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Research


 We try to understand the mechanism by which viral infection at the mucosal surface is recognized and how the recognition process is involved in the generation of adaptive immunity. We have previously demonstrated that unlike toll-like receptors and retinoic acid-inducible gene I (RIG-I)-like helicases that recognize viral RNA, the NLR family, pyrin domain containing 3 (NLRP3) senses disturbance of intracellular ionic concentration induced by the expression of virus-encoded ion channels (viroporins) such as the influenza A virus M2 protein and the encephalomyocarditis virus (EMCV) 2B protein. Recently, we demonstrated that the nonstructural protein 1 (NS1) of influenza A virus interacts with the NLRP3 to inhibit a NLRP3/ASC-induced single speck formation required for full activation of inflammasomes and IL-1beta secretion. These results provide a basis for understanding the viral pathogenesis and developing effective vaccines against viral pathogens.


1) Activation of the NLRP3 inflammasome by viroporins


Moriyama M, Chen IY, Kawaguchi A, Koshiba T, Nagata K, Takeyama H, Hasegawa H, Ichinohe T. The RNA- and TRIM25-binding domains of influenza virus NS1 protein are essential for suppression of NLRP3 inflammasome-mediated IL-1β secretion. J Virol. 2016 Mar 28;90(8):4105-14.



Ichinohe T, Yamazaki T, Koshiba T, Yanagi Y. Mitochondrial protein mitofusin 2 is required for NLRP3 inflammasome activation after RNA virus infection. Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17963-8.



UTokyo Research