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J Virol. Influenza C virus NS1 protein up-regulates the splicing of viral mRNAs.

Giuseppe

Emeritus
J Virol.. [Epub ahead of print]

Influenza C virus NS1 protein up-regulates the splicing of viral mRNAs.

Muraki Y, Furukawa T, Kohno Y, Matsuzaki Y, Takashita E, Sugawara K, Hongo S. - Department of Infectious Diseases, Yamagata University Faculty of Medicine, Iida-Nishi, Yamagata 990-9585, Japan; Drug analysis Department, Kashima Laboratory, Toxicological Science Division, Medi-Chem Business Segment, Mitsubishi Chemical Medience Corporation, Sunayama 14, Kamisu-city, Ibaraki, 314-0255, Japan; Influenza Virus Research Center, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan.

Pre-mRNAs of the influenza A virus M and NS genes are poorly spliced in virus-infected cells. By contrast, in influenza C virus-infected cells, the predominant transcript from the M gene is spliced mRNA. The present study was performed to investigate the mechanism by which influenza C virus M gene-specific mRNA (M mRNA) is readily spliced. The ratio of M1 encoded by a spliced M mRNA to CM2 encoded by an unspliced M mRNA in influenza C virus-infected cells was about 10 times larger than that in M gene-transfected cells, suggesting that viral protein(s) other than M gene-translational products facilitates viral mRNA splicing. Ribonuclease protection assays showed that the splicing of M mRNA in infected cells was much higher than that in M gene-transfected cells. The unspliced and spliced mRNAs of the influenza C virus NS gene encode two nonstructural (NS) proteins, NS1(C/NS1) and NS2(C/NS2), respectively. The introduction of translational premature termination into the NS gene, which blocked the synthesis of C/NS1 and C/NS2 proteins, drastically reduced the splicing of NS mRNA, raising the possibility that C/NS1 or C/NS2 enhances viral mRNA splicing. The splicing of influenza C virus M mRNA was increased by co-expression of C/NS1, whereas it was reduced by co-expression of influenza A virus NS1 protein (A/NS1). The splicing of influenza A virus M mRNA was also increased by co-expression of C/NS1, though it was inhibited by that of A/NS1. These results suggest that influenza C virus NS1, but not A/NS1, can up-regulate viral mRNA splicing.

PMID: 20007279 [PubMed - as supplied by publisher]

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