AIMP2 restricts EV71 replication by recruiting SMURF2 to promote the degradation of 3D polymerase

Junrui Ren; Lei Yu; Qiuhan Zhang; Pengyu Ren; Yumeng Cai; Xueyun Wang; Ke Lan; Shuwen Wu

doi:10.1016/j.virs.2024.06.009

August 2024

Citation: Junrui Ren, Lei Yu, Qiuhan Zhang, Pengyu Ren, Yumeng Cai, Xueyun Wang, Ke Lan, Shuwen Wu. AIMP2 restricts EV71 replication by recruiting SMURF2 to promote the degradation of 3D polymerase .VIROLOGICA SINICA, 2024, 39(4) : 632-644. http://dx.doi.org/10.1016/j.virs.2024.06.009

AIMP2 restricts EV71 replication by recruiting SMURF2 to promote the degradation of 3D polymerase

Junrui Ren ^a ,
Lei Yu ^a,b ,
Qiuhan Zhang ^a,b ,
Pengyu Ren ^a ,
Yumeng Cai ^a ,
Xueyun Wang ^a ,
Ke Lan ^{a,b,c
,,} ,
Shuwen Wu ^{a
,,}

a. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China;
b. Medical Research Institute, Wuhan University, Wuhan, 430072, China;
c. Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430072, China

Corresponding author: Ke Lan, klan@whu.edu.cn
Shuwen Wu, shuwenwu@whu.edu.cn
Received Date: 19 March 2024
Accepted Date: 25 June 2024
Available online: 28 June 2024

Abstract

Hand, foot and mouth disease (HFMD), mainly caused by enterovirus 71 (EV71), has frequently occurred in the Asia-Pacific region, posing a significant threat to the health of infants and young children. Therefore, research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming important. The 3D polymerase, as the most critical RNA-dependent RNA polymerase (RdRp) for EV71 replication, is widely targeted to inhibit EV71 infection. In this study, we identified a novel host protein, AIMP2, capable of binding to 3D polymerase and inhibiting EV71 infection. Subsequent investigations revealed that AIMP2 recruits the E3 ligase SMURF2, which mediates the polyubiquitination and degradation of 3D polymerase. Furthermore, the antiviral effect of AIMP2 extended to the CVA16 and CVB1 serotypes. Our research has uncovered the dynamic regulatory function of AIMP2 during EV71 infection, revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies.
- AIMP2
- , Enterovirus 71 (EV71)
- , 3D polymerase
- , E3 ligase SMURF2
- , Ubiquitination

Electronic Supplementary Material

10.1016j.virs.2024.06.009-ESM.docx
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