Natural immune system and the induced inflammatory reaction are both important ways for the organism to resist virus infection, but over-activated or continuous inflammatory reaction is a significant cause of virus infection induced organ or tissue damage. Researchers suggested that the virus infection induced inflammasome activation is a major reason of inflammatory reaction in the organism, but the underlying mechanism of virus-induced inflammasome activation was unclear.

Prof. ZHOU Rongbin and Prof. TIAN Zhigang's research groups from University of Science and Technology of China of Chinese Academy of Sciences, in collaboration with Academician HAN Jiahuai, found a novel way to explain why inflammation will happen when the organism is exposed to RNA virus.

In the study, the investigators pointed out that inhibition of necrosome protein RIP1 or RIP3 complex significantly block the RNA virus induced inflammasome activation, including the influenza virus, but the DNA virus induced inflammasome activation is not affected. Experiments showed that RNA virus induced inflammatory reaction promotes the genesis of RIP1-RIP3 complex in macrophage, subsequently the protein complex induces mitochondria damage through DRP1, and then the inflammasome is activated. The investigators found that RNA virus induced inflammatory reaction was significantly reduced in RIP3 defected mice.

These findings suggested that RIP1-RIP3 protein complex and its downstream signaling pathways played essential roles in RNA virus induced NLRP3 inflammasome activation. This not only uncovers the underlying mechanism of RNA virus induced immune inflammation, but also provides potential therapeutic targets for the treatment of virus-infection related inflammatory diseases.

This study entitled "RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway" was published on Nature Immunity.

Figure: The necrosis/inflammation fate of a cell is determined by the phosphorylation state of two important proteins, MLKL and DRP1, respectively. The major determinant in RNA-virus induced inflammasome activation is RIP1-RIP3-DRP1 signaling pathway. (Image by USTC)