Adenovirus inhibition of cellular protein synthesis and the specific translation of late viral mRNAs

Abstract

The late phase of adenovirus (Ad) infection is marked by the inhibition of cellular protein synthesis, the preferential translation of late viral mRNAs and resistance to the translation inhibitory effects of interferon. This article reviews the evidence for each form of translational control by the virus, and the molecular mechanisms that are likely involved. Insensitivity to interferon is clearly provided by a small viral transcript known as VAI RNA, which prevents the activation and antiviral activities of the interferon induced kinase, DAI. Suppression of cellular protein synthesis and preferential translation of late viral mRNAs involves several translational control mechanisms mediated by Ad: (1) inactivation of initiation factor eIF-4F through the dephosphorylation of its cap binding protein component; (2) the unusual ability of late viral mRNAs to translate with little if any requirement for eIF-4F; and (3) additional but poorly understood activities of the late viral 100k protein, activated DAI kinase and VAI RNA.