Abstract
N6-methyladenosine (m6A) modification on viral RNAs has a profound impact on infectivity. m6A is also a highly pervasive modification for influenza viral RNAs. However, its role in virus mRNA splicing is largely unknown. Here, we identify the m6A reader protein YTHDC1 as a host factor that associates with influenza A virus NS1 protein and modulates viral mRNA splicing. YTHDC1 levels are enhanced by IAV infection. We demonstrate that YTHDC1 inhibits NS splicing by binding to an NS 3′ splicing site and promotes IAV replication and pathogenicity in vitro and in vivo. Our results provide a mechanistic understanding of IAV-host interactions, a potential therapeutic target for blocking influenza virus infection, and a new avenue for the development of attenuated vaccines.
Funder
Key Technologies Research and Development Program
National Natural Science Foundation of China
China Postdoctoral Science Foundation
Natural Science Foundation of Hubei Province
Earmarked fund
Publisher
Public Library of Science (PLoS)
Subject
Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology
Cited by
1 articles.
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