tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2025 Mar 18;122(11):e2411554122.
doi: 10.1073/pnas.2411554122. Epub 2025 Mar 12. N 6-methyladnosine of vRNA facilitates influenza A virus replication by promoting the interaction of vRNA with polymerase proteins
Qian Wang[SUP] #[/SUP][SUP] 1 [/SUP], Shuai Xu[SUP] #[/SUP][SUP] 1 2 [/SUP], Wentao Shen[SUP] 1 [/SUP], Yanli Wei[SUP] 1 [/SUP], Lu Han[SUP] 1 [/SUP], Zhengxiang Wang[SUP] 1 [/SUP], Yingying Yu[SUP] 1 [/SUP], Minxuan Liu[SUP] 1 [/SUP], Junwen Liu[SUP] 1 [/SUP], Guohua Deng[SUP] 3 [/SUP], Hualan Chen[SUP] 3 [/SUP], Qiyun Zhu[SUP] 1 2 [/SUP]
Affiliations
N6-methyladnosine (m[SUP]6[/SUP]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[SUP]6[/SUP]A in IAV RNA. In the present study, we identified the m[SUP]6[/SUP]A methylation of the viral RNA of different IAV subtypes and confirmed that m[SUP]6[/SUP]A modification promotes the polymerase activity and replication of IAV. By mutating m[SUP]6[/SUP]A motifs on the multiple viral RNAs (vRNAs) of IAV, we revealed that m[SUP]6[/SUP]A deficiency in vRNA suppresses the expression of viral genes and the replication of the virus in vitro. In addition, m[SUP]6[/SUP]A deficiency in vRNA reduced the pathogenicity of IAV in a mouse model. Mechanistically, m[SUP]6[/SUP]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[SUP]6[/SUP]A methyltransferase-dependent manner, but not the m[SUP]6[/SUP]A reader proteins. Together, our findings reveal an important role for m[SUP]6[/SUP]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.
Keywords: N6-methyladenosine; influenza A virus; replication; viral RNA; viral ribonucleoprotein complex.
. 2025 Mar 18;122(11):e2411554122.
doi: 10.1073/pnas.2411554122. Epub 2025 Mar 12. N 6-methyladnosine of vRNA facilitates influenza A virus replication by promoting the interaction of vRNA with polymerase proteins
Qian Wang[SUP] #[/SUP][SUP] 1 [/SUP], Shuai Xu[SUP] #[/SUP][SUP] 1 2 [/SUP], Wentao Shen[SUP] 1 [/SUP], Yanli Wei[SUP] 1 [/SUP], Lu Han[SUP] 1 [/SUP], Zhengxiang Wang[SUP] 1 [/SUP], Yingying Yu[SUP] 1 [/SUP], Minxuan Liu[SUP] 1 [/SUP], Junwen Liu[SUP] 1 [/SUP], Guohua Deng[SUP] 3 [/SUP], Hualan Chen[SUP] 3 [/SUP], Qiyun Zhu[SUP] 1 2 [/SUP]
Affiliations
- PMID: 40073063
- DOI: 10.1073/pnas.2411554122
N6-methyladnosine (m[SUP]6[/SUP]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[SUP]6[/SUP]A in IAV RNA. In the present study, we identified the m[SUP]6[/SUP]A methylation of the viral RNA of different IAV subtypes and confirmed that m[SUP]6[/SUP]A modification promotes the polymerase activity and replication of IAV. By mutating m[SUP]6[/SUP]A motifs on the multiple viral RNAs (vRNAs) of IAV, we revealed that m[SUP]6[/SUP]A deficiency in vRNA suppresses the expression of viral genes and the replication of the virus in vitro. In addition, m[SUP]6[/SUP]A deficiency in vRNA reduced the pathogenicity of IAV in a mouse model. Mechanistically, m[SUP]6[/SUP]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[SUP]6[/SUP]A methyltransferase-dependent manner, but not the m[SUP]6[/SUP]A reader proteins. Together, our findings reveal an important role for m[SUP]6[/SUP]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.
Keywords: N6-methyladenosine; influenza A virus; replication; viral RNA; viral ribonucleoprotein complex.