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J Virol, July 1998, p. 5517-5525, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Min Gong,1 Helen L. Semus,1 Kelly J. Bird,1 Brian J. Stramer,1 and Alanna Ruddell2,*

Department of Microbiology and Immunology and Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642,1 and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 981092

Received 13 January 1998/Accepted 26 March 1998

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.


* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, MS C2-023, 1100 Fairview Ave. N., P.O. Box 19024, Seattle, WA 98109-1024. Phone: (206) 667-5496. Fax: (206) 667-6523. E-mail: aruddell{at}fred.fhcrc.org.


J Virol, July 1998, p. 5517-5525, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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Copyright © 1998 by the American Society for Microbiology. All rights reserved.