Abstract

In cells infected by influenza virus type A, host cell protein synthesis declines rapidly and dramatically, while influenza viral protein synthesis occurs efficiently throughout infection. Previously, we had shown that the selective translation of influenza viral mRNAs in infected cells occurred in a cap-dependent manner and was due at least in part to structures inherent in the mRNAs. Using chimeras containing the noncoding and coding regions of cellular and viral mRNAs, we can now report that the selective translation is mediated by sequences within the 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 viral 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 shutoff of protein synthesis in influenza virus-infected cells.

Highlights

  • Subjects otherwise stable and functional mRNAs already in the cytoplasm toblock at both the initiation and elongation stoefps translation (Katze et al, 1986). (iv) It encodes mRNAs with structural features that promote selective translation

  • In cells infected by influenza virus type A, host cell protein synthesis declines rapidlyanddramatically, while influenza viral proteisnynthesisoccurs efficiently throughout infection.Previously, we had shown ththate selective translation of influenzaviral mRNAs in infected cells occurred in a cap-dependent manner and was due at least in part to structures inherent in the mRNAs

  • Unlike the selective translular mRNA-secreted embryonic alkaline phosphatase lationmechanismsinvoked by poliovirus andadenovirus, replaced the nucleocapsid protein 5’-UTR, viral protein synthesis was inhibited in virus-infected cells, resembling host protein synthesis

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Summary

Introduction

Subjects otherwise stable and functional mRNAs already in the cytoplasm toblock at both the initiation and elongation stoefps translation (Katze et al, 1986). (iv) It encodes mRNAs with structural features that promote selective translation Using this assay we determined that during influenza virus infection, protein synthesis from exogenously introduced cellular genes was subject to the host cell shutoff.

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