tetano
Editor, Senior Moderator
Biosaf Health
. 2025 May 17;7(3):199-208.
doi: 10.1016/j.bsheal.2025.05.005. eCollection 2025 Jun. IncRNA IPAN antagonizes RIG-I/TRIM25-mediated degradation of influenza A virus PB1 to promote viral replication
Tingting Sun[SUP] 1 [/SUP], Shumin Chen[SUP] 1 2 [/SUP], Rui Zhou[SUP] 1 [/SUP], Saisai Guo[SUP] 1 [/SUP], Yilu Ye[SUP] 1 [/SUP], Jingyi Qiu[SUP] 1 [/SUP], Xiaoyu Li[SUP] 1 [/SUP], Shan Cen[SUP] 1 [/SUP], Jing Wang[SUP] 1 [/SUP]
Affiliations
The productive infection of influenza A virus (IAV) requires the functional involvement of host long noncoding ribonucleic acids (lncRNAs). Identification of key cellular lncRNAs and elucidation of their molecular mechanisms in IAV replication are expected to expand our understanding of virus-host interactions and develop antiviral therapeutics. Our previous work has identified that influenza virus polymerase basic protein 1 (PB1)-associated long noncoding RNA (IPAN) associates with and stabilizes viral RNA-dependent RNA polymerase PB1 of IAV, warranting efficient viral RNA synthesis. This provides a unique viral strategy of co-opting host lncRNA for replication, whereas the molecular pathways exploited by the virus are unknown. Here, we aim to further investigate the detailed mechanisms underlying IPAN-mediated PB1 stabilization. We employed cellular-level molecular interaction techniques to demonstrate that both retinoic acid-inducible gene I (RIG-I) and tripartite motif-containing protein 25 (TRIM25) interacted with PB1 and co-operated to induce its degradation triggered by viral RNA synthesis. The experimental data obtained from RIG-I knockout cell lines and mutational analyses demonstrated RIG-I promoted PB1 degradation independently of its canonical signaling pathway, suggesting an "effector-like" antiviral activity of RIG-I. Furthermore, IPAN knockdown enhanced the association of PB1 with both RIG-I and TRIM25 to restore PB1 stability. These results collectively demonstrated that IAV hijacked host IPAN to protect PB1 from RIG-I/TRIM25-mediated antiviral degradation. Thus, our data reveal a mechanism of RIG-I and TRIM25 against IAV infection by degrading PB1 and highlight how IAV exploits host lncRNAs to evade immune surveillance.
Keywords: Degradation; Influenza A virus (IAV); Influenza virus PB1-associated long noncoding RNA (IPAN); Innate immunity; Long noncoding ribonucleic acids (lncRNAs); Retinoic acid-inducible gene I (RIG-I); Tripartite motif-containing protein 25 (TRIM25).
. 2025 May 17;7(3):199-208.
doi: 10.1016/j.bsheal.2025.05.005. eCollection 2025 Jun. IncRNA IPAN antagonizes RIG-I/TRIM25-mediated degradation of influenza A virus PB1 to promote viral replication
Tingting Sun[SUP] 1 [/SUP], Shumin Chen[SUP] 1 2 [/SUP], Rui Zhou[SUP] 1 [/SUP], Saisai Guo[SUP] 1 [/SUP], Yilu Ye[SUP] 1 [/SUP], Jingyi Qiu[SUP] 1 [/SUP], Xiaoyu Li[SUP] 1 [/SUP], Shan Cen[SUP] 1 [/SUP], Jing Wang[SUP] 1 [/SUP]
Affiliations
- PMID: 40693041
- PMCID: PMC12276541
- DOI: 10.1016/j.bsheal.2025.05.005
The productive infection of influenza A virus (IAV) requires the functional involvement of host long noncoding ribonucleic acids (lncRNAs). Identification of key cellular lncRNAs and elucidation of their molecular mechanisms in IAV replication are expected to expand our understanding of virus-host interactions and develop antiviral therapeutics. Our previous work has identified that influenza virus polymerase basic protein 1 (PB1)-associated long noncoding RNA (IPAN) associates with and stabilizes viral RNA-dependent RNA polymerase PB1 of IAV, warranting efficient viral RNA synthesis. This provides a unique viral strategy of co-opting host lncRNA for replication, whereas the molecular pathways exploited by the virus are unknown. Here, we aim to further investigate the detailed mechanisms underlying IPAN-mediated PB1 stabilization. We employed cellular-level molecular interaction techniques to demonstrate that both retinoic acid-inducible gene I (RIG-I) and tripartite motif-containing protein 25 (TRIM25) interacted with PB1 and co-operated to induce its degradation triggered by viral RNA synthesis. The experimental data obtained from RIG-I knockout cell lines and mutational analyses demonstrated RIG-I promoted PB1 degradation independently of its canonical signaling pathway, suggesting an "effector-like" antiviral activity of RIG-I. Furthermore, IPAN knockdown enhanced the association of PB1 with both RIG-I and TRIM25 to restore PB1 stability. These results collectively demonstrated that IAV hijacked host IPAN to protect PB1 from RIG-I/TRIM25-mediated antiviral degradation. Thus, our data reveal a mechanism of RIG-I and TRIM25 against IAV infection by degrading PB1 and highlight how IAV exploits host lncRNAs to evade immune surveillance.
Keywords: Degradation; Influenza A virus (IAV); Influenza virus PB1-associated long noncoding RNA (IPAN); Innate immunity; Long noncoding ribonucleic acids (lncRNAs); Retinoic acid-inducible gene I (RIG-I); Tripartite motif-containing protein 25 (TRIM25).