Novel molecular mechanism of influenza virus-induced inflammatory responses Clues for developing new vaccines and anti-inflammatory drugs
Associate Professor Takeshi Ichinohe at the Institute of Medical Science, the University of Tokyo, and his collaborators in Kyushu University have demonstrated that a mitochondrial outer membrane protein mitofusin 2 is required for influenza virus-induced NLRP3 inflammasome activation.
© Takeshi Ichinohe, Influenza virus infection activates the NLRP3 and stimulates association between mitofusin 2 (Mfn2) and NLRP3. This leads to recruitment of adaptor protein ASC and immature form of caspase-1 (pro-caspase-1) to form the NLRP3 inflammasome. Then, active caspase-1 cleaves the precursor form of IL-1β and IL-18 and stimulates their secretion. OM, outer membrane; IM, inner membrane.
When a small piece of matter enters the nose nothing happens, but when an influenza virus infects the cells of the nasal membrane we develop a fever. This is because the cells of the nasal membrane can detect the presence of the virus. This means that the cells of our body are able to differentiate between a virus and a piece of matter too small to be seen by the eye. Ichinohe and his colleagues have previously demonstrated that influenza the M2 protein activates the NLRP3 inflammasome and the inflammasomes-dependent IL-1β secretion in the lung of mice, which is required for influenza virus-specific adaptive immune responses. However, the precise mechanism by which the NLRP3 is activated in virus-infected cells is not well understood. Now, they have shown that the mitochondrial membrane potential-dependent association between NLRP3 and a mitochondrial outer membrane protein mitofusin 2, a mediator of mitochondrial fusion, is required for influenza virus-induced IL-1β secretion. These results highlight the importance of mitochondria as a platform of influenza virus-induced inflammatory responses.
These results provide clues for developing new vaccines and anti-inflammatory drugs. This study has been published in Proceedings of the National Academy of Sciences of the United States of America (online on October 14 EST)
Press release [pdf] (Japanese)
Paper
Takeshi Ichinohe, Tatsuya Yamazaki, Takumi Koshiba, Yusuke Yanagi,
“Mitochondrial protein mitofusin 2 is required for NLRP3 inflammasome activation after RNA virus infection”,
Proceedings of the National Academy of Sciences
Online Edition: 2013/10/14 (Japan time), doi: 10.1073/pnas.1312571110.
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