Adeno-associated virus type 2 Rep protein inhibits human papillomavirus type 16 E2 recruitment of the transcriptional coactivator p300

Infection by human adeno-associated virus type 2 (AAV2) is a possible prote ctive factor in the development of cervical carcinomas associated with huma n papillomaviruses (BPV). 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 poo rly understood, me observed that each of the four forms of AAV2 Rep inhibit ed the E1- and E2-driven replication of oncogenic HPV type 16 (HPV16), Rep4 0, corresponding to the C-terminal domain of all Rep proteins, inhibited bo th HPV DNA. replication and HPV16 E2-mediated transactivation. Rep40 specif ically bound the N-terminal transactivation domain of HPV16 E2 both in vitr o and in vivo. This interaction was found to specifically disrupt the bindi ng of E2 to the cellular transcriptional coactivator p300. Accordingly, the inhibitory effect of Rep on HPV16 E2 transactivation was rescued by the ov erexpression of p300. These data indicate a novel role of Rep in the down-r egulation of papillomaviruses through inhibition of complex formation betwe en the HPV16 E2 transcriptional activator and its cellular coactivator, p30 0.