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Journal of Virology, October 2000, p. 9090-9098, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Adeno-Associated Virus Type 2 Rep Protein Inhibits Human Papillomavirus Type 16 E2 Recruitment of the Transcriptional Coactivator p300

Alessandro Marcello,1 Paola Massimi,2 Lawrence Banks,2 and Mauro Giacca1,3,*

Molecular Medicine1 and Virology2 Laboratories, International Center for Genetic Engineering and Biotechnology, 34012 Trieste, and Scuola Normale Superiore, 56126 Pisa,3 Italy

Received 24 April 2000/Accepted 5 July 2000

Infection by human adeno-associated virus type 2 (AAV2) is a possible protective factor in the development of cervical carcinomas associated with human papillomaviruses (HPV). The replicative proteins of AAV2 (Rep) have been implicated in the inhibition of papillomavirus replication and transforming activities, although the molecular events underlying these effects are poorly understood. We observed that each of the four forms of AAV2 Rep inhibited the E1- and E2-driven replication of oncogenic HPV type 16 (HPV16). Rep40, corresponding to the C-terminal domain of all Rep proteins, inhibited both HPV DNA replication and HPV16 E2-mediated transactivation. Rep40 specifically bound the N-terminal transactivation domain of HPV16 E2 both in vitro and in vivo. This interaction was found to specifically disrupt the binding of E2 to the cellular transcriptional coactivator p300. Accordingly, the inhibitory effect of Rep on HPV16 E2 transactivation was rescued by the overexpression of p300. These data indicate a novel role of Rep in the down-regulation of papillomaviruses through inhibition of complex formation between the HPV16 E2 transcriptional activator and its cellular coactivator, p300.

* Corresponding author. Mailing address: Molecular Medicine Laboratory, ICGEB, Padriciano 99, 34012 Trieste, Italy. Phone: 39-040-3757.324. Fax: 39-040-226555. E-mail: giacca{at}icgeb.trieste.it.

Journal of Virology, October 2000, p. 9090-9098, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

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