数字农科院2.0

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

文献类型： 外文期刊

作者： Niu, Xinxin;Han, Jinze;Huang, Mengmeng;Wang, Guodong;Zhang, Yulong;Zhang, Wenying;Yu, Hangbo;Xu, Mengmeng;Li, Kai;Gao, Li;Wang, Suyan;Chen, Yuntong;Cui, Hongyu;Zhang, Yanping;Liu, Changjun;Wang, Xiaomei;Gao, Yulong;Qi, Xiaole

作者机构：

关键词： host shutoff;nucleocytoplasmic transport;Ran;RanBP1;infectious bursal disease virus

期刊名称： MBIO

ISSN： 2150-7511

年卷期： 2024 年

页码：

收录情况： SCIE（2024版）

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

分类号：

  • 相关文献

[1]通过RNA干扰技术研究Ran在褐飞虱发育和繁殖中的作用. 李凯龙,王渭霞,万品俊,赖凤香,傅强. 2015

[2]植物GTP结合蛋白的研究进展. 叶帅,朱正歌,缪军. 2008

[3]SAD2 functions in plant pathogen Pseudomonas syringae pv tomato DC3000 defense by regulating the nuclear accumulation of MYB30 in Arabidopsis thaliana. Tiantian Shi,Yuan Zheng,Rui Wang,Sha Li,Andi Xu,Luoying Chen,Yuanhang Liu,Rong Luo,Chenchen Huang,Yinglu Sun,Jinfeng Zhao,Xiaoying Guo,Huan Wang,Jun Liu,Ying Gao. 2024

[4]VP3 protein of Senecavirus A promotes viral IRES-driven translation and attenuates innate immunity by specifically relocalizing hnRNPA2B1. Li, Lu,Li, Xinwei,Zhong, Han,Li, Mingyang,Wan, Bo,He, Wenrui,Zhang, Yuhang,Du, Yongkun,Chen, Dongjie,Zhang, Wei,Ji, Pengchao,Jiang, Dawei,Han, Shichong. 2024

[5]Mapping of conformational epitopes on capsid protein VP2 of infectious bursal disease virus by fd-tet phage display. Cui, XL,Nagesha, HS,Holmes, IH. 2003

[6]Adjuvant effects of interleukin-18 in DNA vaccination against infectious bursal disease virus in chickens. Li, Kai,Gao, Honglei,Gao, Li,Qi, Xiaole,Gao, Yulong,Qin, Liting,Wang, Yongqiang,Wang, Xiaomei. 2013

[7]Reduction of infectious bursal disease virus replication by shRNAs targeting the VP1 and VP2 genes driven by chicken U6 promoter. Wei Ouyang,Ma, Jin-rong,Jiang, Jie-yuan,Wang, Yong-shan,Wang, Yong-qiang,Qin, Li-ting,Wang, Xiao-mei,Fan, Hong-jie. 2013

[8]Interaction of infectious bursal disease virus with the immune system of poultry. Rehman, Z. U.,Meng, C.,Ding, C.,Rehman, Z. U.,Umar, S.,Umar, S.,Munir, M..

[9]An improved method for infectious bursal disease virus rescue using RNA polymerase II system. Qi, Xiaole,Gao, Wong,Gao, Honglei,Deng, Xiaoyun,Bu, Zhigao,Wang, Xiaoyan,Fu, Chaoyang,Wang, Xiaomei. 2007

[10]Virus-like particles of hepatitis B virus core protein containing five mimotopes of infectious bursal disease virus (IBDV) protect chickens against IBDV. Wang, Yong-shan,Ouyang, Wei,Liu, Xiao-juan,He, Kong-wang,Liu, Xiao-juan,Zhang, Hai-bin,Fan, Hong-jie,Lu, Cheng-ping,Yu, Sheng-qing. 2012

[11]Exchange of the VP5 of infectious bursal disease virus in a serotype I strain with that of a serotype II strain reduced the viral replication and cytotoxicity. Qin, Liting,Qi, Xiaole,Gao, Honglei,Gao, Yulong,Bu, Zhigao,Wang, Xiaomei. 2009

[12]Codon optimization and woodchuck hepatitis virus posttranscriptional regulatory element enhance the immune responses of DNA vaccines against infectious bursal disease virus in chickens. Li, Kai,Gao, Li,Gao, Honglei,Qi, Xiaole,Gao, Yulong,Qin, Liting,Wang, Yongqiang,Wang, Xiaomei.

[13]Identification of crucial residues of conformational epitopes on VP2 protein of infectious bursal disease virus by phage display. Cui, XL,Nagesha, HS,Holmes, IH.

[14]Molecular characteristics of segment B of seven very virulent infectious bursal disease viruses isolated in china. Yu, Fei,Qi, Xiaole,Yuwen, Yanqing,Wang, Yongqiang,Gao, Honglei,Gao, Yulong,Qin, Litin,Wang, Xiaomei. 2010

[15]Comparative study of the replication of infectious bursal disease virus in DF-1 cell line and chicken embryo fibroblasts evaluated by a new real-time RT-PCR. Wang, Yongqiang,Qi, Xiaole,Gao, Honglei,Gao, Yulong,Lin, Huan,Song, Xiuqing,Pei, Lei,Wang, Xiaomei.

[16]Molecular characteristics and evolutionary analysis of a very virulent infectious bursal disease virus. Li Zan,Zhu Ping,Qi XiaoLe,Ren XianGang,Wang XiaoMei,Cui Lei,Li Zan. 2015

[17]Changes in VP3 and VP5 genes during the attenuation of the very virulent infectious bursal disease virus strain Gx isolated in China. Wang, Xiaomei,Zhang, Houshuang,Gao, Honglei,Fu, Chaoyang,Gao, Yulong,Ju, Yulin. 2007

[18]A single amino acid in the C-terminus of VP3 protein influences the replication of attenuated infectious bursal disease virus in vitro and in vivo. Wang, Yongqiang,Qi, Xiaole,Kang, Zhonghui,Yu, Fei,Qin, Liting,Gao, Honglei,Gao, Yulong,Wang, Xiaomei. 2010

[19]Recombinant infectious bursal disease virus expressing Newcastle disease virus (NDV) neutralizing epitope confers partial protection against virulent NDV challenge in chickens. Li, Kai,Gao, Li,Gao, Honglei,Qi, Xiaole,Gao, Yulong,Qin, Liting,Wang, Yongqiang,Wang, Xiaomei.

[20]Ribosomal protein L4 interacts with viral protein VP3 and regulates the replication of infectious bursal disease virus. Chen, Yuming,Lu, Zhen,Zhang, Lizhou,Gao, Li,Wang, Nian,Gao, Xiang,Wang, Yongqiang,Li, Kai,Gao, Yulong,Cui, Hongyu,Gao, Honglei,Liu, Changjun,Zhang, Yanping,Qi, Xiaole,Wang, Xiaomei,Wang, Xiaomei.

作者其他论文 更多>>