Nod-like receptor family, pyrin domain-containing 3 (NLRP3) regulates the secretion of proinflammatory cytokines interleukin 1 beta (IL-1β) and IL-18. We previously showed that influenza virus M2 or encephalomyocarditis virus (EMCV) 2B proteins stimulate IL-1β 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-1β 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.
(Netistä löytyy kauni kuva jostain RNA viruksesta, ja NLRP3 inflammasomista: SARS CoV siis osoitti vielä jonkinlaista kirjan kuvalle uskollisita lojaalisuutta ja herättää NLRP3 inflammasia, tosin se ei anna MAVS-tien signaloida, joten interferonivaste on ontuva ajallisesti myöhäinen, mistä tulee isäntäsolulle haittoja siitäkin).
https://media.springernature.com/full/springer-static/image/art%3A10.1038%2Fs41577-019-0165-0/MediaObjects/41577_2019_165_Fig1_HTML.png
Uusi nCoV 2019 on muokannut orf3 erilaiseksi kuin mitä SARSCoV esitti.
"A novel short putative protein with 4 helices and no homology to existing SARS-CoV or SARS-r-CoV protein was found within Orf3b (Figure 4).
Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan
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