Influences of Ns2 on Influenza Viral Production through Its Post-Translational Modification

Influenza A viruses (IAV) causes influenza and global pandemics. This virus encodes a nonstructural protein, NS2, which critically affects IAV’s production and adaptation of avian IAV to human. NS2 is expressed at a low level, but gradually accumulates. The accumulation is thought to cause a transcription-replication switch and nuclear export of viral ribonucleoproteins (vRNPs). As IAV uses the same vRNA promoter for the transcription of vRNA for mRNA and cRNA synthesis, the transcription is mutually exclusive. At the initial stage of the infection, the promoter is used only for mRNA synthesis. As NS2 gradually accumulates, the transcription shifts to cRNA synthesis. It is also known that NS2 interacts with PB2, which is a component of RNA-dependent RNA polymerase involved in cap snatching from nascent cellular mRNA for initiation of IAV mRNA synthesis. This study proposes that PB2’s cap snatching ability is inhibited after its interaction with NS2, allowing the promoter to transcribe only cRNA. This study also hypothesizes that SUMOylation affects NS2’s ability to interact with PB2, M1, and Crm1 to attenuate mRNA synthesis and promotes nuclear export of vRNPs. This study will investigate whether NS2’s SUMOylation and ubiquitination influence IAV’s mRNA and cRNA syntheses, the nuclear export of vRNP, and IAV’s production. The studies will improve our understanding on the functions of one of the most important IAV proteins, NS2.

Project ID:PC10907-1005
External Project ID:MOST109-2320-B182-028-MY3