Journal
FRONTIERS IN MICROBIOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2019.00050
Keywords
SARS-CoV; viroporin; inflammasome; IL-1 beta; inflammation
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Funding
- Japan Society for the Promotion of Science [25713018, 15H01254]
- Japanese Ministry of Health, Labour, and Welfare [H25-Shinkou-Ippan-018]
- Takeda Science Foundation
- Uehara Memorial Foundation
- SENSHIN Medical Research Foundation
- Ministry of Science and Technology of the Republic of China [MOST 103-2917-I-564-028]
- Postdoctoral Research Abroad Program
- Grants-in-Aid for Scientific Research [15H01254, 25713018] Funding Source: KAKEN
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Nod-like receptor family, pyrin domain-containing 3 (NLRP3) regulates the secretion of proinflammatory cytokines interleukin 1 beta (IL-1 beta) and IL-18. We previously showed that influenza virus M2 or encephalomyocarditis virus (EMCV) 2B proteins stimulate IL-1 beta secretion following activation of the NLRP3 inflammasome. However, the mechanism by which severe acute respiratory syndrome coronavirus (SARS-CoV) activates the NLRP3 inflammasome remains unknown. Here, we provide direct evidence that SARS-CoV 3a protein activates the NLRP3 inflammasome in lipopolysaccharide-primed macrophages. SARS-CoV 3a was sufficient to cause the NLRP3 inflammasome activation. The ion channel activity of the 3a protein was essential for 3a-mediated IL-1 beta secretion. While cells uninfected or infected with a lentivirus expressing a 3a protein defective in ion channel activity expressed NLRP3 uniformly throughout the cytoplasm, NLRP3 was redistributed to the perinuclear space in cells infected with a lentivirus expressing the 3a protein. K+ efflux and mitochondrial reactive oxygen species were important for SARS-CoV 3a-induced NLRP3 inflammasome activation. These results highlight the importance of viroporins, transmembrane pore-forming viral proteins, in virus-induced NLRP3 inflammasome activation.
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