New Knowledge Of human immune guards "combat effectiveness" upgrade "secret"

Virus infecting human body is just like an alien invading our home earth. To deal with these "extremely destructive" invaders, how to strengthen "defense" and "army construction" to protect human homeland has always been an important issue concerned by scientists and the public.if the pathogenic microorganisms can not be controlled timely and effectively, it may cause death or sequelae.in recent years, new virus infections, such as avian influenza virus and Zika virus, need to be prevented and treated with antiviral drugs or vaccines.the research team of Wang Hongyan of the center of excellence and innovation of molecular cell science of Chinese Academy of Sciences (Institute of Biochemistry and cell biology, hereinafter referred to as the center of excellence in molecular and cellular biology) and Wei bin Laboratory of Shanghai University have found that intracellular 7-dehydrocholesterol reductase (DHCR7) can down regulate the function and mechanism of innate immune antiviral infection of the organism, and the activity of this enzyme can be significantly enhanced The "guard" of human immunity -- the "fighting power" of macrophages to remove zikv, H1N1, HSV and other viruses.this study provides a new drug target for resistance to new or highly pathogenic virus infection.the related papers were published online in the international academic journal immunity on December 25, Beijing time, and the related invention has been applied for patent.cholesterol is closely related to cardiovascular disease, but recent studies have shown that reducing cholesterol synthesis in macrophages can also help to resist viral infection.in this study, we screened a reductase "DHCR7" which was "abnormally expressed" in DNA virus and RNA virus infection.DHCR7 can convert 7-dehydrocholesterol (7-DHC) into cholesterol, which is the last step in cholesterol biosynthesis.after blocking the activity of DHCR7 in the experiment, researchers can reduce cholesterol and promote the accumulation of 7-DHC, and finally enhance the production level of interferon type 1 (such as IFN β), so as to effectively prevent virus infection.the researchers further explored the construction of the "signal pathway", and found that it was similar to the "baton transmission process": 7-DHC acts as a radar on the membrane surface of immune guard macrophages, transmitting the "danger signal" of virus invasion to Akt3 in macrophages and promoting the activation of Akt3; Akt3 then combined with IRF3, which is responsible for gene transcription, to tell IRF3 to produce more urgently IFN β.this signaling pathway is like a "assembly signal", which finally makes macrophages clear the invading virus as soon as possible.interestingly, tamoxifen, a chemotherapeutic drug for breast cancer, was approved by the food and Drug Administration of the United States to inhibit DHCR7 activity. In this study, researchers found that tamoxifen has a new function of inhibiting herpes virus and Saika virus infection.this study revealed a new mechanism of cholesterol metabolite 7-DHC to improve antiviral response by influencing the signal transduction pathway of innate immunity. It was also pointed out that targeting DHCR7 can enhance the function of resistance to various viral infections, which will help to develop new anti viral drugs.the center of molecular cell excellence, Dr. Xiao Jun and postdoctoral Li Weiyun are the co first authors of this paper.this research work has obtained the cooperation of Zhai Qiwei, Shanghai Institute of nutrition and health, Chinese Academy of Sciences, Chen Hualan, academician of Harbin Institute of veterinary medicine, Chinese Academy of Agricultural Sciences, and Yang Zhongzhou, Institute of model animals, Nanjing University.the research was supported by NSFC, Ministry of science and technology, Chinese Academy of Sciences, etc., and supported by animal platform, cell platform and molecular biology technology platform of molecular cell center.note: when an "alien invades the earth", the early warning center (7-DHC) on the earth's surface sends an emergency signal (Akt3) to the IRF3, which makes the earth guards (IFN β) assemble rapidly and transport them to the universe to resist the alien bodies.source: Center for excellence in molecular and cellular science, Chinese Academy of Sciences