Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner

• DOI: 10.1128/mbio.03433-23
• Publication Date: 2024-01-30T14:01:14Z
• Authors: Xinxin Niu; Jinze Han; Mengmeng Huang; Guodong Wang; Yulong Zhang; Wenying Zhang; Hangbo Yu; Mengmeng Xu; Kai Li; Li Gao; Suyan Wang; Yuntong Chen; Hongyu Cui; Yanping Zhang; Changjun Liu; Xiaomei Wang; Yulong Gao; Xiaole Qi
• Keywords: Infectious bursal disease

ABSTRACT Viruses have evolved intricate mechanisms to evade host antiviral responses and exploit cellular resources by manipulating the expression profile of genes. During infection, viruses encode proteins with shutoff activity globally inhibit protein synthesis, which is an effective strategy for immune evasion. In this study, compelling evidence shows that infectious bursal disease virus (IBDV) infection triggers suppression synthesis. Furthermore, using both in vitro vivo viral models, we identified IBDV specifically impedes transcription genes via VP5, simultaneously conferring advantages these circumstances. The proposed mechanism suggests VP5 competitively binds RanBP1, disrupting RanGDP/GTP gradient. This disruption interferes nucleocytoplasmic transport, impairing nuclear import bearing localization signals. transport pivotal transcriptional regulatory factors, such as p65 IFN factor 7, also compromised, leading inhibition pro-inflammatory cytokines interferon expression. newly discovered employed enables them manipulate gene expression, providing novel insights into how establish infections. IMPORTANCE processes at various levels regulate or innate adaptive responses, promoting self-survival efficient transmission. “host shutoff,” a global mediated viruses, considered critical evading immunity. validated presence during additionally uncovered plays role inhibiting overall synthesis proteins, including cytokines, through transcription-dependent pathway. Ran cycle consequently interfering ultimately results transcription. These findings unveil immunity rapidly infection. study supplement understanding pathway