tetano
Editor, Senior Moderator
J Virol
. 2023 Dec 6:e0116623.
doi: 10.1128/jvi.01166-23. Online ahead of print. Twenty natural amino acid substitution screening at the last residue 121 of influenza A virus NS2 protein reveals the critical role of NS2 in promoting virus genome replication by coordinating with viral polymerase
Lei Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuekun Shao[SUP] #[/SUP][SUP] 1 3 [/SUP], Yingying Wang[SUP] 1 [/SUP], Qiuxian Yang[SUP] 1 [/SUP], Jiamei Guo[SUP] 1 [/SUP], George F Gao[SUP] 1 3 [/SUP], Tao Deng[SUP] 1 3 [/SUP]
Affiliations
The intrinsic mechanisms of influenza RNA polymerase (FluPol) in catalyzing viral genome transcription and replication have been largely resolved. However, the mechanisms of how transcription and replication are dynamically regulated remain elusive. We recently reported that the last amino acid of the viral NS2 protein plays a critical role in promoting viral genome replication in an influenza mini-replicon system. Here, we conducted a 20 amino acid substitution screening at the last residue 121 in virus rescue and serial passage. Our results demonstrate that the replication-promoting function of NS2 is important for virus survival and efficient multiplication. We further show evidence that NS2 and NS2-I[SUB]121[/SUB] adaptive mutations PA-K19E/PB1-S713N regulate virus genome replication by promoting FluPol dimerization. This work highlights the coordination between NS2 and FluPol in fulfilling efficient genome replication. It further advances our understanding of the regulation of viral RNA synthesis for influenza A virus.
Keywords: FluPol; NS2; adaptive mutations; influenza virus; virus genome transcription and replication.
. 2023 Dec 6:e0116623.
doi: 10.1128/jvi.01166-23. Online ahead of print. Twenty natural amino acid substitution screening at the last residue 121 of influenza A virus NS2 protein reveals the critical role of NS2 in promoting virus genome replication by coordinating with viral polymerase
Lei Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], Yuekun Shao[SUP] #[/SUP][SUP] 1 3 [/SUP], Yingying Wang[SUP] 1 [/SUP], Qiuxian Yang[SUP] 1 [/SUP], Jiamei Guo[SUP] 1 [/SUP], George F Gao[SUP] 1 3 [/SUP], Tao Deng[SUP] 1 3 [/SUP]
Affiliations
- PMID: 38054704
- DOI: 10.1128/jvi.01166-23
The intrinsic mechanisms of influenza RNA polymerase (FluPol) in catalyzing viral genome transcription and replication have been largely resolved. However, the mechanisms of how transcription and replication are dynamically regulated remain elusive. We recently reported that the last amino acid of the viral NS2 protein plays a critical role in promoting viral genome replication in an influenza mini-replicon system. Here, we conducted a 20 amino acid substitution screening at the last residue 121 in virus rescue and serial passage. Our results demonstrate that the replication-promoting function of NS2 is important for virus survival and efficient multiplication. We further show evidence that NS2 and NS2-I[SUB]121[/SUB] adaptive mutations PA-K19E/PB1-S713N regulate virus genome replication by promoting FluPol dimerization. This work highlights the coordination between NS2 and FluPol in fulfilling efficient genome replication. It further advances our understanding of the regulation of viral RNA synthesis for influenza A virus.
Keywords: FluPol; NS2; adaptive mutations; influenza virus; virus genome transcription and replication.