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Biomedical subjects

R Callahan

Publications and source records attributed to R Callahan.

At least 127 records · Page 7Linked to original sources
PubMed1984

Major pol gene progenitors in the evolution of oncoviruses.

The genetic relationships among molecularly cloned prototype viruses representing all of the major oncovirus genera were investigated by molecular hybridization and nucleotide sequence analysis. One of the major progenitors of the pol genes of such viruses gives rise to mammalian type C viruses and another gives rise to type A, B, D, and avian type C oncoviruses. Evidence of unusual patterns of homology among the env genes of mammalian type C and D oncoviruses illustrates that genetic interactions between their progenitors contributed to the evolution of oncoviruses.

Amino Acid Sequence↗
PubMed1982

Novel class of mouse mammary tumor virus-related DNA sequences found in all species of Mus, including mice lacking the virus proviral genome.

Mice in breeding colonies of feral Mus musculus brevirostris (Azrou, Morocco), M. m. musculus (Studenec, Czechoslovakia), and M. m. molossinus (Fukuoka, Japan) were found to lack the mouse mammary tumor virus (MMTV-alpha) proviral genome in their germ line. MMTV-alpha proviral genomes have been found in all inbred strains of M. musculus by using high-stringency nucleic acid hybridization conditions. We conclude that feral mice in these colonies are heterozygous for a limited number of MMTV-alpha proviral genomes and that those lacking them arose as a result of random chromosomal segregation. All mice in another breeding colony of feral M. m. musculus (Sladeckovce, Czechoslovakia) lack MMTV proviral genes. By relaxing the conditions of nucleic acid hybridization, MMTV-related sequences (designated MMTV-beta) were detected in restricted cellular DNA from MMTV-negative mice and all other inbred strains and feral species of the genus Mus. The apparent ubiquity of the MMTV-beta DNA sequences in the genus Mus and the lack of variation in the pattern of restriction fragments containing these sequences within a species distinguishes them from MMTV-alpha. These results suggest that the MMTV-beta DNA sequences either are the evolutionary progenitors of the infectious MMTV genome or represent an accumulation of evolutionarily divergent MMTV-alpha insertions into the mouse germ line.

Animals↗
PubMed1982

Detection and cloning of human DNA sequences related to the mouse mammary tumor virus genome.

Sequences related to the mouse mammary tumor virus (MMTV) genome have been detected in fragments of restricted human cellular DNA. These results were obtained by using recombinant DNA containing the MMTV proviral genome and lowering the stringency of blot-hybridization conditions. The MMTV genome also reacts with unique families of fragments in restricted cellular DNA from other mammalian species but not with salmon sperm DNA. A clone that reacted with labeled MMTV proviral DNA was selected from a human DNA library in Charon 4A. Under stringent conditions, a 3.7-kilobase MMTV-related EcoRI fragment of this clone hybridized with many of the same EcoRI restriction fragments of human cellular DNA detectable with MMTV proviral DNA under low-stringency conditions. Specific fragments of the human clone were shown to contain sequences related to the molecularly cloned gag, pol, and env regions of the MMTV genome.

Base Sequence↗
PubMed1981

Genetic relationship between the Mus cervicolor M432 retrovirus and the Mus Musculus intracisternal type A particle.

The genetic relationship between the retrovirus-like intracisternal type A particle (IAP) from Mus musculus and the novel retrovirus (M432) from M. cervicolor has been determined by heteroduplex and restriction endonuclease analyses of molecular clones of the respective genomes. We have found a major homology region (3.7 kilobase pairs) which probably begins near the 3' end of the M432 gag gene, spans the pol gene, and ends in the env gene. A second region (0.6 kilobase pairs) of weak homology was also observed adjacent to the 3' long terminal repeats of the respective genomes. The IAP genome is well conserved in the cellular DNA of all species of the genus Mus. In contrast, cellular DNA sequences related to the 5' end of the M432 genome, which shares no homology with the IAP genome, are found only in M. cervicolor and the closely related species M. cookii. These results suggest that the infectious M432 retroviral genome arose as a result of a recombinational event(s) between the IAP genome and another, as yet unidentified, class of retrovirus-related sequences or other cellular sequences.

Animals↗
PubMed1980

Genetic transmission of retroviral genes and cellular oncogenes.

Several different families of retrovirus genome have been found to exist, each in multiple copies, in the cellular DNA of rodents and primates. There are at least four distinct families of genome in rodents: two type C families, the MTV family and another related to mouse type A particles. In primates there are also at least two families of endogenous type C virogenes and a third type D virogene family. Both in rodents and in primates, the virus-related sequences constitute almost 0.1% of the cellular genome. We have been able to generate transforming viruses, starting with endogenous mouse 'helper' type C viruses by passing them through chemically transformed mouse cells and selecting for variant viruses that have acquired the ability to induce normal cells to display anchorage-independent growth. These viruses produce both sarcomas and carcinomas in the animal; clones that produce only pulmonary carcinomas have also been selected. These presumably have arisen by recombination between the helper and 'transforming' sequences derived from the cells. Moloney sarcoma virus-transformed cells produce a new peptide, called sarcoma growth factor (SGF), that makes normal cells take on some of the properties of transformed cells. Studies with temperature-sensitive viral mutants show that the production of SGF is under the control of the transforming genes of the sarcoma virus.

Animals↗
PubMed1980

Biochemical characterization of endogenous type C virus information in differentiated and undifferentiated murine teratocarcinoma-derived cell lines.

Undifferentiated teratocarcinoma cells express sixfold-higher levels of endogenous xenotropic type C virus-related RNA than differentiated cells. Three species of polyadenylated viral RNA (35S, 24S, and 14S) have been identified in the undifferentiated teratocarcinoma cells. Paradoxically, neither viral particles nor viral proteins have been detected in these cells.

Animals↗
PubMed1980

Detection of novel murine mammary tumor viruses by interspecies immunoassays.

Radioimmunoassays were developed that can detect antigenic determinants common to mammary tumor viruses (MTV's) of four distinct Mus species: M. musculus, M. cervicolor, M. cookll, and M. caroll. The radioimmunoassays were based on the immunologic cross-reactivity observed between the murine mammary tumor viruses (MuMTV) of M. musculus and type B retrovirus isolated from M. cervicolor. Both of the glycoproteins of MuMTV (gp52, gp36) shared antigenic determinants with virions of M. cervicolor mammary tumor virus. Interspecies radioimmunoassays for gp52 and gp36 were developed and used to detect viruses in the milk of noninbred feral Mus species and MuMTV-related translational products in mammary tumors in these species. Type C and type D retroviruses, as well as the M432 retrovirus of M. cervicolor, did not react in either assay. Both interspecies immunoassays were therefore specific for the detection of distinct MuMTV-related antigenic determinants.

Animals↗
PubMed1979

Isolation of an endogenous type C virus related to the infectious primate type C viruses from the Asian rodent Vandeleuria oleracea.

A tissue culture line derived from the Asian rodent Vandeleuria oleracea has been shown to release an infectious, xenotropic type C virus. The virus-associated reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) and the major internal protein p30 are immunologically related to the respective proteins of the woolly monkey-gibbon ape group of infectious primate viruses. By these criteria the V. oleracea viral isolate is similar to the murine type C-I class of endogenous retroviruses and has been designated Vand C-I. Nucleic acid homology studies show that V. oleracea cellular DNA shares similar levels of homology with DNA from members of the Mus and Rattus genera and lower levels of homology with other rodent genera. The Vand C-I viral genome is present in V. oleracea cellular DNA in multiple copies, and partially related sequences can be detected in other rodent genera. These results support the conclusion that the Vand C-I viral genome is genetically transmitted in V. oleracea and that the type C-I class of endogenous retroviral genes has been highly conserved during evolution.

Animals↗
PubMed1978

A mutation to 5-methyltryptophan dependence in the tryptophan (trp) operon of Salmonella typhimurium. II. Studies of 5-methyltryptophan-dependent mutants and their revertants.

Mutants of S. typhimurium with a defect in the first structural gene of the trp operon can utilize anthranilic acid (AA) as a growth factor. Among a group of 5-methyltryptophan (MT) resistant derivatives of trpA mutants we encountered several with a novel phenotype: they actually grew better in the presence of MT than in its absence. Normally MT inhibits growth of S. typhimurium at the concentration we employed due to its ability to act as co-repressor of the trp operon and as a feedback inhibitor of anthranilate synthetase (AS) the first enzyme for tryptophan biosynthesis. Mutations to MT-dependence were only found in strains carrying extremely polar trpA mutations. In all cases analyzed, mutations causing MT-dependence mapped at the extreme operator distal end of trpA. The mutation trpA515 responsible for MT-dependence in strain SO61 (genotype trpA49trpA515) was recombined away from the polar mutation. The strain thus obtained, SO495 was totally dependent on MT for growth on AA supplement. Strain SO495 lacks AS and under repressing growth conditions synthesizes the trp enzymes constitutively at 2--3 times the basal level. Under derepression, while the levels of the distal enzymes, as represented by tryptophan synthetase--beta subunit (TSbeta), did not increase there was a marked drop in the activity of anthranilate-PRPP phosphoribosyltransferase, (PRT) the enzyme catalyzing the second step of tryptophan biosynthesis. trpA515 was found to revert to prototrophy at a low frequency (about 10(-8)) which was not increased by chemical mutagens or ultraviolet radiation. In contrast, it was found to revert to MT-independence (growth on AA in the absence of MT) at a fairly high spontaneous frequency (about 10(-6)) and this frequency could be increased approximately tenfold by mutagens causing base substitutions or deletions but not by frameshift mutagens. About one hundred MT-independent revertants of trpA515 were mapped and found to fall into three general classes: (A) mutations at or near the trpA515 site (B) secondary mutations located upstream from trpA515, (C) deletions of various sizes. Based on a detailed genetic and physiological study of twelve representative MT-independent revertants, it appears that trpA515 may be caused by the insertion of a piece of DNA with some of the properties described for the IS elements found in Escherichia coli. The trpA515 insertion should contain (in this order), a transcription terminator, a low efficiency promoter and, probably, a translation start signal.

Chromosome Mapping↗
PubMed1978

Characterization of a new virus from Mus cervicolor immunologically related to the mouse mammary tumor virus.

A virus, similar to the murine mammary tumor viruses (MuMTV) of the laboratory mouse Mus musculus, was identified in the milk of M. cervicolor popaeus mice. The virus was morphologically indistinguishable from the type-B MuMTV and was thus termed MC-MTV. Radioimmunoassays for the 52,000-dalton major envelope glycoprotein and the 28,000-dalton major internal protein of MuMTV demonstrated that MC-MTV shared some antigenic determinants with both of these MuMTV proteins. This reactivity was clearly different, however, from that observed with all MuMTV tested from M. musculus. MC-MTV had a density of 1.16 g/ml in sucrose and a virion-associated DNA polymerase with a divalent cation preference for Mg2+ over Mn2+. Radioimmunoassays clearly differentiated MC-MTV from the other viruses previously identified from M. cervicolor, i.e., M432, CERV-CI, and CERV-CII. These studies thus identified the first virus from another species that is immunologically related to the MuMTV of M. musculus. Particles similar to MC-MTV were also observed in a spontaneous M. cervicolor popaeus mammary tumor.

Animals↗
PubMed1977

Two distinct endogenous type C viruses isolated from the asian rodent Mus cervicolor: conservation of virogene sequences in related rodent species.

The cocultivation of a lung cell line from the Southeast Asian mouse Mus cervicolor with cells from heterologous species has resulted in the isolation of two new distinct type C viruses. Both viruses are endogenous to M. cervicolor and are present in multiple copies in the cellular DNA of these mice. One of the viruses, designated M. cervicolor type CI, replicates readily in the SIRC rabbit cell line and is antigenically related to the infectious primate type C viruses isolated from a woolly monkey (simian sarcoma-associated virus) and gibbon apes (gibbon ape leukemia virus). This virus is also closely related by both immunological and nucleic acid hybridization criteria to a type C virus previously isolated from a second Asian murine species, Mus caroli. The isolation of the M. cervicolor type C I virus thus provides further evidence that the infectious primate type C viruses originated by trans-species infection of primates by an endogenous virus of mice. The second virus, designated M. cervicolor type C II, replicates well in various cell lines derived from the laboratory mouse Mus musculus. While antigenically related to type C viruses derived from M. musculus, the M. cervicolor type C II virus isolate can be readily distinguished from standard murine leukemia viruses. Both new type C viruses from M. cervicolor are unrelated to the previously described retrovirus (M432) isolated from the same Mus species. The DNA of M. cervicolor therefore contains multiple copies of at least three distinct classes of endogenous viral genes. An examination of the cellular DNA of other rodent species for nucleic acid sequences related to the genomes of both M. cervicolor type C I and II reveals that both viruses have been highly conserved evolutionarily, and that other species of rodents, such as laboratory mice and rats, contain endogenous virogenes related to those in the DNA of M. cervicolor.

Animals↗
PubMed1976

Bovine leukemia virus genes in the DNA of leukemic cattle.

Reverse transcripts of the rna genome of the bovine leukemia virus (BLV) as well as 125I-labeled BLV RNA hybridize to the DNA of tissues from leukemic cattle with the adult form of the disease but not to bovine thymic lymphoma or normal bovine tissues.

Animals↗