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Journal of Virology, September 2002, p. 9526-9532, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9526-9532.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Induction and Bypass of p53 during Productive Infection by Polyomavirus

Dilip Dey,,{dagger} Jean Dahl, Sayeon Cho,,{ddagger} and Thomas L. Benjamin*

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

Received 1 March 2002/ Accepted 19 June 2002

Lytic infection by polyomavirus leads to elevated levels of p53 and induction of p53 target genes p21Cip1/WAF1 (p21) and BAX. This is seen both in polyomavirus-infected primary mouse cell cultures and in kidney tissue of infected mice. Stabilization of p53 and induction of a p53 response are accompanied by phosphorylation of p53 on serine 18, mimicking a DNA damage response. Stabilization of p53 does not depend on p19Arf interaction with mdm2. Cells infected by a mutant virus defective in binding pRb and in inducing G1-to-S progression show a greatly diminished p53 response. However, cells infected by wild-type virus and blocked from entering S phase by addition of mimosine still show a p53 response. These results suggest a role of E2F target genes in inducing a p53 response. Polyomavirus large T antigen coprecipitates with p53 phosphorylated on serine 18 and also with p21Cip1/WAF1. Implications of these and other findings on possible mechanisms of induction and override of p53 functions during productive infection by polyomavirus are discussed.

* Corresponding author. Mailing address: Department of Pathology, Harvard Medical School, 200 Longwood Ave. D2-230, Boston, MA 02115. Phone: (617) 432-1960. Fax: (617) 277-5291. E-mail: thomas_benjamin{at}hms.harvard.edu.

{dagger} Present address: Division of Biology, University of California at San Diego, La Jolla, CA 92093-0366.

{ddagger} Present address: Proteome Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Taejon 305-33, Korea.

Journal of Virology, September 2002, p. 9526-9532, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9526-9532.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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