McDonough feline sarcoma virus: characterization of the molecularly cloned provirus and its feline oncogene (v-fms)

Abstract

The genetic structure of the McDonough strain of feline sarcoma virus (SM-FeSV) was deduced by analysis of molecularly cloned, transforming proviral DNA. The 8.2-kilobase pair SM-FeSV provirus is longer than those of other feline sarcoma viruses and contains a transforming gene (v-fms) flanked by sequences derived from feline leukemia virus. The order of genes with respect to viral RNA is 5'-gag-fms-env-3', in which the entire feline leukemia virus env gene and an almost complete gag sequence are represented. Transfection of NIH/3T3 cells with cloned SM-FeSV proviral DNA induced foci of morphologically transformed cells which expressed SM-FeSV gene products and contained rescuable sarcoma viral genomes. Cells transformed by viral infection or after transfection with cloned proviral DNA expressed the polyprotein (P1700ag-fms) characteristic of the SM-FeSV strain. Two proteolytic cleavage products (Pl2OfmS and pp55sag) were also found in immunoprecipitates from metabolically labeled, transformed cells. An additional polypeptide, detected at comparatively low levels in SM-FeSV transformants, was indistinguishable in size and antigenicity from the envelope precursor (gPr85env) of feline leukemia virus. The complexity of the v-fms gene (3.1 ± 0.3 kilobase pairs) is approximately twofold greater than the viral oncogene sequences (v-fes) of Snyder-Theilen and Gardner-Arnstein FeSV. By heteroduplex, restriction enzyme, and nucleic acid hybridization analyses, v-fms and v-fes sequences showed no detectable homology to one another. Radiolabeled DNA fragments representing portions of the two viral oncogenes hybridized to different EcoRl and HindIII fragments of normal cat cellular DNA. Cellular sequences related to v-fms (designated c-fms) were much more complex than c-fes and were distributed segmentally over more than 40 kilobase pairs in cat DNA. Comparative structural studies of the molecularly cloned proviruses of Snyder-Theilen, Gardner-Arnstein, and SM-FeSV showed that a region of the feline leukemia virus genome derived from the pol-env junction is represented adjacent to v-onc sequences in each FeSV strain and may have provided sequences preferred for recombination with cellular genes.

Discovery of the First Human Retro-Giant Virus: Description of its morphology, retroviral kinase and ability to induce tumours in mice

“…RT activity matched to the presence of retroviral antigens at EM immunogold. To test the presence of possible retroviral antigens expressed on the giant particles, we used anti-FeLV gag p27 moAb, used for its ability to bind conserved epitopes among different mammalian retroviruses [10][11][12][13][14][15][16] . At EM immunogold, both the large and satellite ~400 -450 nm giant viral particles shared the same retroviral nature, being specifically labelled by anti-FeLV gag p27 mo-Ab, (Figure 5).…”

Class III receptor tyrosine kinases: role in leukaemogenesis

“…The human fms proto‐oncogene (c‐fms, CD115), located on chromosome 5 at band 5q33.3, encodes a 972 amino acid transmembrane glycoprotein which functions as the receptor of the monocyte colony‐stimulating factor (M‐CSF or CSF‐1) (Sherr et al , 1985). The c‐fms gene is the cellular homologue of the v‐fms gene of the Susan McDonough strain of the feline sarcoma virus (Donner et al , 1982). In contrast to the human gene, the v‐fms gene product possesses constitutive kinase activity in the absence of ligand and will transform cells in vitro (Sacca et al , 1986; Morrison et al , 1988).…”

CSF‐1 control of C‐FMS expression in normal human bone marrow progenitors

“…C.J. Sherr and M. Roussel (Donner et al, 1982;Roussel et al, 1983). After digestion with ClaI and BamHI restriction enzymes, the 2.7 kb v-fms insert was purified by electroelution according to Sambrook et al (1989).…”