Influenza C virus NS1 protein upregulates the splicing of viral mRNAs.
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 a viral protein(s) other than M gene translational products facilitates viral mRNA splicing. RNase 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 premature translational termination into the NS gene, which blocked the synthesis of the 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 coexpression of C/NS1, whereas it was reduced by coexpression of the influenza A virus NS1 protein (A/NS1). The splicing of influenza A virus M mRNA was also increased by coexpression 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 upregulate viral mRNA splicing.
Muraki
Yasushi
Y
Department of Infectious Diseases, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Furukawa
Takatoshi
T
Kohno
Yoshihiko
Y
Matsuzaki
Yoko
Y
Takashita
Emi
E
Sugawara
Kanetsu
K
Hongo
Seiji
S
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D005814:Genes, Viral; D006801:Humans; D009982:Gammainfluenzavirus / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D012326:RNA Splicing / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; C085820:INS1 protein, influenza virus; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; D017361:Viral Nonstructural Proteins