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- Publisher Website: 10.1096/fj.201802418R
- Scopus: eid_2-s2.0-85070788848
- PMID: 31034780
- WOS: WOS:000478832900014
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Article: Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC
Title | Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC |
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Authors | |
Keywords | SARS coronavirus |
Issue Date | 2019 |
Publisher | Federation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/ |
Citation | The FASEB Journal, 2019, v. 33 n. 8, p. 8865-8877 How to Cite? |
Abstract | Severe acute respiratory syndrome coronavirus (SARS-CoV) is capable of inducing a storm of proinflammatory cytokines. In this study, we show that the SARS-CoV open reading frame 3a (ORF3a) accessory protein activates the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)–mediated ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). SARS-CoV and its ORF3a protein were found to be potent activators of pro–IL-1β gene transcription and protein maturation, the 2 signals required for activation of the NLRP3 inflammasome. ORF3a induced pro–IL-1β transcription through activation of NF-κB, which was mediated by TRAF3-dependent ubiquitination and processing of p105. ORF3a-induced elevation of IL-1β secretion was independent of its ion channel activity or absent in melanoma 2 but required NLRP3, ASC, and TRAF3. ORF3a interacted with TRAF3 and ASC, colocalized with them in discrete punctate structures in the cytoplasm, and facilitated ASC speck formation. TRAF3-dependent K63-linked ubiquitination of ASC was more pronounced in SARS-CoV–infected cells or when ORF3a was expressed. Taken together, our findings reveal a new mechanism by which SARS-CoV ORF3a protein activates NF-κB and the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of p105 and ASC.—Siu, K.-L., Yuen, K.-S., Castaño-Rodriguez, C., Ye, Z.-W., Yeung, M.-L., Fung, S.-Y., Yuan, S., Chan, C.-P., Yuen, K.-Y., Enjuanes, L., Jin, D.-Y. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC. |
Persistent Identifier | http://hdl.handle.net/10722/274571 |
ISSN | 2023 Impact Factor: 4.4 2023 SCImago Journal Rankings: 1.412 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Siu, KL | - |
dc.contributor.author | Yuen, KS | - |
dc.contributor.author | Castaño-Rodriguez, C | - |
dc.contributor.author | Ye, ZW | - |
dc.contributor.author | Yeung, ML | - |
dc.contributor.author | Fung, SY | - |
dc.contributor.author | Yuan, S | - |
dc.contributor.author | Chan, CP | - |
dc.contributor.author | Yuen, KY | - |
dc.contributor.author | Enjuanes, L | - |
dc.contributor.author | Jin, DY | - |
dc.date.accessioned | 2019-08-18T15:04:24Z | - |
dc.date.available | 2019-08-18T15:04:24Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | The FASEB Journal, 2019, v. 33 n. 8, p. 8865-8877 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | http://hdl.handle.net/10722/274571 | - |
dc.description.abstract | Severe acute respiratory syndrome coronavirus (SARS-CoV) is capable of inducing a storm of proinflammatory cytokines. In this study, we show that the SARS-CoV open reading frame 3a (ORF3a) accessory protein activates the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)–mediated ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). SARS-CoV and its ORF3a protein were found to be potent activators of pro–IL-1β gene transcription and protein maturation, the 2 signals required for activation of the NLRP3 inflammasome. ORF3a induced pro–IL-1β transcription through activation of NF-κB, which was mediated by TRAF3-dependent ubiquitination and processing of p105. ORF3a-induced elevation of IL-1β secretion was independent of its ion channel activity or absent in melanoma 2 but required NLRP3, ASC, and TRAF3. ORF3a interacted with TRAF3 and ASC, colocalized with them in discrete punctate structures in the cytoplasm, and facilitated ASC speck formation. TRAF3-dependent K63-linked ubiquitination of ASC was more pronounced in SARS-CoV–infected cells or when ORF3a was expressed. Taken together, our findings reveal a new mechanism by which SARS-CoV ORF3a protein activates NF-κB and the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of p105 and ASC.—Siu, K.-L., Yuen, K.-S., Castaño-Rodriguez, C., Ye, Z.-W., Yeung, M.-L., Fung, S.-Y., Yuan, S., Chan, C.-P., Yuen, K.-Y., Enjuanes, L., Jin, D.-Y. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC. | - |
dc.language | eng | - |
dc.publisher | Federation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/ | - |
dc.relation.ispartof | The FASEB Journal | - |
dc.subject | SARS coronavirus | - |
dc.title | Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC | - |
dc.type | Article | - |
dc.identifier.email | Yeung, ML: pmlyeung@hku.hk | - |
dc.identifier.email | Yuan, S: yuansf@hku.hk | - |
dc.identifier.email | Yuen, KY: kyyuen@hkucc.hku.hk | - |
dc.identifier.email | Jin, DY: dyjin@hku.hk | - |
dc.identifier.authority | Yeung, ML=rp01402 | - |
dc.identifier.authority | Yuen, KY=rp00366 | - |
dc.identifier.authority | Jin, DY=rp00452 | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1096/fj.201802418R | - |
dc.identifier.pmid | 31034780 | - |
dc.identifier.pmcid | PMC6662968 | - |
dc.identifier.scopus | eid_2-s2.0-85070788848 | - |
dc.identifier.hkuros | 301130 | - |
dc.identifier.hkuros | 301655 | - |
dc.identifier.volume | 33 | - |
dc.identifier.issue | 8 | - |
dc.identifier.spage | 8865 | - |
dc.identifier.epage | 8877 | - |
dc.identifier.isi | WOS:000478832900014 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0892-6638 | - |