Ubiquitin-specific protease 21 aggravates enterovirus 71 (EV71) infection by restricting Lys48-linked ubiquitination of EV71-2A protease
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Updated: May 17, 2025

Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods
Published on: December 21, 2019
Xinyu Yang1, Mengyuan Tang2, Lichao Zang3
1Department of Clinical Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, China; Department of Sperm Bank, Changhai Hospital, Naval Medical University (Second Military Medical University), 200433 Shanghai, China.
Abstract:
EV71-encoded 2A protease (2Apro) plays an important regulatory role in EV71 infection and replication. EV71-2Apro can help the viral immune escape by inhibiting host proteins, thereby disrupting the host antiviral immune response. However, the mechanism by which 2Apro proteins are regulated in host cells remains largely unknown. In this study, we identified USP21 that promotes EV71 infection. We discovered that USP21 downregulated K48-linked polyubiquitination of EV71-2Apro and stabilized 2Apro, ultimately promoting EV71 infection. Furthermore, the small-molecule inhibitor, BAY-805, reduced 2Apro levels and inhibited EV71 infection both in vivo and in vitro. Importantly, we found that the expression level of USP21 was positively correlated with the severity of EV71 infection. This study reveals the crucial regulatory role of USP21 in EV71 infection and provides a potential target for the treatment of EV71 infection.
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