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Ubiquitination Is Required for Effective Replication of Coxsackievirus B3
Author(s) -
Si Xiaoning,
Gao Guang,
Zhang Jingchun,
Wang Jerry,
Wang Yahong,
McManus Bruce M.,
Luo Honglin
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a644-b
Subject(s) - ubiquitin , proteasome , viral replication , small interfering rna , gene knockdown , biology , microbiology and biotechnology , protein degradation , deubiquitinating enzyme , viral protein , rna , virology , virus , biochemistry , gene
The importance of the ubiquitin/proteasome pathway (UPP) in viral pathogenesis has become increasingly apparent. We have previously demonstrated that the UPP plays a key role in the replication of coxsackievirus B3 (CVB3), an important human pathogen. We have shown that CVB3 replication is markedly reduced by proteasome inhibitors. To further elucidate the underlying mechanisms by which the UPP regulates CVB3 replication, we examined the delicate interplay between the UPP and CVB3 and focused on the role of ubiquitination in viral lifecycle. We found that proteasome inhibition decreased CVB3 RNA replication, protein synthesis, and viral titers. There were no apparent changes in proteasome activities following CVB3 infection. Interestingly, viral infection led to an accumulation of protein‐ubiquitin conjugates, accompanied by a decreased protein expression of free ubiquitin. These data suggested that protein ubiquitination was activated after infection, implicating an important role of ubiquitination in the UPP‐mediated viral replication and/or protein degradation. Using siRNA, we demonstrated that knockdown of ubiquitin significantly reduced viral protein synthesis, possibly through down‐regulation of protein ubiquitination and subsequent degradation. Finally, we investigated the potential mechanisms of increased ubiquitination by examining several enzymes involved in the process of ubiquitination and deubiquitination. However, no significant changes were observed. Taken together, we conclude that CVB3 infection promotes protein ubiquitination, contributing to effective viral replication. This work is supported by CIHR‐HSFC IMPACT Strategic Training Fellowship and CIHR Michael Smith Fellowship.