activity in the culture fluid from infected cells treated with various concentrations of cycloleucine. The activity was somewhat greater in the fluid from the cycloleucine-treated cells than it was in the fluid from the control cells, suggesting an enhancement of particle production in the presence of cycloleucine. In contrast, the production of infectious virions, as determined by the focus assay, decreased when the cycloleucine concentration of the medium increased. We determined the polypeptide compositions of purified particles produced from infected cells treated with or without cycloleucine and labeled with [(3)H]leucine. The relative amounts of radioactivity associated with p19 and p27 were approximately the same in all of the preparations. In contrast, significant decreases were observed in the relative amounts of [(3)H]leucine radioactivity associated with the virion glycoproteins gp85 and gp37. The extent of the decrease in the ratio of gp85 to p27 was a function of the cycloleucine concentration and correlated well with the decrease in the infectivity of the virus particles. Therefore, it is probable that the observed reduction of specific infectivity results from the reduced amounts of envelope glycoproteins in the particles budding from cycloleucine-treated cells.
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PMID:Particles of reduced infectivity and deficient in envelope glycoproteins are produced in cycloleucine-treated B77 avian sarcoma virus-infected chicken embryo fibroblasts. 618 42

Sera and peripheral blood cells of an adult T-cell leukemia patient and several clinically normal members of his family from the northwest coast of Japan were examined for evidence of infection with human T-cell leukemia (lymphoma) virus (HTLV). The sera of the patient and his parents had antibodies to HTLV, whereas these antibodies were absent in the sera of the patient's brother and sister. T-cell lines were established from the peripheral blood lymphocytes of all of the family members, and all except the patient's sister expressed HTLV antigens (p19, p24, and reverse transcriptase) and type-C virus particles. Not only the fresh peripheral blood lymphocytes from the patient but also those from his clinically normal mother showed abnormal morphology of the kind characteristic of some patients with T-cell leukemia. These studies are consistent with previous evidence indicative of a high rate of HTLV infection within families, and they show that people whose sera are negative for antibodies may still be infected by HTLV. In addition, the results indicate that infection of T cells by HTLV can be associated with morphological transformation of the cells without other signs of leukemia.
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PMID:High incidence of human type-C retrovirus (HTLV) in family members of a HTLV-positive Japanese T-cell leukemia patient. 630 Sep 13


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