Enterovirus 71 inhibits cytoplasmic stress granule formation during the late stage of infection

• Published in: Virus research Vol. 255; pp. 55 - 67
• Main Authors: Zhang, Yating, Yao, Lili, Xu, Xin, Han, Huansheng, Li, Pengfei, Zou, Dehua, Li, Xingzhi, Zheng, Liang, Cheng, Lixin, Shen, Yujiang, Wang, Xianhe, Wu, Xuening, Xu, Jiaxin, Song, Baifen, Xu, Shuyan, Zhang, Hua, Cao, Hongwei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2018
• Subjects: 3C Viral Proteases; Arsenites - toxicity; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; cytopathogenicity; Cytoplasm - metabolism; cytoplasmic granules; Cytoplasmic Granules - enzymology; Cytoplasmic Granules - metabolism; Cytoplasmic Granules - virology; Disassemble; DNA Helicases - genetics; DNA Helicases - metabolism; Enterovirus 71; Enterovirus A; Enterovirus A, Human - metabolism; Enterovirus A, Human - physiology; Enterovirus Infections - metabolism; Enterovirus Infections - pathology; Enterovirus Infections - virology; G3BP1; Gene Expression; gene overexpression; HeLa Cells; Host-Pathogen Interactions; Humans; mitosis; Poly-ADP-Ribose Binding Proteins - genetics; Poly-ADP-Ribose Binding Proteins - metabolism; proteinases; RNA; RNA Helicases - genetics; RNA Helicases - metabolism; RNA Recognition Motif Proteins - genetics; RNA Recognition Motif Proteins - metabolism; Stress granules; stress response; Stress, Physiological - drug effects; Stress, Physiological - physiology; TIA1; translation (genetics); viral load; Viral Proteins - genetics; Viral Proteins - metabolism; Virus Replication; Enterovirus 71; TIA1; Disassemble; Stress granules; G3BP1
• ISSN: 0168-1702; 1872-7492; 1872-7492
• DOI: 10.1016/j.virusres.2018.07.006

•Protease 2Apro triggers SG formation at early EV71 infection stage.•Disruption of SGs is caused by EV71 protease 3Cpro-mediated G3BP1 cleavage.•G3BP1-positve SGs negatively regulate EV71 replication.•This study helps us to better understand the mechanism how EV71 interacts with the SG response. Stress granules (SGs) are host translationally silent ribonucleo-proteins formed in cells in response to multiple types of environmental stress, including viral infection. We previously showed that the nuclear protein, 68-kDa Src-associated in mitosis protein (Sam68), is recruited to cytoplasm and form the Sam68-positive SGs at 6 hpi, but the Sam68-positive SGs disassembled beyond 12 hpi, suggesting that the SGs might be inhibited during the late stage of Enterovirus 71 (EV71) infection. However, the mechanism and function of this process remains poorly understood. Thus in this study, we demonstrated that EV71 initially induced SGs formation at the early stage of EV71 infection, and confirmed that 2Apro of EV71 was the key viral component that triggered SG formation. In contrast, SGs were diminished as EV71 infection proceeding. At the same time, arsenite-induced SGs were also blocked at the late stage of EV71 infection. This disruption of SGs was caused by viral protease 3Cpro-mediated G3BP1 cleavage. Furthermore, we demonstrated that over-expression of G3BP1-SGs negatively impacted viral replication at the cytopathic effect (CPE), protein, RNA, and viral titer levels. Our novel finding may not only help us to better understand the mechanism how EV71 interacts with the SG response, but also provide mechanistic linkage between cellular stress responses and innate immune activation during EV71 infection.