On 18th July, CAS member Prof. Shu Hongbing and his research group published their research achievements on the leading journal Nature Immunology. The paper entitled iRhom2 is essential for innate immunity to DNA viruses by mediating trafficking and stability of the adaptor STING demonstrates the latest research findings in this field.
This research is conducted by doctoral candidate Luo Weiwei and Dr. Li Shu under Shu Hongbing’s guidance. Shu is also the corresponding author of this paper. It is funded by Major National Science Research Program and NSFC (Natural Science Foundation of China).
It is known that innate immunity is the first line of defense against virus infection and it plays an essential role in the early stage of the host’s antiviral immunity. In 2008, Shu Hongbing’s research group, cooperated with the research group led by Glen Barber from University of Miami (USA), discovered adaptor protein STING/MITA, which is essential for the innate immunity to DNA viruses. The new finding drew wide attention and almost immediately became a hotspot in immunology study. The relevant papers also became the key documents in this field.
In the new research, Shu Hongbing and his group find that iRhom2 is essential for innate immunity to DNA viruses. Their tests on the knockout mice prove that iRhom2 is indispensable to provide the host with protection from DNA virus infection. Also,biochemistry and cytobiology experiments indicates that iRhom2 regulates STING through two mutually exclusive pathways. For one thing, iRhom2 bridges the transporting-associated protein TRAPb with STING, transferring it from endoplasmic reticulum to the peripheral micro-body. The transcription factor IRF3 in the downstream gets activated in the same process. For another thing, iRhom2 recruits deubiquitinating enzymes EIF3S5 and maintains the stable protein level of STING by removing ubiquitination connected by K48. This helps to activate the transcription factor IRF3 in the downstream.
This research for the first time demonstrates the significance of iRhom2 in the innate immunity to DNA viruses and provides new clues to know more about its physiological function. More crucially, it illustrates the essential regulatory mechanism of organ against DNA virus immunity reaction, which provides the potential molecular targets to prevent the diseases caused by DNA virus infection and autoimmune diseases.
Shu Hongbing and his research group
（Picture：the Institute of Medicine）
(Rewritten by Shen Yuxi, edited by Hu Sijia)
