5' long terminal repeats of myc-associated proviruses appear structurally intact but are functionally impaired in tumors induced by avian leukosis viruses.
B-cell lymphomas induced in chickens infected with avian leukosis viruses are characterized by integration of the virus within the cellular myc locus and alteration of c-myc expression. Although avian leukosis viruses are intact, replication-competent retroviruses, the structures of many myc-associated proviruses are altered by deletions, raising the possibility that proviral defectiveness plays an essential role in oncogenesis. We found that all myc-associated proviruses in 21 independent tumors had deletions, which were confined to the viral genome and did not extend into adjacent cellular sequences. Deletions were not random but, in at least 85% of the myc-associated proviruses, involved a region near the 5' end of the proviral genome where elements implicated in control of viral gene expression have been localized. A second class of deletions involved sequences in the 3' half of the viral genome and included the splice acceptor site used in generating viral env mRNA. Both the 5' and 3' long terminal repeats of myc-associated proviruses appeared to be structurally intact in most tumors, although the 5' long terminal repeats were not involved in expression of either U5-myc transcripts or detectable steady-state viral RNAs. A complex array of repeated sequence elements surrounded the junctions of the internal deletions in two myc-associated proviruses. The organization of the deleted proviruses was similar to that of deleted unintegrated viral molecules, consistent with a model in which deletions occurred prior to integration.
D001354:Avian Leukosis Virus / Q000235:genetics*; D001483:Base Sequence; D002872:Chromosome Deletion; D004273:DNA, Neoplasm / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D005786:Gene Expression Regulation; D005814:Genes, Viral; D009374:Neoplasms, Experimental / Q000235:genetics*; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid
D004273:DNA, Neoplasm; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral