Open AccessSPSB2 inhibits hepatitis C virus replication by targeting NS5A for ubiquitination and degradation
Author(s) -
Mingzhen Wang,
Yu Wang,
Yuehong Liu,
Hailong Wang,
Xiu Xin,
Jiadai Li,
Yanling Hao,
Lingling Han,
Fuxun Yu,
Chengchao Zheng,
Chao Shen
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0219989
Subject(s) - ns5a , ubiquitin ligase , ubiquitin , biology , host factor , viral replication , gene knockdown , ddb1 , hepatitis c virus , protein degradation , virology , downregulation and upregulation , viral protein , signal transducing adaptor protein , viral structural protein , microbiology and biotechnology , virus , hepacivirus , cell culture , viral entry , signal transduction , genetics , gene
Hepatitis C virus (HCV) replication involves many viral and host factors. Host factor SPRY domain- and SOCS box-containing protein 2(SPSB2) belongs to SPSB family, and it recruits target proteins by the SPRY domain and forms E3 ubiquitin ligase complexes by the SOCS box. As an adaptor protein, it can regulate the host’s response to infection, but little is known about whether SPSB2 plays a role in HCV replication. In the present study, we found that HCV infection significantly upregulated the mRNA and protein levels of SPSB2 in HCVcc-infected cells. Exogenous expression of SPSB2 in hepatoma cells decreased HCV RNA and protein levels which depended on the SOCS box, while knockdown of endogenous SPSB2 increased HCV RNA and protein levels. Additionally, we demonstrated that SPSB2 interacted with HCV structural protein E1 and nonstructural protein protein 5A (NS5A) via the C-terminal portion of the SPSB2 SPRY domain. Furthermore, SPSB2 induced NS5A ubiquitination and mediated NS5A degradation. Collectively, this study discovered host factor SPSB2 significantly inhibits HCV replication by interacting and degrading NS5A.