Protease 2A induces stress granule formation during coxsackievirus B3 and enterovirus 71 infections

Virology Journal

Zhaohua Zhong¹  Wenran Zhao²  Fengmin Zhang¹  Xiaoyu Li³  Yang Chen¹  Ying Luan¹  Lei Tong¹  Xiaoyan Zhong¹  Tianying Wang¹  Xiaoning Si¹  Lexun Lin¹  Yan Wang¹  Shuo Wu¹ 

[1] Department of Microbiology, Harbin Medical University, Harbin 150081, China;Department of Cell Biology, Harbin Medical University, Harbin 150081, China;Division of Gastroenterology and Hepatology, Department of Medicine, University of Florida-Jacksonville, Jacksonville 32206, FL, USA

关键词: Enterovirus 71;    Coxsackievirus B;    2A protease;    Stress granule;   

Others  :  1148128
DOI  :  10.1186/s12985-014-0192-1

 received in 2014-04-12, accepted in 2014-10-26,  发布年份 2014

【 摘 要 】

Background

Stress granules (SGs) are granular aggregates in the cytoplasm that are formed under a variety of stress situations including viral infection. Previous studies indicate that poliovirus, a member of Picornaviridae, can induce SG formation. However, the exact mechanism by which the picornaviruses induce SG formation is unknown.

Method

The localization of SG markers in cells infected with coxsackievirus B3 (CVB3) or enterovirus 71 (EV71) and in cells expressing each viral protein was determined via immunofluorescence assays or plasmid transfection. Eight plasmids expressing mutants of the 2A protease (2A^pro) of CVB3 were generated using a site-directed mutagenesis strategy. The cleavage efficiencies of eIF4G by CVB3 2A^pro and its mutants were determined via western blotting assays.

Results

In this study, we found that CVB3 infection induced SG formation, as evidenced by the co-localization of some accepted SG markers in viral infection-induced granules. Furthermore, we identified that 2A^pro of CVB3 was the key viral component that triggered SG formation. A 2A^pro mutant with the G122E mutation, which exhibited very low cleavage efficiency toward eIF4G, significantly attenuated its capacity for SG induction, indicating that the protease activity was required for 2A^pro to initiate SG formation. Finally, we observed that SGs also formed in EV71-infected cells. Expression of EV71 2A^pro alone was also sufficient to cause SG formation.

Conclusion

Both CVB3 and EV71 infections can induce SG formation, and 2A^pro plays a crucial role in the induction of SG formation during these infections. This finding may help us to better understand how picornaviruses initiate the SG response.

【 授权许可】

   
2014 Wu et al.; licensee BioMed Central Ltd.

【 图 表 】

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