The molecular basis of the yellow fever virus-specific antibody neutralizing virus revealed by Tianjin Labor and Welfare Institute January 16, 2019 Source: Tianjin Institute of Industrial Biotechnology Yellow fever is an acute infectious disease caused by yellow fever virus that is mainly transmitted by mosquito bites. Yellow fever has a high mortality rate and is highly contagious, and has been included in one of the quarantine infectious diseases prescribed by the World Health Organization. Yellow fever can be prevented by inoculation of a yellow fever vaccine (YF-17D attenuated vaccine). However, factors such as vaccine shortages and widespread immunization have led to the emergence and prevalence of yellow fever. Yellow fever has been prevalent in tropical regions of Africa, Central America and South America in recent years. In 2016, there have been reports of imported yellow fever cases in China. At present, there is no specific treatment for yellow fever, mainly symptomatic treatment and supportive treatment. In recent years, monoclonal antibodies have shown great advantages and potential applications as candidates for the treatment of viral infectious diseases. The envelope protein of the yellow fever virus (E protein) mediates viral invasion into host cells and is a major protective antigen and neutralizing antibody target. The neutralizing antibody against the yellow fever virus can inhibit the invasion of the virus by inhibiting the adhesion of the virus to the host cell or the fusion of the viral envelope membrane with the cell membrane. Recently, the Protein Engineering and Vaccine Research Team of the Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, led by Gao Fu, a member of the Chinese Academy of Sciences, has made new progress in the study of the structure and therapeutic antibodies of the yellow fever virus E protein. They pioneered the resolution of the crystal structure of the high-resolution yellow-hot virus vaccine strain YF-17D before and after fusion of the envelope E protein. The study found that the pre-fusion E protein of the yellow fever virus showed a dimeric conformation, which was similar to the structure of the E protein of other members of the Flavivirus genus. Under low pH conditions, the E protein of the yellow fever virus is in the conformation of the trimeric conformation, and the conformation of the E protein after fusion with the dengue virus and the tick-borne encephalitis virus is similar. During the fusion process, the domain of the E protein was reversed and the secondary structure was rearranged. In addition, they conducted in-depth studies on the function, structure and neutralization mechanism of the yellow fever virus-specific neutralizing antibody 5A. The study found that 5A has a very high potency of neutralizing yellow fever virus (IC50 to ng/mL level) and protects mice against lethal doses of yellow fever virus. Through structural analysis, they found that 5A can combine both the E protein dimer before fusion and the E protein trimer after fusion, like a "double lock". Further functional experiments have also confirmed that 5A can act at multiple stages of viral invasion: blocking the adsorption of the virus on host cells, inhibiting the E protein allosteric and fusion peptide insertion necessary for membrane fusion. This result confirms the "double-lock" mechanism of action of the 5A super-neutralizing virus. The results of this study provide a theoretical basis for the design of the yellow fever virus immunogen/inhibitor and have important guiding significance. The research was funded by the Chinese Academy of Sciences Pilot Project, the National Natural Science Foundation, the Tianjin Natural Science Foundation, the Tianjin Science and Technology Plan Project, the National Key R&D Program, and the National Science and Technology Major Project. The results of the study were published online in the international academic journal Cell Reports. Lu Xishan, assistant researcher of Tianjin Institute of Labor and Technology, is the first author of the paper, and Gao Fu is the author of the communication. Study on the "double-lock" type protection mechanism of yellow-hot virus-specific human neutralizing antibody 5A X Ray Lead Suspender Skirt,0.35 Xray Lead Skirt,0.5 X-Ray Lead Suspender Apron,Radiation Proof Lead Skirt Longkou Kangxie Medical Instrument Co., Ltd , https://www.sdkangxiemedical.com