MODIFICATION OF EUKARYOTIC INITIATION-FACTOR 4F DURING INFECTION BY INFLUENZA-VIRUS

Influenza virus infection of cells is accompanied by a striking shutof f of cellular protein synthesis, resulting in the exclusive translatio n of viral mRNAs. The mechanism for control of cellular protein synthe sis by influenza virus is poorly understood, but several translation p roperties of influenza virus mRNAs which are potentially involved have been described. Influenza virus mRNAs possess the surprising ability to translate in the presence of inhibitory levels of inactive (phospho rylated) eukaryotic initiation factor 2 (eIF-2). In addition, influenz a virus mRNAs were shown to be capable of translating in cells during the late phase of adenovirus infection but not in cells infected by po liovirus. Since both adenovirus and poliovirus facilitate virus-specif ic translation by impairing the activity of initiation factor eIF-4F ( cap-binding protein complex) but through different mechanisms, we inve stigated the translation properties of influenza virus mRNAs in more d etail. We show that influenza virus infection is associated with the s ignificant dephosphorylation and inactivation of eIF-4E (cap-binding p rotein), a component of eIF-4F, and accordingly that influenza virus m RNAs possess a moderate ability to translate by using low levels of eI F-4F. We also confirm the ability of influenza virus mRNAs to translat e in the presence of high levels of inactive (phosphorylated) eIF-2 bu t to a more limited extent than reported previously. We suggest a pote ntial mechanism for the regulation of protein synthesis by influenza v irus involving a decreased requirement for large pools of active eIF-4 F and eIF-2.