Mechanism of c-erbB transduction: newly released transducing viruses retain poly(A) tracts of erbB transcripts and encode C-terminally intact erbB proteins.
We have previously shown that avian leukosis virus (ALV) induces erythroblastosis by insertional activation of the c-erbB gene. In 25% of the ALV-induced leukemic samples we have analyzed, acute retroviruses that have captured the activated erbB oncogene were released. The unusually high frequency at which erbB transduction occurs makes this an ideal system for studying the mechanism of oncogene transduction. In addition, these leukemic samples provide a rich source for the isolation of novel erbB-transducing viruses. We report here our characterization of several new erbB-transducing proviruses. The 5' recombination points of all these viruses mapped to the same intron in which proviral insertions cluster, supporting the hypothesis that transduction begins with proviral insertion near the oncogene. The 3' recombination points usually occurred within the 3' untranslated region downstream from the termination codon of the c-erbB gene. Three of the erbB-containing proviruses were molecularly cloned and analyzed in detail. Two of them were capable of releasing acute viruses, and interestingly, both retained poly(A) tracts of erbB messages in their genomes. A stretch of six adenosine residues in the ALV env gene appeared to mediate the 3' recombination events required for the generation of these viruses. These data provide further insight into the mechanism by which oncogenes are transduced into retroviral genomes.
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics* / Q000502:physiology; D001483:Base Sequence; D002645:Chickens; D005814:Genes, Viral; D007438:Introns; D004915:Leukemia, Erythroblastic, Acute / Q000209:etiology / Q000235:genetics; D007942:Leukemia, Experimental / Q000209:etiology / Q000235:genetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009857:Oncogenes; D011061:Poly A / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011533:Proviruses / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D014161:Transduction, Genetic
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D011061:Poly A