Feline sarcoma virus

Each cell of the human body carries the potential to become cancerous in the form of its proto-oncogenes. The case of the src gene is far from unique. A great many proto-oncogenes have been discovered some of the best known are myc, myb, ras, fes, fins, fos, and jun (these names derive from the retrovirus in which they were discovered e.g., ras comes from a rat sarcoma virus and fes from a feline sarcoma virus). It follows that each of our cells harbors a number of protooncogenes, each of which may become activated and contribute to the formation of a tumor. 

The results from a study employing a human cell line showed that neither 5 nor 50 ppm petroleum-derived JP-5 (PD-JP5) interfered with Snyder-Theilen feline sarcoma virus (ST-FeSV)-directed transformation of human foreskin fibroblastic cells (Blakeslee et al. 1983). Higher concentrations ( 100 ppm) were cytotoxic. It was reported that marine diesel fuel failed to inhibit transformation in this assay, but data were not shown. The study authors consider this in vitro assay to be a useful predictor of carcinogenesis since several known carcinogens have been shown to suppress transformation in cells infected with the ST-FeSV virus by blocking a specific virus gene function (i.e., transformation) noncarcinogens do not inhibit virus-induced cell transformation in this test system. 

Todaro, G. J., De Larco, J. E., and Cohen, S. (1976). Transformation by murine and feline sarcoma viruses specifically blocks binding of epidermal growth factor to cells. Nature 264, 26-31. 

FGR is a member of the Src family nonreceptor tyrosine kinases. The oncogenic FGR is a product of the v-fgr gene of the feline sarcoma virus Gardner-Rasheed. 

Stem cell factor, SCF, also called steel factor or mast cell growth factor is a cytokine that stimulates the proliferation of myeloid and lymphoid hemopoietic progenitor cells. SCF is a ligand of the receptor tyrosine kinase, c-KIT, a protoonct ene. The KIT oncogene is the gene of a transforming feline sarcoma virus. 

Feline sarcoma virus (strain Gardner-Arnstein [60]) [60] <26> Feline sarcoma virus (strain Snyder-Theilen [60]) [60]... 

Feline sarcoma virus (strain Gardner-Rasheed [61]) [61] <28> Feline sarcoma virus (strain McDonough [62]) [62, 63] <29> Caenorhabditis elegans [64]... 

Feline sarcoma virus (strain Hardy-Zuckerman 4 [65]) [65] <31> Homo sapiens [66, 67, 68, 69]... 

Colony-stimulating factor (CSF-1) receptor c-fms gpl40-> v-jms McDonough feline sarcoma virus... 

Sarcoma viruses. This group includes avian sarcoma virus (ASV), Rous-associated virus and other fowl sarcoma viruses murine sarcoma virus (MSV) (28, 265, 454) feline sarcoma virus (FeSV) (298) and sarcoma viruses of primates, including woolly monkey (SSV) (516) and gibbon ape (GaSV). 

Abbreviations Ad, Adenovirus EBV, Epstein-Barr virus FeLV, Feline leukemia virus FeSV, Feline sarcoma virus GaLV, Gibbon ape lymphosarcoma virus HVA, Herpesvirus ateles HVS, Herpesvirus saimiri MV, Monkey virus PML, Progressive multifocal leukoencephalopathy associated with three SV40-like viruses SSV-1, Woolly monkey fibrosarcoma virus SV, Simian virus. [Adapted from (477)]. 

PMEA and its congeners are more effective in vivo than could be predicted from their in vitro potency. While less potent as an antiretrovirus agent than AZT in vitro, PMEA proved clearly superior to AZT when the two drugs were compared for their effectiveness in vivo, in mice infected with murine Moloney sarcoma virus [51,52]. PMEA was also shown to be effective against various other retrovirus infections, including Friend leukemia virus (FLV), Rauscher leukemia virus (RLV), and LP-BM5 (murine AIDS) virus infection in mice, feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) infection in cats, and SIV infection in macaque (rhesus) monkeys (for review, see Ref. 53). In the latter model [54], again PMEA proved far superior to AZT in suppressing several parameters of the disease. 

Retroviruses encode a protease (PR) responsible for cleaving polyprotein precursors, and such processing is essential for proper virion assembly and maturation. Based on the presence of a sequence Asp-Ser/Thr-Gly in the active sites of retroviral proteases (1) and their inhibition in vitro by pepstatin (2-7), these enzymes have been classified as members of the aspartic protease family. Crystal structures have been determined for the proteases from Rous sarcoma virus (RSV PR) (8), from two variants and several mutants of the human immunodeficiency vims (HIV PR) (9-11), from feline immunodeficiency virus (FIV PR) (12) and from equine infectious anemia vims (EIAV PR) (13). Aspartic proteases contain a single active site which includes two aspartates. In apoenzymes, the two catalytic Asp residues from the active site triad have been found to be in hydrogen bond contact with a water molecule (10). Mutations of the active site Asp25 in HIV-1 PR into Asn (14,15), Thr (3) or Ala (4,16,17) led to an inactive enzyme. Similarly, the RSV PR was inactivated by mutation of its active site Asp to He (18). 

Sarma, P.S., A. Sharar, V. Walters, and M. Gardner. 1974. A survey of cats and humans for prevalence of feline leukemia-sarcoma virus neutralizing serum antibodies. Proc. Soc. Exp. Biol. Med. 145 560-564. 

Spumavirus (the foamy viruses) Lentivirus (human, feline, simian, and bovine immunodeficiency viruses). Enveloped, spherical, negative-sense, and ssRNA (two identical strands). Synthesis occurs in the host cell cytoplasm maturation involves budding through the host cell plasma membrane. These viruses contain the enzyme reverse transcriptase. The retroviruses (except the Spumavirus and Lentivirus genera) represent the RNA tiunor viruses, causing leukemias, carcinomas, and sarcomas. 

---