Modification of eukaryotic initiation factor 4F during infection by influenza virus.
Influenza virus infection of cells is accompanied by a striking shutoff of cellular protein synthesis, resulting in the exclusive translation of viral mRNAs. The mechanism for control of cellular protein synthesis by influenza virus is poorly understood, but several translation properties 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 (phosphorylated) eukaryotic initiation factor 2 (eIF-2). In addition, influenza virus mRNAs were shown to be capable of translating in cells during the late phase of adenovirus infection but not in cells infected by poliovirus. Since both adenovirus and poliovirus facilitate virus-specific translation by impairing the activity of initiation factor eIF-4F (cap-binding protein complex) but through different mechanisms, we investigated the translation properties of influenza virus mRNAs in more detail. We show that influenza virus infection is associated with the significant dephosphorylation and inactivation of eIF-4E (cap-binding protein), a component of eIF-4F, and accordingly that influenza virus mRNAs possess a moderate ability to translate by using low levels of eIF-4F. We also confirm the ability of influenza virus mRNAs to translate in the presence of high levels of inactive (phosphorylated) eIF-2 but to a more limited extent than reported previously. We suggest a potential mechanism for the regulation of protein synthesis by influenza virus involving a decreased requirement for large pools of active eIF-4F and eIF-2.
Feigenblum
D
D
Department of Biochemistry, University Medical Center, New York, New York 10016.
Schneider
R J
RJ
D002461:Cell Line, Transformed; D004789:Enzyme Activation; D005057:Eukaryotic Cells; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D039562:Eukaryotic Initiation Factor-4F; D006801:Humans; D009975:Orthomyxoviridae / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010750:Phosphoproteins / Q000096:biosynthesis; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D019892:eIF-2 Kinase
D015852:Eukaryotic Initiation Factor-2; D039562:Eukaryotic Initiation Factor-4F; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D011494:Protein Kinases; D019892:eIF-2 Kinase