数字农科院2.0

Hnrnp K Is A Novel Internal Ribosomal Entry Site-Transacting Factor That Negatively Regulates Foot-And-Mouth Disease Virus Translation And Replication And Is Antagonized By Viral 3C Protease

文献类型： 外文期刊

作者： Liu, WM; Yang, DC; Sun, C; Wang, HW; Zhao, B; Zhou, GH; Yu, L

作者机构：

关键词： Foot-And-Mouth Disease Virus; Heterogeneous Nuclear Ribonucleoprotein K; Internal Ribosomal Entry Site; Translational Regulation; Virus-Host Interactions

期刊名称： JOURNAL OF VIROLOGY

ISSN： 0022-538X

年卷期： 2020 年 94 卷 17 期

页码：

收录情况： JCR（2021版）

摘要： Cap-independent translation initiation on picornavirus mRNAs is mediated by an internal ribosomal entry site (IRES) in the 5' untranslated region. The regulation of internal initiation requires the interaction of IRES-transacting factors (ITAFs) with the IRES. In this study, we identified a novel ITAF, heterogeneous nuclear ribonucleoprotein K (hnRNP K), which negatively regulates foot-and-mouth disease virus (FMDV) translation and viral replication. Further investigation revealed that the KH2 and KH3 domains of hnRNP K directly bind to domains II, III, and IV of the FMDV IRES, resulting in the inhibition of IRES-mediated translation by interfering with the recognition of another positive ITAF, polypyrimidine tract-binding protein (PTB). Conversely, hnRNP K-mediated inhibition was antagonized by the viral 3C protease through the cleavage of hnRNP K at the Glu-364 residue during FMDV infection. Interestingly, the N-terminal cleavage product, hnRNP K-1-(364) retained partial inhibitory effects on IRES activity, whereas the C-terminal cleavage product, hnRNP K364-465, became a positive regulator of FMDV replication. Our findings expand the current understanding of virus-host interactions concerning viral recruitment and the modulation of ITAFs, providing new insights into translational control during viral infection. IMPORTANCE The translation of picornaviral genome RNA mediated by the internal ribosomal entry site (IRES) is a crucial step for virus infections. Virus-host interactions play a critical role in the regulation of IRES-dependent translation, but the regulatory mechanism remains largely unknown. In this study, we identified an ITAF, hnRNP K, that negatively regulates FMDV replication by inhibiting viral IRES-mediated translation. In addition, we describe a novel translational regulation mechanism involving the proteolytic cleavage of hnRNP K by FMDV protease 3C. The cleavage of hnRNP K yields two cleavage products with opposite functions: the cleavage product hnRNP K1-364 retains a partial inhibitory effect on IRES activity, and the cleavage product hnRNP K-364(-)465 becomes a positive regulator of FMDV replication. Our findings shed light on the effect of a novel ITAF on the translational regulation of picornavirus and provide new insights into translational control during viral infection.

分类号：

  • 相关文献

[1]Identification of the largest non-essential regions of the C-terminal portion in 3A protein of foot-and-mouth disease virus for replication in cell culture. . 2020

[2]The Effects Of Nucleotide Usage I.n Key Nucleotide Positions+4 A nd-3 Flanking Start Codon On Translation Levels Mediated By Ires Of Hepatitis C Virus. Ma, P, Ma, XX, Chang, QY, Li, LJ, Wang, YN, Feng, YP, Ma, ZR, Zhou, JH. 2018

[3]Host Src Controls Gallid Alpha Herpesvirus 1 Intercellular Spread In A Cellular Fatty Acid Metabolism-Dependent Manner. Wang, ZT, Sun, BY, Gao, Q, Ma, Y, Liang, YM, Chen, ZJ, Wu, HG, Cui, L, Shao, YH, Wei, P, Li, H, Liu, SW. 2019

[4]Long Non-Coding Rnas: Emerging And V.ersatile Regulators In Host-Virus I nteractions. Meng, XY, Luo, YZ, Anwar, MN, Sun, Y, Gao, Y, Zhang, HW, Munir, M, Qiu, HJ. 2017

[5]Avian Flavivirus Infection Of Monocytes/Macrophages B.y Extensive Subversion Of H ost Antiviral Innate Immune Responses. Ma, Y, Liang, YM, Wang, NN, Cui, L, Chen, ZJ, Wu, HG, Zhu, CY, Wang, ZT, Liu, SW, Li, H. 2019

[6]Gallid Herpesvirus 1 Initiates Apoptosis I.n Uninfected Cells Through P aracrine Repression Of P53. Li, H, Gao, Q, Shao, YH, Sun, BY, Wang, FJ, Qiao, YY, Wang, NN, Liu, SW. 2018

[7]Ecological drivers and functional roles of phage communities in the Yangtze River’s freshwater ecosystems. Liang Peng, Fengxia Yang, Jing Zhang, Jiayu Shang, Wei Xu, Shoushan Sheng, Qinfen Li, Yukun Zou, Zhengfu Yue. 2025

[8]Establishment of a Murine alpha nu beta 1 Transgenic CHO-K1 Cell Line and its Susceptibility to Foot-and-Mouth Disease Virus Type Asia 1/HN/2006 in China. Zhang, Y.,Zheng, H. X.,Zhang, Z. D.,Jin, Y.,Yang, F.,He, J. J.,Cao, W. J.,Sun, D. H.,Lv, L.. 2013

[9]Induction of systemic IFITM3 expression does not effectively control foot-and-mouth disease viral infection in transgenic pigs. Zhang, Huawei,Qian, Ping,Xu, Jinfang,Yang, Xi,Zhou, Rui,Chen, Huanchun,Li, Xiangmin,Zhang, Huawei,Qian, Ping,Xu, Jinfang,Yang, Xi,Zhou, Rui,Chen, Huanchun,Li, Xiangmin,Zheng, Haixue.

[10]Effect of the nucleotides surrounding the start codon on the translation of foot-and-mouth disease virus RNA. Ma, X. X.,Feng, Y. P.,Ma, Z. R.,Gu, Y. X.,Ma, X. X.,Zhou, J. H..

[11]Protection of a novel epitope-RNA VLP double-effective VLP vaccine for foot-and-mouth disease. Dong, Yan-mei,Chen, Liang,Dong, Yan-mei,Cai, Jian-chun,Chen, Hao-tai.

[12]Foot-and-mouth disease virus structural protein VP3 degrades Janus kinase 1 to inhibit IFN-gamma signal transduction pathways. Li, Dan,Yang, Fan,Liu, Hua-Nan,Zhu, Zi-Xiang,Cao, Wei-Jun,Liu, Xiang-Tao,Zheng, Hai-Xue,Wei, Jin,Li, Shu,Shu, Hong-Bing.

[13]Swine interferon-induced transmembrane protein, sIFITM3, inhibits foot-and-mouth disease virus infection in vitro and in vivo. Xu, Jinfang,Qian, Ping,Wu, Qunfeng,Liu, Shasha,Fan, Wenchun,Wang, Rong,Zhang, Huawei,Chen, Huanchun,Li, Xiangmin,Xu, Jinfang,Qian, Ping,Wu, Qunfeng,Liu, Shasha,Fan, Wenchun,Wang, Rong,Zhang, Huawei,Chen, Huanchun,Li, Xiangmin,Zhang, Keshan. 2014

[14]Techniques developed in china for foot-and-mouth disease diagnosis. Lu, Z.,Cao, Y.,Bao, H.,Qi, S.,Guo, J.,Shang, Y.,Jiang, T.,Zhang, Q.,Ma, J.,Liu, Z.,Liu, X.,Yin, H.,Xie, Q.. 2008

[15]Recombinant adenovirus expressing type Asia1 foot-and-mouth disease virus capsid proteins induces protective immunity against homologous virus challenge in mice. Zhou, Guohui,Wang, Haiwei,Wang, Fang,Yu, Li.

[16]EFFECT OF THE ROUTE OF FOOT-AND-MOUTH DISEASE VIRUS INFECTION OF PIGLETS ON THE COURSE OF DISEASE. Li, D.,Bai, X. -W.,Sun, P.,Fu, Y. -F.,Xie, B. -X.,Lu, Z. -J.,Chen, Y. -L.,Cao, W. -J.,Liu, Z. -X.. 2010

[17]Determination of Cattle Foot-and-Mouth Disease Virus by Micro-ELISA Method. Dong, Yiyang,Xu, Yan,Xu, Yan,Mawatari, Kazuma,Kitamori, Takehiko,Liu, Zaixin,Fu, Yuanfang,Ohashi, Toshinori,Mawatari, Kazuma,Kitamori, Takehiko.

[18]Purification of foot-and-mouth disease virus by heparin as ligand for certain strains. Du, Ping,Sun, Shiqi,Dong, Jinjie,Zhi, Xiaoying,Chang, Yanyan,Teng, Zhidong,Guo, Huichen,Liu, Zaixin.

[19]The effects of the synonymous codon usage and tRNA abundance on protein folding of the 3C protease of foot-and-mouth disease virus. Zhou, Jian-hua,You, Ya-nan,Chen, Hao-tai,Zhang, Jie,Ma, Li-na,Ding, Yao-zhong,Liu, Yong-sheng,Pejsak, Zygmunt.

[20]A novel bi-functional DNA vaccine expressing VP1 protein and producing antisense RNA targeted to 5 ' UTR of foot-and-mouth disease virus can induce both rapid inhibitory effect and specific immune response in mice. Yang, Bin,Li, Yanmin,Zhang, Zhidong,Yang, Bin,Lan, Xi,Li, Xueri,Yin, Xiangping,Li, Baoyu,Han, Xiaorong,Li, Yanmin,Zhang, Zhidong,Liu, Jixing. 2008

作者其他论文 更多>>