ABSTRACT Influenza C virus possesses a unique M gene coding strategy. Whereas unspliced and spliced mRNAs from influenza A virus RNA segment 7 (M gene) encode matrix protein M1 and proton channel protein M2, respectively, spliced and unspliced mRNAs from influenza C virus RNA segment 6 (M gene) encode matrix protein M1 and a 374-amino-acid protein, designated P42, respectively. Influenza C virus M1 affects virion morphology. P42 is cleaved by signal peptidase to generate CM2, which can form a chloride-selective ion channel. The CM2 molecule plays a role in the genome packaging and uncoating processes of the virus replication cycle. The unspliced and spliced mRNAs of influenza C virus NS gene encode NS1 and NS2, the latter of which plays a role in the nuclear export of vRNPs. Whereas the pre-mRNAs of the influenza A virus M and NS genes are poorly spliced in virus-infected cells, the predominant transcript from influenza C virus M gene is spliced mRNA. The mechanism by which influenza C virus M gene-specific mRNA (M mRNA) is readily spliced can be explained as follows. Influenza C virus NS1 can up-regulate the splicing of viral mRNAs, including influenza C virus M and NS mRNAs, whereas influenza A virus NS1 down-regulates mRNA splicing. Therefore, we speculate that influenza C virus NS1, which enhances the splicing of viral mRNAs, may regulate both the expression level of M gene-derived M1 and CM2 proteins as well as that of NS gene-derived NS1 and NS2 proteins, thereby leading to optimal virus replication.
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