Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy

Fanghang Zhou; Qianya Wan; Jing Lu; Ying Chen; Gui Lu; Ming-Liang He

doi:10.1016/j.isci.2019.08.008

Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy

iScience. 2019 Sep 27:19:715-727. doi: 10.1016/j.isci.2019.08.008. Epub 2019 Aug 8.

Authors

Fanghang Zhou¹, Qianya Wan¹, Jing Lu², Ying Chen¹, Gui Lu³, Ming-Liang He⁴

Affiliations

¹ Department of Biomedical Science, City University of Hong Kong, Kowloon, 1A-202, 2/F, Block 1, To Yuen Building, Hong Kong, 518000, China.
² Guangdong Provincial Institution of Public Health, Guangdong Center for Disease Control and Prevention, Guangzhou 510440, China.
³ School of Pharmacology, Sun Yat-sen University, Guangzhou, China.
⁴ Department of Biomedical Science, City University of Hong Kong, Kowloon, 1A-202, 2/F, Block 1, To Yuen Building, Hong Kong, 518000, China; CityU Shenzhen Research Institute, Nanshan, Shenzhen, China. Electronic address: mlhe7788@gmail.com.

Abstract

Enterovirus A71 (EV-A71) infection causes hand-foot-and-mouth disease (HFMD) and fatal neurological diseases, and there are no effective treatments. Host factors play key roles in establishing viral infection and determining the disease progression and outcome of antiviral therapies. In this study, we found that the expression of Pim1 was significantly upregulated in EV-A71 infection. Ectopic expression or silencing of Pim1 promoted or inhibited EV-A71 replication through two distinct mechanisms. Pim1 enhanced viral IRES activity by increasing viral 2A protease-mediated eIF4G cleavage and blocked AUF1, a suppressor of IRES, translocation from the nucleus to cytosol. More importantly, we discovered that Pim1 inhibitors (SGI-1776, AZD-1208, and CX-6258) reduced EV-A71 reproduction. Particularly, CX-6258 remarkably reduced EV-A71 reproduction more than 1,000 times, providing a potential therapeutic agent for EV-A71 treatment.

Keywords: Biochemistry; Biological Sciences; Cell Biology; Microbiology; Molecular Microbiology; Viral Microbiology; Virology.