TRIM41-Mediated Ubiquitination of Nucleoprotein Limits Influenza A Virus Infection

作者：Girish Patil, Mengmeng Zhao, Kun Song, Wenzhuo Hao, Daniel Bouchereau, Lingyan Wang, Shitao Li · 发表于：Journal of Virology · 年份：2018 · DOI：10.1128/jvi.00905-18 · 被引用次数：91 · 研究领域：interferon and immune responses、Influenza Virus Research Studies、Ubiquitin and proteasome pathways

Influenza control strategies rely on annual immunization and require frequent updates of the vaccine, which is not always a foolproof process. Furthermore, the current antivirals are also losing effectiveness as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new antiviral mechanisms and develop therapeutic drugs based on these mechanisms. Targeting the virus-host interface is an emerging new strategy because host factors controlling viral replication activity will be ideal candidates, and cellular proteins are less likely to mutate under drug-mediated selective pressure. Here, we show that the ubiquitin E3 ligase TRIM41 is an intrinsic host restriction factor to IAV. TRIM41 directly binds the viral nucleoprotein and targets it for ubiquitination and proteasomal degradation, thereby limiting viral infection. Exploitation of this natural defense pathway may open new avenues to develop antiviral drugs targeting the influenza virus.