Differential Selection of Cells with Proviral c- myc and c- erbB Integrations after Avian Leukosis Virus Infection

Abstract

Avian leukosis virus (ALV) infection induces bursal lymphomas in chickens after proviral integration within the c- myc proto-oncogene and induces erythroblastosis after integration within the c- erbB proto-oncogene. A nested PCR assay was used to analyze the appearance of these integrations at an early stage of tumor induction after infection of embryos. Five to eight distinct proviral c- myc integration events were amplified from bursas of infected 35-day-old birds, in good agreement with the number of transformed bursal follicles arising with these integrations. Cells containing these integrations are remarkably common, with an estimated 1 in 350 bursal cells having proviral c- myc integrations. These integrations were clustered within the 3′ half of c- myc intron 1, in a pattern similar to that observed in bursal lymphomas. Bone marrow and spleen showed a similar number and pattern of integrations clustered within 3′ c- myc intron 1, indicating that this region is a common integration target whether or not that tissue undergoes tumor induction. While all tissues showed equivalent levels of viral infection, cells with c- myc integrations were much more abundant in the bursa than in other tissues, indicating that cells with proviral c- myc integrations are preferentially expanded within the bursal environment. Proviral integration within the c- erbB gene was also analyzed, to detect clustered c- erbB intron 14 integrations associated with erythroblastosis. Proviral c- erbB integrations were equally abundant in the bone marrow, spleen, and bursa. These integrations were randomly situated upstream of c- erbB exon 15, indicating that cells carrying 3′ intron 14 integrations must be selected during induction of erythroblastosis.