Fujinami sarcoma virus: An avian RNA tumor virus with a unique transforming gene

Abstract

The oncogenic properties and RNA of the Fujinami avian sarcoma virus (FSV) and the protein it encodes were investigated and compared to those of other avian tumor viruses with sarcomagenic properties such as Rous sarcoma virus and the acute leukemia viruses MC29 and erythroblastosis virus. Cloned stocks of FSV caused sarcomas in all chickens inoculated and were found to contain a 4.5-kilobase (kb) and an 8.5-kb RNA species. The 4.5-kb RNA was identified as the genome of defective FSV because it was absent from nondefective FSV-associated helper virus and because the titer of focusforming units increased with the ratio of 4.5-kb to 8.5-kb RNA in virus preparations. This is, then, the smallest known tumor virus RNA with a transforming function. Comparisons with other viral RNAs, based on oligonucleotide mapping and molecular hybridization, indicated that 4.5-kb FSV RNA contains a 5' gag gene-related sequence of 1 kb, an internal specific sequence of about 3 kb that is unrelated to Rous sarcoma virus, MC29, and erythroblastosis virus, and a 3'-terminal sequence of about 0.5 kb related to the conserved C region of avian tumor viruses. The lack of some or all nucleotide sequences of the essential virion genes, gag, pol, and env, and the isolation of FSV-transformed nonproducer cell clones indicated that FSV is replication defective. A 140,000-dalton, gag-related nonstructural protein was found in FSV-transformed producer and nonproducer cells and was translated in vitro from full-length FSV RNA. This protein is expected to have a transforming function both because its intracellular concentration showed a positive correlation with the percentage of transformed cells in a culture and because FSV is unlikely to code for major additional proteins since the genetic complexities of FSV RNA and the FSV protein are almost the same. It is concluded that the transforming onc gene of FSV is distinct from that of Rous sarcoma virus and other avian tumor viruses with sarcomagenic properties. Hence, multiple mechanisms exist for sarcomagenic transformation of avian cells.There are a number of sarcomagenic viruses in the avian tumor virus group that fall into discrete RNA subgroups, defined here on the basis of helper-virus unrelated, specific RNA sequences.[See below and ref. 1. Both defective and nondefective viruses can be classified consistently by using RNA subgroups (1). In contrast, only nondefective viruses can be classified on the basis of envelope subgroups (2). ] The Rous subgroup includes the replication-defective Bryan Rous sarcoma virus (RSV), the nondefective Schmidt-Ruppin strain, and the Prague strain of RSV (2, 3). The most common neoplasm produced by the RSV RNA subgroup of viruses is a sarcoma. The Rous subgroup is defined by a related class of transforming genes of 1.5 kilobases (kb) termed src (1, 4-7), which are located near the 3' end of viral RNA (6) and encode a 60-kilodalton nonstructural protein product thought to have a transforming function (8, 9). The ES4 strain of avian erythroblastosis virus...

Preferential expression of the c-fps protein in chicken macrophages and granulocytic cells.

“…2,700 nucleotides called v-fps (10,13,19). This virus encodes a transforming protein of 1,182 amino acids, P130, which exhibits tyrosine kinase activity and is phosphorylated in vivo (6, 9).…”

OK10, an avian acute leukemia virus of the MC29 subgroup with a unique genetic structure

“…The (1,2,(9)(10)(11)(12)(13)(14)(15)(16)(17). In contrast to any of these defective transforming viruses, the gag-related, nonstructural protein of OK10 also contains pol gene determinants (8).…”

Antipeptide antiserum identifies a widely distributed cellular tyrosine kinase related to but distinct from the c-fps/fes-encoded protein.

“…Accordingly, we prepared an antiserum directed against a synthetic peptide corresponding to a very conserved region in the transforming protein of Fujinami sarcoma virus (FSV), an acutely transforming avian sarcoma virus whose transforming gene is v-fps (20,28). This antiserum specifically recognized the transforming protein of FSV (P140), it cross-reacted with the gene products of avian and mammalian fps/fes, and in addition, it recognized a new cellular protein of 94,000 daltons (NCP94) in avian and mammalian cells (13).…”