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J Virol, July 1998, p. 5517-5525, Vol. 72, No. 7
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.
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
*
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.
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