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Deneddylation by SENP8 restricts hepatitis B virus propagation
Author(s) -
Chen David Virya,
Suzuki Tatsuya,
Itoh Yumi,
Maeda Yusuke,
Hirano Junki,
Haga Saori,
Zhang He,
Ito Daiki,
Matsuura Yoshiharu,
Okamoto Toru
Publication year - 2021
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/1348-0421.12874
Subject(s) - nedd8 , neddylation , ubiquitin , biology , hepatitis b virus , hbcag , glycosylation , isg15 , virology , microbiology and biotechnology , virus , biochemistry , gene , ubiquitin ligase , hbsag
Proteins newly synthesized from messenger RNA undergo Posttranslational modifications (PTMs) such as phosphorylation, glycosylation, methylation, and ubiquitination. These PTMs have important roles in protein stability, localization, and conformation and have been reported to be involved in hepatitis B virus (HBV) propagation. Although ubiquitination plays an essential role in HBV life cycles, the involvement of ubiquitin‐like proteins (UBLs) in HBV life cycles has been understudied. Through comprehensive gain‐ and loss‐of‐function screening of UBLs, we observed that neddylation, a PTM in which neural precursor cell, expressed developmentally downregulated 8 (NEDD8) is conjugated to substrate proteins, was required for efficient HBV propagation. We also found that overexpression of sentrin‐specific protease 8 (SENP8), which cleaves conjugated NEDD8, suppressed HBV propagation. Further, the catalytic activity of SENP8 was required for the suppression of HBV propagation. These results indicated that the reduction of neddylation negatively regulated HBV propagation. In addition, we demonstrated that suppression of HBV propagation via SENP8 overexpression was independent of hepatitis B protein X (HBx) and HBV promoter activity. Therefore, our data suggested that neddylation plays an important role in the late stages of HBV life cycles.