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S G Devare

Publications and source records attributed to S G Devare.

At least 55 records · Page 3Linked to original sources
PubMed1982

In vivo identification of the transforming gene product of simian sarcoma virus.

Simian sarcoma virus (SSV) deletion mutants were constructed from a molecular clone containing the entire infectious provirus. Transfection analysis of these mutants localized the SSV transforming gene to a small region of the viral genome encompassing its cell-derived sequence (v-sis). Antiserum to a peptide synthesized on the basis of the predicted amino acid sequence of the SSV transforming gene detected a 28,000-dalton protein that was specifically expressed in SSV transformed cells and that corresponded in size to that predicted from the v-sis coding sequence. The v-sis gene product designated p28sis was not a phosphoprotein, nor did it possess detectable protein kinase activity. These findings distinguish p28sis from a number of other retroviral onc proteins.

Animals↗
PubMed1982

Nucleotide sequence of the transforming gene of simian sarcoma virus.

The sequence of the transforming region of simian sarcoma virus (SSV) has been determined by using molecularly cloned viral DNA. This region encompassed the 1.0-kilobase pair woolly monkey cell-derived insertion sequence, v-sis, and flanking simian sarcoma-associated viral (SSAV) sequences. A 675-nucleotide-long open reading frame commenced 19 nucleotides within the SSAV sequences to the left of the v-sis helper viral junction and terminated within v-sis itself. Possible promoter and acceptor splice signals were detected in helper viral sequences upstream from this open reading frame, and potential polyadenylylation sites were identified downstream both within v-sis and in helper viral sequences beyond v-sis. The recombinational event that led to the generation of SSV occurred in the middle of two functional codons, indicating that SSAV provided the regulatory elements for transcription as well as the initiation codon for translation of SSV cell-derived transforming sequences.

Cell Transformation, Viral↗
PubMed1982

Molecular cloning and chromosomal mapping of a human locus related to the transforming gene of Moloney murine sarcoma virus.

Human DNA was analyzed for the presence of sequences homologous to the transforming gene (v-mos) of Moloney murine sarcoma virus. A single 2.5-kilobase pair (kbp) EcoRI-generated fragment of human DNA was identified by using cloned v-mos as probe. This DNA was molecularly cloned in a bacteriophage vector. By heteroduplex and restriction enzyme analyses, this human DNA fragment, designated c-mos (human), contained a 0.65-kbp region of continuous homology with v-mos and was present as a single copy in human DNA. By testing for the presence of c-mos (human) in somatic cell hybrids possessing various numbers of human chromosomes, as well as in subclones of such hybrids, it was possible to assign c-mos (human) to human chromosome 8.

Base Sequence↗
PubMed1982

Abelson murine leukemia virus: structural requirements for transforming gene function.

The integrated Abelson murine leukemia virus (A-MuLV) genome cloned in bacteriophage lambda gtWES.lambda B was used to localize viral genetic sequences required for transformation. Comparison of the biological activity of cloned A-MuLV genomic and subgenomic fragments showed that subgenomic clones that lacked the 5' long terminal repeat and adjoining sequences (300 base pairs downstream of the repeat) were not biologically active. In contrast, subgenomic clones that lacked the 3' long terminal repeat and as much as 1.3 kilobase pairs of the A-MuLV cell-derived abl gene were as efficient as wild-type viral DNA in transformation. The A-MuLV-encoded polyprotein P120 and its associated protein kinase activity were detected in transformants obtained by transfection with Cla I, BamHI, and HindIII subgenomic clones. In contrast, individual transformants obtained with subgenomic Sal I clones expressed A-MuLV proteins ranging in size from 82,000 to 95,000 daltons. Each demonstrated an associated protein kinase activity. These results provide direct genetic evidence that only the proximal 40% of abl with its associated 5' helper viral sequences is required for fibroblast transformation.

Abelson murine leukemia virus↗
PubMed1982

Nucleotide sequence analysis of the long terminal repeat of integrated simian sarcoma virus: evolutionary relationship with other mammalian retroviral long terminal repeats.

Nucleotide sequence analysis of the long terminal repeat (LTR) of the integrated simian sarcoma virus showed that the simian sarcoma virus LTR comprised 504 nucleotides with an inverted repeat of seven bases at its 5' and 3' termini. At the site of simian sarcoma virus integration, cellular flanking sequences adjacent to the proviral LTR contained a direct repeat of four bases. A 13-base sequence after the 5' LTR was found to be complementary to prolyl tRNA, suggesting that tRNAPro may serve as the primer for reverse transcription of simian sarcoma virus RNA. The U5 and R regions, derived respectively from the 5' end and terminally redundant sequences of the viral RNA, were found to have similar organization and sequence homology close to that of Moloney murine sarcoma virus or Moloney murine leukemia virus. These results indicate that regions within LTRs with known functionally important sequences have been most well conserved during retrovirus evolution.

Biological Evolution↗
PubMed1981

Generation of BALB-MuSV and Ha-MuSC by type C virus transduction of homologous transforming genes from different species.

The nature of the cell-derived (bas) sequences of BALB-MuSV, a spontaneous mouse sarcoma virus isolate, was determined. Molecularly cloned bas sequences demonstrated no detectable homology with the onc genes of other mouse transforming viruses, but exhibited a high degree of sequence homology with the ras gene of the rat-derived Harvey murine sarcoma virus (Ha-MuSV) genome. The Ha-MuSV cell-derived sequence (ras) shared a colinear 750 bp region of homology with bas. Moreover, BALB-MuSV transformation was associated with the expression of high levels of a 21,000 dalton protein, immunologically related to the ras gene products, p21. Thus bas and ras represent retroviral transforming gene homologs that were independently transduced by mouse type C viruses from the genomes of different species.

Abelson murine leukemia virus↗
PubMed1981

Molecular cloning of integrated simian sarcoma virus: genome organization of infectious DNA clones.

The integrated form of simian sarcoma virus (SSV) was molecularly cloned in the Charon 16A strain of bacteriophage lambda. In transfection analysis, the recombinant viral DNAs demonstrated the ability to transform cells in tissue culture at high efficiency. Such transformants possessed typical SSV morphology, expressed simian sarcoma associated virus (SSAV) gag gene products in the absence of virus release, and released SSV after superinfection with a type C helper virus. A physical map of the 5.8-kilobase-pair (kbp) recombinant viral DNA clone, deduced from restriction endonuclease analysis, revealed a 5.1-kbp SSV genome containing 0.55-kbp-long terminal repeats flanked by 0.45 and 0.25 kbp of contiguous host cell sequences. By R-loop analysis, the viral DNA molecule contained two regions of homology to SSAV, separated by a 1.0-kbp nonhomologous region. This SSV-specific sequence was shown to be uniquely represented within the normal cellular DNA of diverse mammalian species, including human. Our results demonstrate that this primate transforming retrovirus arose in nature by recombination of a type C helper virus and a host cellular gene.

Animals↗
PubMed1980

Origin and functional properties of the major gene product of the Snyder-Theilen strain of feline sarcoma virus.

The only known product of the Snyder-Theilen strain of feline sarcoma virus (ST-FeSV) is a 85,000-dalton protein, designated ST P85, that contains feline leukemia virus gag gene encoded proteins (p15, p12, and a fragment of p30) and a sarcoma virus-specific polypeptide. Antibodies directed against the latter immunoprecipitated a 92,000-dalton phosphoprotein (NCP 92) expressed at low levels in normal feline embryo fibroblasts as well as in feline cells of epithelial or lymphoid origin. Normal cellular proteins crossreactive with ST P85 were also detected in cell lines from various other mammalian species. These results suggest that the ST-FeSV sequences encoding for the sarcoma virus-specific domain of ST P85 originated from an evolutionarily conserved cellular gene expressed in cells of independent differentiation lineage. Immunoprecipitates containing ST-FeSV P85 exhibited a protein kinase activity that specifically phosphorylated tyrosine residues. The physiological significance of this finding is illustrated by the finding that phosphotyrosine is an intrinsic component of ST P85. Furthermore, 5- to-fold higher levels of this unusual phosphorylated amino acid were present in ST-FeSV transformants than in uninfected control cells. Phosphorylation of tyrosine residues appears to be associated with cellular transformation caused by Rous sarcoma virus and Abelson murine leukemia virus. Thus, independent transforming virus isolates from birds, mice, and cats may utilize common pathways in exerting their oncogenic potential.

Animals↗
PubMed1980

Biochemical and immunological characterization of polyproteins coded for by the McDonough, Gardner-Arnstein, and Snyder-Theilen strains of feline sarcoma virus.

The McDonough (SM), Gardner-Arnstein (GA), and Snyder-Theilen (ST) strains of feline sarcoma virus (FeSV) code for high-molecular-weight polyproteins that contain varying amounts of the amino-terminal region of the FeLV gag gene-coded precursor protein and a polypeptide(s) of an as yet undetermined nature. The SM-FeSV primary translational product is a 180,000-dalton polyprotein which is immediately processed into a highly unstable 60,000-dalton molecule containing the p15-p12-p30 fragment of the FeLV gag gene-coded precursor protein and a 120,000-dalton FeSV-specific polypeptide. The GA- and ST-FeSV genomes code for polyproteins of 95,000 and 85,000 daltons, respectively, which in addition to the amino-terminal moiety (p15-12 and a portion of p30) of the FeLV gag gene-coded precursor protein also contain FeSV-specific polypeptides. However, the GA- and ST-FeSV polyproteins appear to be relatively stable molecules (half-lives of around 16 h) and are not significantly processed into smaller polypeptides. Immunological and biochemical analysis of each of the above FeSV translational products revealed that the sarcoma-specific regions of the GA- and ST-FeSV polyproteins are antigenically cross-reactive and exhibit common methionine-containing peptides. These findings favor the concept that these sarcoma-specific polypeptides are coded for by the similar subsets of cellular sequences incorporated into the GA- and ST-FeSV genomes during the generation of these transforming agents.

Animals↗
PubMed1979

Molecular cloning of Moloney murine sarcoma virus: arrangement of virus-related sequences within the normal mouse genome.

The unintegrated circular DNA form of Moloney murine sarcoma virus (MSV) has been cloned in bacteriophage lambda. Discrete deletions in the viral genome were shown to occur during propagation of recombinant phage in Escherichia coli. Heteroduplex and restriction enzyme analyses indicated the deletion of tandemly repeated sequences within certain of the cloned MSV DNA inserts. Cloned MSV DNA was used to prepare a probe composed of its acquired cellular (src) sequences, shown previously to be necessary for MSV transformation. Analysis of EcoRI digests of normal mouse cellular DNA revealed the presence of a single 14-kilobase-pair fragment containing these sequences which lacked contiguity with endogenous type C helper viral information of the same cells. Thus, the sarcoma virus-specific sequences of MSV are represented within the normal mouse genome in a manner analogous to that of a cellular gene.

Animals↗
PubMed1979

Primate retroviruses: intracistronic mapping of type D viral gag gene by use of nonconditional replication mutants.

Nonconditional replication mutants of squirrel monkey retrovirus (SMRV), an endogenous type D virus of primates, are shown to be defective in post-translational processing of nonglycosylated virus-coded structural proteins. Utilizing such mutants, in combination with sensitive radioimmunological assays, we demonstrate the existence of a 72,000-molecular-weight precursor polyprotein (Pr72gag) encoded by a region of the SMRV genome designated gag. Post-translational cleavage of this precursor polyprotein gives rise to virion structural proteins of 35,000 (p35), 16,000 (p16), 12,000 (p12), and 9,000 (p9) molecular weight. Three of these viral proteins, p35, p16, and p9, are shown to be phosphorylated. Analysis of viral antigen expression in cell lines nonproductively infected with either of two replication-defective SMRV mutants or mink cells productively infected with wild-type SMRV resulted in the detection of several SMRV Pr72gag intermediate cleavage products. Adjacent proteins within such intermediates are identified by use of specific competition immunoassays, and the intracistropic order of individual structural proteins with SMRV Pr72gag was tentatively deduced as NH2-p16-p12-p35-p9-COOH.

Animals↗
PubMed1978

Primate retroviruses: immunological cross-reactivity between major structural proteins of new and old world primate virus isolates.

The major 35,000-molecular-weight internal antigen (p35) of the squirrel monkey retrovirus (SMRV) was isolated and partially characterized. Immunological analysis of SMRV p35 led to the demonstration of antigenic determinants common to SMRV and the Mason-Pfizer monkey virus (MPMV). A broadly reactive competition immunoassay was developed utilizing antiserum to MPMV to precipitate 125I-labeled SMRV p35. Although the major structural proteins of MPMV and SMRV competed with equal efficiency in this assay, type B and type C oncornavirus proteins lacked detectable reactivity. Antibodies reactive with the major structural proteins of both MPMV and SMRV were observed in sera of several normal rhesus monkeys with known prior exposure to MPMV-infected animals. These findings demonstrate the ability of sera from naturally immunized primates to recognize broadly reactive interspecies antigenic determinants shared by the major structural proteins of type D oncornaviruses, and they suggest possible horizontal transmission of MPMV among rhesus monkeys. Although sera from a number of squirrel monkeys contained antibody to SMRV p35, the possibility that this latter reactivity was due to endogenous virus activation rather than horizontal transmission cannot be ruled out.

Animals↗
PubMed1978

Primate retroviruses: envelope glycoproteins of endogenous type C and type D viruses possess common interspecies antigenic determinants.

The major 70,000- to 80,000-molecular-weight envelope glycoproteins of the squirrel monkey retrovirus, Mason-Pfizer monkey virus, and M7 baboon virus and the related endogenous feline virus, RD114, were isolated and immunologically characterized. Immunoprecipitation and competition immunoassay analysis revealed these viral envelope glycoproteins to possess several distinct classes of immunological determinants. These include species-specific determinants, group-specific antigenic determinants unique to endogenous primate type C viruses, and group-specific determinants for type D viruses such as Mason-Pfizer monkey virus and squirrel monkey retrovirus. In addition, a class of broadly reactive antigenic determinants shared by envelope glycoproteins of both type C viruses of the baboon/RD114 group and type D viruses of the Mason-Pfizer monkey virus/squirrel monkey virus group are described. Other mammalian oncornaviruses tested, including isolates of nonprimate origin and representative type B viruses, lacked these determinants. The demonstration of antigenic determinants specific to envelope glycoproteins of type C and type D primate viruses indicates either that these viruses are evolutionarily related or that genetic recombination occurred between their progenitors. Alternatively, endogenous type D oncornaviruses may be replication defective, and acquisition of endogenous type C viral genetic sequences coding for envelope glycoprotein determinants may be necessary for their isolation as infectious virus.

Animals↗
PubMed1978

Acquisition of oncogenicity by endogenous mouse type C viruses: effects of variations in env and gag genes.

Several dual-tropic isolates derived from the thymuses of preleukemic or leukemic AKR mice and a more recrnt group of viruses generated by in vitro or in vivo passage of a poorly infectious endogenous virus of C3H mouse cells have been shown to be highly oncogenic. By analysis of the immunological properties of their gag gene-coded structural proteins, each of the AKR-derived isolates and two dual-tropic C3H-derived isolates were found to closely resemble AKR murine leukemia virus. In contrast, gag gene-coded proteins of two other leukemogenic isolates of C3H origin, including one ecotropic and one dual-tropic virus, were indistinguishable from those of Moloney murine leukemia virus. All of the oncogenic isolates, including those of AKR and C3H origin, were found to possess common envelope glycoprotein determinants of a unique class not shared by the nononcogenic ecotropic viruses from which they were derived. These findings support the possibility that oncogenic variants of endogenous ecotropic mouse type C viruses are derived by genetic recombination. This recombinational event appears to involve the acquisition, by different ecotropic viruses, of a common class of endogenous virus-coded envelope glycoprotein determinants which are presumably required, but not necessarily sufficient, for oncogenicity.

AKR murine leukemia virus↗