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pubmed:abstractText |
Coxsackievirus B3 (CVB3) is a small RNA virus associated with diseases such as myocarditis, meningitis, and pancreatitis. We have previously demonstrated that proteasome inhibition reduces CVB3 replication and attenuates virus-induced myocarditis. However, the underlying mechanisms by which the ubiquitin/proteasome system regulates CVB replication remain unclear. In this study, we investigated the role of REG?, a member of the 11S proteasome activator, in CVB3 replication. We showed that overexpression of REG? promoted CVB3 replication but that knockdown of REG? led to reduced CVB3 replication. We further demonstrated that REG?-mediated p53 proteolysis contributes, as least in part, to the proviral function of REG?. Although total protein levels of REG? remained unaltered after CVB3 infection, virus infection induced a redistribution of REG? from the nucleus to the cytoplasm, rendering an opportunity for a direct interaction of REG? with viral proteins and/or host proteins (e.g., p53), which controls viral growth and thereby enhances viral infectivity. Further analyses suggested a potential modification of REG? by SUMO following CVB3 infection, which was verified by both in vitro and in vivo sumoylation assays. Sumoylation of REG? may play a role in its nuclear export during CVB3 infection. Taken together, our results present the first evidence that the host REG? pathway is utilized and modified during CVB3 infection to promote efficient viral replication.
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pubmed:affiliation |
James Hogg Research Center, Providence Heart and Lung Institute, University of British Columbia, St. Paul's Hospital, 1081 Burrard St., Vancouver, BC, Canada V6Z 1Y6.
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