Identification of nucleotide sequences which may encode the oncogenic capacity of avian retrovirus MC29

Abstract

The retrovirus strain MC29 induces a variety of tumors in chickens, including myelocytomatosis and carcinomas of the kidney and liver. In addition, the virus can transform cultures of embryonic avian macrophages and fibroblasts. We have characterized the genome of MC29 virus and have identified nucleotide sequences that may encode the oncogenic potential of the virus. MC29 virus can replicate only with the assistance of a related helper virus. The defect in replication is apparently a consequence of a deletion in one or more viral genes: the haploid genome of the MC29 virus has a molecular weight of ca. 1.7 x 106, whereas the genome of the helper virus MCAV has a molecular weight of ca. 3.1 x 106. Although MC29 virus transforms fibroblasts in culture, its genome has no detectable homology with the gene src that is responsible for transformation of fibroblasts by avian sarcoma viruses. We prepared radioactive single-stranded DNA complementary to nucleotide sequences present in the genome of MC29 virus but not in the genome of MCAV (cDNAMc29). If they are contiguous, these sequences (ca. 1,500 nucleotides) are sufficiently complex to encode at least one protein. Homologous sequences were not detectable in several strains of avian sarcoma viruses or in an endogenous virus of chickens. Our findings confirm and extend recent reports from other laboratories and lead to the conclusion that MC29 virus may contain a previously unidentified gene(s) that is capable of transforming several distinct target cells. The evolutionary origins of this putative gene and its location on the viral genome can be explored with cDNAMC29.

Two different types of transcription for the myelocytomatosis viruses MH2 and CMII.

“…Total polyadenylated cellular RNAs from non-producer quail cells transformed by MH2 (clone MH2 QB2) or CMII (clone CMII QAI, Graf et al, 1977), as well as MC29 (clone MC29 Q8, Bister et al, 1977) for comparison, was analyzed by gel electrophoresis and blotting onto diazobenzyloxymethyl (DBM) paper. The blots were hybridized using nick-translated 32P-labelled probes (Rigby et al, 1977) from the genes gag, pol and env (3' or 5' region), prepared as described (Saule et al, 1982) ( Figure 1), or utilizing: cDNAS' (Friedrich et al, 1977) cDNAmyc (Sheiness et al, 1978) and cDNArep (representative of ALV RNA, Saule et al, 1982).…”

“…The preparation and characterization of all probes was extensively described in Saule et al (1982). The cDNAmyc synthesized in the exogenous reaction (Taylor et al, 1976), using 50-70S RNA viral templates (MC29 RAV2) and purified avian myeloblastosis virus polymerase, was selected as described by Sheiness et al (1978). Representative cDNA (cDNArep) from RAV2 was prepared according to Saule et al (1982).…”

Differential modulation of plasminogen activator gene expression by oncogene-encoded protein tyrosine kinases.

“…Virus stocks of the SH2 domain deletion mutants d1145 and d1165 were provided by J. T. Parsons (University of Virginia) (83). CEF infected with Y73 (containing v-yes), MC29 (containing v-myc), and SRAv-ski (containing v-ski) were provided by E. Stavnezer (University of Cincinnati) (14, 38,42,69,72). An avian sarcoma virus 17 (ASV-17) (containing v-jun) virus stock was provided by P. Vogt (University of Southern California) (53).…”

Transformation of Immature Lymphoid Cells by Abelson Murine Leukemia Virus

“…The low copy number of the relevant mouse gene suggests that it is probably not a gene contained in a virusrelated sequence because all such genes occur in multiple copies in animal genomes (Baltimore 1974). A number of other transforming retroviruses appear to have arisen in a manner similar to A-MuLV including the murine sarcoma virus, the Rous sarcoma virus, the feline sarcoma virus, and a number of avian leukosis viruses (Scolnick et al 1973, Frankel & Fischinger 1977, Stehelin et al 1976b, Sheiness et al 1978, Frankel et al 1979. In fact, it almost appears a general rule that viruses able to directly transform cells in culture have a hybrid structure in which a central portion of the genome is derived from normal cellular information.…”