Ubiquitination and deubiquitination of NP protein regulates influenza A virus RNA replication
Influenza A virus RNA replication requires an intricate regulatory network involving viral and cellular proteins. In this study, we examined the roles of cellular ubiquitinating/deubiquitinating enzymes (DUBs). We observed that downregulation of a cellular deubiquitinating enzyme USP11 resulted in e...
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| Veröffentlicht in: | The EMBO journal 2010-11, Vol.29 (22), p.3879-3890 |
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| description | Influenza A virus RNA replication requires an intricate regulatory network involving viral and cellular proteins. In this study, we examined the roles of cellular ubiquitinating/deubiquitinating enzymes (DUBs). We observed that downregulation of a cellular deubiquitinating enzyme USP11 resulted in enhanced virus production, suggesting that USP11 could inhibit influenza virus replication. Conversely, overexpression of USP11 specifically inhibited 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 monoubiquitinated 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.
Monoubiquitination of the NP protein of influenza virus A is critical for efficient viral replication. The deubiquitinating enzyme USP11 removes this modification, inhibiting viral infectivity. |
| doi_str_mv | 10.1038/emboj.2010.250 |
| format | Article |
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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.
Monoubiquitination of the NP protein of influenza virus A is critical for efficient viral replication. The deubiquitinating enzyme USP11 removes this modification, inhibiting viral infectivity.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/emboj.2010.250</identifier><identifier>PMID: 20924359</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Amino Acid Sequence ; Cell Line ; Cellular biology ; EMBO23 ; EMBO31 ; Gene Expression Regulation, Viral ; Genome, Viral ; Humans ; Influenza ; Influenza A virus ; Influenza A virus - genetics ; Influenza A virus - metabolism ; Influenza A virus - physiology ; Influenza, Human - virology ; Molecular biology ; Molecular Sequence Data ; Nucleoproteins - metabolism ; Ribonucleic acid ; RNA ; RNA Replicase - metabolism ; RNA, Viral - genetics ; Thiolester Hydrolases - genetics ; Thiolester Hydrolases - metabolism ; Ubiquitination ; USP11 ; Viral Proteins - genetics ; Viral Proteins - metabolism ; Virus Replication ; Viruses</subject><ispartof>The EMBO journal, 2010-11, Vol.29 (22), p.3879-3890</ispartof><rights>European Molecular Biology Organization 2010</rights><rights>Copyright © 2010 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Nov 17, 2010</rights><rights>Copyright © 2010, European Molecular Biology Organization 2010 European Molecular Biology Organization</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6670-16794aff8e0d4f847cdbf5bc3a83ce4f1c2b98ea343a94f7650a163e8c6bb2353</citedby><cites>FETCH-LOGICAL-c6670-16794aff8e0d4f847cdbf5bc3a83ce4f1c2b98ea343a94f7650a163e8c6bb2353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989104/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989104/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,41120,42189,45574,45575,46409,46833,51576,53791,53793</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/emboj.2010.250$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20924359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liao, Tsai-Ling</creatorcontrib><creatorcontrib>Wu, Chung-Yi</creatorcontrib><creatorcontrib>Su, Wen-Chi</creatorcontrib><creatorcontrib>Jeng, King-Song</creatorcontrib><creatorcontrib>Lai, Michael M C</creatorcontrib><title>Ubiquitination and deubiquitination of NP protein regulates influenza A virus RNA replication</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Influenza A virus RNA replication requires an intricate regulatory network involving viral and cellular proteins. In this study, we examined the roles of cellular ubiquitinating/deubiquitinating enzymes (DUBs). We observed that downregulation of a cellular deubiquitinating enzyme USP11 resulted in enhanced virus production, suggesting that USP11 could inhibit influenza virus replication. Conversely, overexpression of USP11 specifically inhibited 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 monoubiquitinated 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.
Monoubiquitination of the NP protein of influenza virus A is critical for efficient viral replication. The deubiquitinating enzyme USP11 removes this modification, inhibiting viral infectivity.</description><subject>Amino Acid Sequence</subject><subject>Cell Line</subject><subject>Cellular biology</subject><subject>EMBO23</subject><subject>EMBO31</subject><subject>Gene Expression Regulation, Viral</subject><subject>Genome, Viral</subject><subject>Humans</subject><subject>Influenza</subject><subject>Influenza A virus</subject><subject>Influenza A virus - genetics</subject><subject>Influenza A virus - metabolism</subject><subject>Influenza A virus - physiology</subject><subject>Influenza, Human - virology</subject><subject>Molecular biology</subject><subject>Molecular Sequence Data</subject><subject>Nucleoproteins - metabolism</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Replicase - metabolism</subject><subject>RNA, Viral - genetics</subject><subject>Thiolester Hydrolases - genetics</subject><subject>Thiolester Hydrolases - metabolism</subject><subject>Ubiquitination</subject><subject>USP11</subject><subject>Viral Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Liao, Tsai-Ling</au><au>Wu, Chung-Yi</au><au>Su, Wen-Chi</au><au>Jeng, King-Song</au><au>Lai, Michael M C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ubiquitination and deubiquitination of NP protein regulates influenza A virus RNA replication</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2010-11-17</date><risdate>2010</risdate><volume>29</volume><issue>22</issue><spage>3879</spage><epage>3890</epage><pages>3879-3890</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>Influenza A virus RNA replication requires an intricate regulatory network involving viral and cellular proteins. In this study, we examined the roles of cellular ubiquitinating/deubiquitinating enzymes (DUBs). We observed that downregulation of a cellular deubiquitinating enzyme USP11 resulted in enhanced virus production, suggesting that USP11 could inhibit influenza virus replication. Conversely, overexpression of USP11 specifically inhibited 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 monoubiquitinated 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.
Monoubiquitination of the NP protein of influenza virus A is critical for efficient viral replication. The deubiquitinating enzyme USP11 removes this modification, inhibiting viral infectivity.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>20924359</pmid><doi>10.1038/emboj.2010.250</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence Cell Line Cellular biology EMBO23 EMBO31 Gene Expression Regulation, Viral Genome, Viral Humans Influenza Influenza A virus Influenza A virus - genetics Influenza A virus - metabolism Influenza A virus - physiology Influenza, Human - virology Molecular biology Molecular Sequence Data Nucleoproteins - metabolism Ribonucleic acid RNA RNA Replicase - metabolism RNA, Viral - genetics Thiolester Hydrolases - genetics Thiolester Hydrolases - metabolism Ubiquitination USP11 Viral Proteins - genetics Viral Proteins - metabolism Virus Replication Viruses |
| title | Ubiquitination and deubiquitination of NP protein regulates influenza A virus RNA replication |
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