2. Academic Validation
  3. AIMP2 restricts EV71 replication by recruiting SMURF2 to promote the degradation of 3D polymerase

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

  • Virol Sin. 2024 Jun 28:S1995-820X(24)00108-1. doi: 10.1016/j.virs.2024.06.009.
Junrui Ren 1,  Lei Yu 2,  Qiuhan Zhang 2,  Pengyu Ren 1,  Yumeng Cai 1,  Xueyun Wang 1,  Ke Lan 3,  Shuwen Wu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
  • 2 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China; Medical Research Institute, Wuhan University, Wuhan, 430072, China.
  • 3 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China; Medical Research Institute, Wuhan University, Wuhan, 430072, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430072, China. Electronic address: klan@whu.edu.cn.
  • 4 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China. Electronic address: shuwenwu@whu.edu.cn.
PMID: 38945214 DOI: 10.1016/j.virs.2024.06.009
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.

Keywords

3D polymerase; AIMP2; E3 ligase SMURF2; Enterovirus 71 (EV71); Ubiquitination.

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