Histone acetyltransferases (HATs) play a key role in transcription control, cell proliferation and differentiation by modulating chromatin structure; however, little is known about their own regulation. Here we show that expression of the viral oncoprotein SV40 T antigen increases histone acetylation and global cellular HAT activities. In addition, it enhances CREB-binding protein HAT activity and modulates its transcriptional activity. Finally, we show that inhibition of cellular histone deacetylases by trichostatin A increases the SV40 infectivity rate. These findings highlight the importance of histone acetylation in the regulation of the cell cycle by oncoviral proteins.