<i>N</i> 6-methyladnosine of vRNA facilitates influenza A virus replication by promoting the interaction of vRNA with polymerase proteins
Abstract
N 6-methyladnosine (m 6 A) modification is present in both positive- and negative-strand RNA of influenza A virus (IAV) and affects the replication and pathogenicity of IAV. However, little is known about the regulatory mechanism of m 6 A in IAV RNA. In the present study, we identified the m 6 A methylation of the viral RNA of different IAV subtypes and confirmed that m 6 A modification promotes the polymerase activity and replication of IAV. By mutating m 6 A motifs on the multiple viral RNAs (vRNAs) of IAV, we revealed that m 6 A deficiency in vRNA suppresses the expression of viral genes and the replication of the virus in vitro. In addition, m 6 A deficiency in vRNA reduced the pathogenicity of IAV in a mouse model. Mechanistically, m 6 A deficiency in vRNA suppresses the assembly of the viral ribonucleoprotein (vRNP) complex by impairing the interaction between vRNA and vRNP proteins in an m 6 A methyltransferase-dependent manner, but not the m 6 A reader proteins. Together, our findings reveal an important role for m 6 A on viral RNAs in facilitating the activity of the polymerase complex and the replication and pathogenicity of IAV, which provides insights for the development of novel anti-influenza strategies.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (12)
Qian Wang
Shuai Xu
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Wentao Shen
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Yanli Wei
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Lu Han
School of Chemical Science and Engineering, Tongji University, 1239 Siping Road, Shanghai 200092, China
Zhengxiang Wang
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Yingying Yu
Tempus AI, Inc.
Minxuan Liu
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Junwen Liu
Institute for Environmental and Climate Research, College of Environment and Climate, Jinan University
Guohua Deng
State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Hualan Chen
State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences
Qiyun Zhu
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences