| Summary: | 博士 === 國立臺灣大學 === 微生物學研究所 === 99 === Influenza A virus RNA replication requires an intricate regulatory network involving viral and cellular proteins. Here we examined the roles of cellular ubiquitinating/deubiquitinating enzymes (DUBs). We found that down-regulation of a cellular deubiquitinating enzyme USP11 resulted in enhanced virus production, suggesting that USP11 could inhibit influenza virus replication. Conversely, over-expression of USP11 inhibited specifically viral genomic RNA replication, and this inhibition required the deubiquitinase activity. Furthermore, we showed that USP11 interacted with PB2, PA and NP of viral RNA replication complex, and that NP is a mono-ubiquitinated protein and can be deubiquitinated by USP11 in vivo. Finally, we identified K184 as the ubiquitination site on NP and this residue is crucial for virus RNA replication. We propose that ubiquitination/deubiquitination of NP can be manipulated for antiviral therapeutic purposes.
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