TRANSLATIONAL CONTROL BY INFLUENZA-VIRUS - SELECTIVE TRANSLATION IS MEDIATED BY SEQUENCES WITHIN THE VIRAL MESSENGER-RNA 5'-UNTRANSLATED REGION

In cells infected by influenza virus type A, host cell protein synthes is declines rapidly and dramatically, while influenza viral protein sy nthesis occurs efficiently throughout infection. Previously, we had sh own that the selective translation of influenza viral mRNAs in infecte d cells occurred in a cap-dependent manner and was due at least in par t to structures inherent in the mRNAs. Using chimeras containing the n oncoding and coding regions of cellular and viral mRNAs, we can now re port that the selective translation is mediated by sequences within th e 5'-untranslated regions (UTR) of the viral mRNAs. Polysome analysis confirmed that a 45-nucleotide sequence contained in the 5'-UTR of the influenza viral nucleocapsid protein was necessary and sufficient to allow the host cell translational machinery to discriminate between vi ral and cellular mRNAs. In reciprocal experiments in which the 5'-UTR of the cellular mRNA-secreted embryonic alkaline phosphatase replaced the nucleocapsid protein 5'-UTR, viral protein synthesis was inhibited in virus-infected cells, resembling host protein synthesis. Finally, we demonstrated that the 5'-UTR of another influenza viral mRNA, that encoding the nonstructural protein, also conferred resistance to the s hutoff of protein synthesis in influenza virus-infected cells.