Prof. Zhou Rongbin and Prof. Tian Zhigang's research groups from the School of Life Science, in collaboration with Academician Han Jiahuai, found  a novel way to explain why inflammation will happen when the organism is exposed to RNA virus.

Natural immune system and the induced inflammatory reaction are both important ways for the organism to resist virus infection, but on the other hand, over-activated or continuous inflammatory reaction is a significant cause of virus infection induced organ or tissue damage. Recently researches 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.

In their work, the investigators pointed out that inhibition of necrosome protein RIP1 or RIP3 complex can significantly block the RNA virus induced inflammasome activation, including the influenza virus, but the DNA virus induced inflammasome activation will not be affected. Further experiments showed that RNA virus induced inflammatory reaction can promote the genesis of RIP1-RIP3 complex in macrophage, subsequently the protein complex will induce mitochondria damage through DRP1, and then the inflammasome was activated. Finally, 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.

Prof. Zhou Rongbin’s research group work on innate immune recognition, regulation and mechanism of diseases for a long time, and have already acquired a number of important research results. Since the year of 2013, they’ve already published research papers on world class immunology research journals like Nature Immunology, Immunity, J Exp Med, etc.

This research achievement entitled "RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway" was published on Oct. 19th in Nature Immunity.

Fig: 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.

(HUANG JUN ,USTC News Center)