FUNCTIONAL INTERACTION BETWEEN THE HCMV IE2 TRANSACTIVATOR AND THE RETINOBLASTOMA PROTEIN

The 86 kDa immediate early IE2 protein of human cytomegalovirus (HCMV) can activate transcription of both viral and cellular genes and can r epress transcription from its own promoter. Using two in vivo assays, we provide evidence of a functional interaction between IE2 and the re tinoblastoma (RB) protein: IE2 alleviates RB-induced repression of a p romoter bearing E2F binding sites and RB alleviates IE2-mediated repre ssion of its own promoter. These functional effects are likely to be a result of a direct contact between IE2 and RB, which we can demonstra te both in vitro and in HCMV-infected cells. The interaction between I E2 and RB shows similar characteristics to the interaction between RB and E1A. First, binding to IE2 requires an intact RB pocket domain. Se condly, the binding is sensitive to the phosphorylation state of RB, b ecause cyclin A-CDK-induced phosphorylation of RB diminishes IE2 bindi ng. Thirdly, the IE2 domain required for RB binding is separate to the domains necessary for TBP and TFIIB binding. Our results demonstrate that large and small DNA viruses have a common interface with the host cell, namely the association, with the RB tumour suppressor protein.