Acute leukemia viruses E26 and avian myeloblastosis virus have related transformation-specific RNA sequences but different genetic structures, gene products, and oncogenic properties

Abstract

Replication-defective acute leukemia viruses E26 and myeloblastosis virus (AMV) cause distinct leukemias although they belong to the same subgroup of oncogenic avian tumor viruses based on shared transformation-specific (onc) RNA sequences. E26 causes predominantly erythroblastosis in chicken and in quail; AMV induces a myeloid leukemia. Upon cultivation in vitro for > 1 mo., a majority of surviving hemopoietic cells of E26-infected animals bear myeloid markers similar to those of AMV-transformed cells. The genetic structure and gene products of E26 virus were analyzed for a comparison with those of AMV. An E26/helper virus complex was found to contain 2 RNA species: a 5.7-kilobase (kb) RNA that hybridizes with cloned AMV-specific proviral DNA and hence is probably the E26 genome; and an 8.5-kb RNA that is unrelated to AMV and represents helper virus RNA. Thus, E26 RNA is smaller than 7.5 kb AMV RNA. Hybridization of size-selected poly(A)-terminating E26 RNA fragments with AMV-specific DNA indicated that the shared specific sequences are located in the 5'' half of the E26 genome as opposed to a 3'' location in AMV RNA. In nonproducer cells transformed in vitro by E26, a gag-related nonstructural 135,000 daltonprotein (p135) was found. No gag (Pr76) or gag-pol (Pr180) precursors of essential virion proteins, which are present in AMV nonproducer cells, were obsreved, p135 was also found in cultured E26 virus producing cells of several leukemic chickens, and its intracellular concentration relative to that of the essential virion proteins encoded by the helper virus correlates with the ratio of E26 tohelper RNA in virions released by these cells. p135 is phosphorylated but not glycosylated; antigenically it is not relate dto the pol or env gene products. It appears to be coded for by a partial gag gene and by E26-specific RNA sequences, presumablyincluding those shared by AMV. Hence, AMV and E26 appear to use different strategies for the expression of related onc sequences: AMV is thought to encode a transforming protein via a subgenomic mRNA; E26 codes for a gag-related polyprotein via genomic RNA. Differences in the oncogenic properties of E26 and AMV apparently are due to differences in their genetic structures and gene products.