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)

Cells doubly infected with two mutants of the Schmidt-Ruppin strain of Rous sarcoma virus (RSV), ts68, which is temperature sensitive for cell transformation (srcts), and a deletion mutant, N8, which is deficient in the envelope glycoprotein (env-), produced a recombinant which carried the defects of both parents. The frequency of formation of such a recombinant was exceptionally high and made up 45 to 55% of the progeny carrying the srcts marker. By contrast, the reciprocal recombinant, which is wild type in transformation (srcts) and contains the subgroup A envelope glycoprotein (envA), was almost undetectable. This remarkable difference in the frequency of the formation of the two possible recombinants suggests that a unique mechanism may be involved in the genetic interaction of the two virus genomes, one of which has a large deletion. When an RNA-dependent DNA polymerase-negative variant of the N8 (N8alpha) was crinants also became deficient in the polymerase. Cells infected by the srctsenv- recombinant were morphologically normal at the nonpermissive temperature (41 degrees C) and susceptible to all subgroups of RSV. The rate by which the wild-type RSV transformed the recombinant-preinfected cells was indistinguishable from that of transformation of uninfected chicken cells by the same wild-type virus. This indicates that no detectable interference exists at postpenetration stages between the preinfected and superinfecting virus genomes and confirms that the expression of the transformed state is dominant over the suppressed state.
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PMID:Recombination between a temperature-sensitive mutant and a deletion mutant of Rous sarcoma virus. 6 Apr 96

From the same batch of virus, the four major avian viral structural proteins p27, p19, p15, and p12, the reverse transcriptase, the envelope glycoprotein gp85, and the high molecular weight 70 S RNA have been recovered. All proteins, except for gp85, have been purified by use of column chromatography procedures to apparent homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gels and isoelectric focusing. A new isolation procedure for p12 by affinity column chromatography takes advantage of its nucleic acid binding properties. The recovery of nondenatured viral structural proteins is demonstrated by the proteolytic activity revealed by p15. The purified proteins were used for the production of monospecific antibodies. The 70 S RNA served as source for the isolation of 35 S RNA subunits.
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PMID:The isolation of avian viral RNA and polypeptides. 8 39

Strains of Friend leukemia virus (FLV) that are associated with polycythemia contain the defective spleen focus-forming virus (SFFV). To determine whether the transforming ability of FLV was affected by the presence of this second agent, DBA/2J mouse bone marrow cells were infected in vitro. Criteria for transformation were the establishment of permanent lines, growth on semisolid agarose, and the production of tumors at the site of inoculation in syngeneic hosts. Two lines of immature hematopoietic cells that grow in suspension originated from the infected cultures. Each has an almost diploid karyotype (38-39 chromosomes) and 3-4 metacentric chromosomes. These transformed cells express gp71 viral envelope glycoprotein and p30 viral core protein antigens. Virus production was measured by reverse transcriptase (RNA-dependent DNA polymerase) activity of the virions released into the medium. The virus, assayed in vivo for infectivity, has SFFV activity but is attenuated for leukemogenicity. The stimulation of hemoglobin synthesis in the cells grown in medium supplemented with dimethyl sulfoxide or hexamethylene bisacetamide indicates that the cells are erythroid in origin. SFFV may have a function analogous to erythropoietin in influencing the process of transformation by FLV.
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PMID:In vitro transformation of mouse bone marrow cells by the polycythemic strain of Friend leukemia virus. 8 91

Extracts from lymphoid and fibroblast cell lines transformed by Abelson murine leukemia virus (A-MuLV) contain a protein of molecular weight 120,000 (P120). Immunoprecipitation with specific sera shows that P120 contains regions homologous to the 5'-terminal segment of the MULV gag gene complex--p15, p12, and at least part of p30--but lacks detectable determinants of p10, reverse transcriptase, and the envelope glycoprotein. P120 is phosphorylated and has an intracellular half-life of 3--6 hr. In vitro translation of virion RNA from A-MuLV, with Moloney MuLV as helper, yields a product of molecular weight 120,000 with serological reactivity similar to that of the cellular P120. Translation of the RNA from the helper gave no P120. P120 is expressed in all lymphoid and fibroblastic cell lines we have tested that were transformed by A-MuLV but is not detectable in a lymphoid line in which the A-MuLV genome was established by infection but was not responsible for the transformation. Expression of P120 is selectively retained in clones of A-MuLV-transformed lymphocytes that convert to a nonproducer state after loss of expression of helper MuLV intracellular precursors. These results suggest that the P120 product of the A-MuLV genome may be responsible for maintenance of the transformed phenotype of lymphoid and fibroblast cells transformed by the virus.
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PMID:Identification of an Abelson murine leukemia virus-encoded protein present in transformed fibroblast and lymphoid cells. 20 68

Cell clones nonproductively transformed by the replication-defective Abelson strain of murine leukemia virus (AbLV) were analyzed for type C viral antigen expression by competition immunoassay. AbLV-transformed mink non-producer lines were found to express a 110,000- to 130,000-molecular weight polyprotein containing murine leukemia virus gag proteins p15 and p12 covalently linked to nonstructural AbLV-coded component(s) of around 80,000-100,000 molecular weight. This polyprotein lacked detectable antigenic cross-reactivity with other virion-coded gag gene proteins such as p30, p10, the viral reverse transcriptase (RNA-dependent DNA polymerase), or the major viral envelope glycoprotein, gp70. By analogy to earlier data on feline and avian sarcoma viruses, these results suggest that a portion of this polyprotein might represent the AbLV src gene product and that in translation it is initially linked in precursor form to gag structural proteins. Superinfection of mink cells nonproductively transformed by AbLV--with either a wild mouse amphotropic type C virus isolate, 4070-A, or with the endogenous cat virus, RD114--led to production of pseudotype virus containing high concentrations of the AbLV-coded precursor polyprotein.
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PMID:Cells nonproductively transformed by Abelson murine leukemia virus express a high molecular weight polyprotein containing structural and nonstructural components. 21 10

Tumours induced in chickens by inoculation of avian sarcoma viruses are frequently capable of undergoing spontaneous regression. It is only those tumour cells which have been derived from progressively growing neoplasms that are able to produce transforming progeny virus in vitro and to shed into the culture medium antigens which are specifically reactive with the peripheral lymphocytes of sarcoma-bearing hosts. Following multiple passages and extended growth in culture, however, the ability of these tumour cell fluids to stimulate the lymphocytes of sensitized hosts diminishes in concert with the declining capacity of these cells to continue to synthesize fully transforming progeny virus. In certain instances, however, aged tumour cells are able to synthesize particles which contain the enzyme RNA-dependent DNA polymerase yet lack detectable envelope glycoprotein.
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PMID:Decreased production of transforming virus and altered antigenic behaviour in cultured avian sarcoma cells. 21 55

Levels of human immunodeficiency virus (HIV) DNA, RNA, or p24 antigen and reverse transcriptase activity in T-cell cultures treated with 500 IU of recombinant alpha interferon (rIFN alpha) per ml were comparable to those in control cultures. Radioimmunoprecipitation analysis of proteins in lysates of IFN-treated T cells documented a marked accumulation of HIV proteins. Localization of gp120 by immunofluorescence showed a diffuse pattern in IFN-treated cells quite distinct from the ring pattern in untreated control cells. That large quantities of gp120 in aberrant cell compartments might affect HIV morphogenesis was confirmed in infectivity studies: virions from IFN-treated cells were 100- to 1,000-fold less infectious than an equal number of virions from control cells. Direct examination of IFN-treated and control HIV-infected cells by transmission electron microscopy showed little difference in the number or distribution of viral particles. However, quantitation of gp120 by immunogold particle analysis revealed a marked depletion of envelope glycoprotein in virions released from IFN-treated cells. This defect in gp120 assembly onto mature viral particles provides a molecular basis for this loss of infectivity.
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PMID:Loss of infectivity by progeny virus from alpha interferon-treated human immunodeficiency virus type 1-infected T cells is associated with defective assembly of envelope gp120. 127 6

Various polyoxometalates proved inhibitory to the replication of a number of enveloped DNA and RNA viruses, i.e., herpesviruses (herpes simplex and cytomegalo), togaviruses (Sindbis), paramyxoviruses (respiratory syncytial), rhabdoviruses (vesicular stomatitis), arenaviruses (Junin and Tacaribe), and retroviruses [human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), simian immunodeficiency virus, and murine sarcoma virus]. The most potent compounds, i.e., JM1590 [K13[Ce(SiW11O39)2]. 26H2O] and JM2766 [K6[BGa(H2O)W11O39]. 15H2O], inhibited HIV-1 and simian immunodeficiency virus at concentrations as low as 0.008-0.8 microM. The polyoxometalates also inhibited giant cell formation in co-cultures of HIV-infected HUT-78 cells and uninfected MOLT-4 cells. Studies designed to unravel the mechanism of action of these compounds revealed that they inhibit the reverse transcriptase activity associated with HIV. The polyoxometalates also proved inhibitory to the binding of HIV-1 virions to the cells. From "time of addition" experiments, whereby the polyoxometalates were added at different times after virus infection, their mechanism of anti-HIV action could be attributed to inhibition of virus-cell binding. There was a good correlation (r = 0.84) between the inhibitory effects of the compounds on HIV-1-induced cytopathicity and their inhibitory effects on syncytium formation and a close correlation (r = 0.902) between their inhibitory effects on syncytium formation and their interaction with gp120, whereas there was no correlation between their anti-HIV-1 activity and their inhibitory effects on HIV-1 reverse transcriptase. In flow cytometric studies, the compounds did not interfere with the binding of OKT4A/Leu-3a monoclonal antibody to the CD4 receptor of uninfected cells, but they inhibited binding of anti-gp120 monoclonal antibody to HIV-1-infected cells. Thus, the binding of the polyoxometalates to the viral envelope glycoprotein gp120 is responsible for their anti-HIV activity.
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PMID:Mechanism of anti-human immunodeficiency virus action of polyoxometalates, a class of broad-spectrum antiviral agents. 128 64

The role of the N-linked glycosylation sites in the major envelope glycoprotein, SU (gp70), of Moloney murine leukemia virus has been examined. By using site-specific oligonucleotide-directed mutagenesis, each of the seven glycan addition sites has been individually eliminated. Mutations resulting in the loss of a single glycosylation site produced, intracellularly, stable precursor SU-TM proteins which were 4 to 5 kDa smaller than the wild-type virus SU-TM protein. Mutant delta 1,4,7, a trimutant lacking three N-linked glycan addition sites, resulted in a viable, infectious virus with a stable SU-TM protein approximately 12 to 15 kDa smaller than the wild-type SU-TM protein. Five of the seven single-site mutations resulted in viable virus as judged by the release of reverse transcriptase in transient-expression assays and XC syncytium assays. Mutations at two of the sites resulted in a detectable phenotype. Virus mutated at position 2 was temperature sensitive in Rat2 cells; viable virus was produced at 32 degrees C but not at 37 degrees C. Virus mutated at position 3 was noninfectious and yielded virions lacking detectable mature SU protein. The mutation results in the block of transport of the protein to the cell surface and assembly into virion particles.
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PMID:Mutational analysis of the N-linked glycosylation sites of the SU envelope protein of Moloney murine leukemia virus. 131 4

Little is known about the relationship between recovery from acute viral encephalitis and the clearance of viral genetic material from the central nervous system. In a mouse model of Sindbis virus encephalitis, we have previously shown that clearance of infectious virus is mediated by antibody-induced restriction of viral gene expression rather than by cytotoxic destruction of virally infected cells. To explore whether Sindbis virus genomes persist in mouse brain after the clearance of infectious virus, we used reverse transcriptase-polymerase chain reaction amplification methods to detect Sindbis virus RNA in brain samples from immunocompetent BALB/c and antibody-treated immunodeficient scid/CB17 mice. RNA sequences from both the nonstructural region (NSP1 gene) and structural regions (E2 gene) of Sindbis virus were detected in the brains of all BALB/c and antibody-treated scid mice examined at 1, 2, and 3 months after infection. Additional BALB/c mouse brains were also positive at 8, 12, and 17 months after infection. To determine whether persistent RNA was capable of resuming unrestricted replication in the absence of the continuous presence of antiviral antibodies, viral titers were measured in the brains of scid mice at 1, 2, 3, and 6 months after antibody treatment. Viral reactivation was seen in scid mice treated with hyperimmune serum or a low dose of monoclonal antibody to the E2 envelope glycoprotein, but not in mice treated with a high dose of monoclonal antibody to E2. Replication of infectious virus isolated from scid mouse brain could be restricted by repeat treatment with immune serum, indicating that viral reactivation is not due to antibody-escape mutations. These results demonstrate that Sindbis virus can persist long term in a nonproductive form in mouse brain and suggest that the humoral immune response plays an important role in preventing viral reactivation.
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PMID:Persistence of viral RNA in mouse brains after recovery from acute alphavirus encephalitis. 138 64


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