Analysis of avian leukosis virus DNA and RNA in bursal tumors: Viral gene expression is not required for maintenance of the tumor state

Gregory S. Payne, Sara A. Courtneidge, Lyman B. Crittenden, Aly M. Fadly, J. Michael Bishop, Harold E. Varmus

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

Each of twelve tumors induced by either Rous-associated virus-1 or -2 (RAV-1 or RAV-2) contained a predominant population of cells with ALV proviruses integrated at common sites, consistent with a clonal origin. Seven of nine RAV-2-induced bursal tumors contained single proviruses, and all seven solitary proviruses had suffered deletions. The detailed structures of four of these proviruses show that major deletions had occurred near or at the 5′ ends, spanning sequences potentially important in the production of viral RNA. One provirus also lacked most of the information coding for the replicative functions of the virus. Restriction maps suggest that these four proviruses were inserted in similar regions of the host genome. We have studied virus-specific RNA in four bursal tumors and four cell lines derived from bursal tumors. No normal viral RNA species were detectable in three tumors containing single aberrant proviruses. However, transcripts of 2.2 kb which reacted only with a hybridization probe specific for the 5′ end of viral RNA were observed in one of these three tumors. Analogous species, varying in length from 1.5 to 6.0 kb, were observed in a fourth bursal tumor with multiple proviruses and in all four cell lines. (This tumor and the cell lines also contained normal species of ALV mRNA and apparently normal proviral DNA.) The structures of the aberrant proviruses and the absence of normal viral RNA in some tumors indicate that expression of viral genes is not required for maintenance of the tumor phenotype. In at least some cases, the mechanism of oncogenesis may involve stimulation of transcription of flanking cellular sequences by a viral promoter.

Original languageEnglish (US)
Pages (from-to)311-322
Number of pages12
JournalCell
Volume23
Issue number2
DOIs
StatePublished - Feb 1981

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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