Release date: 2018-01-31

This work reported the cryo-electron microscopic structure of the JEV encephalitis virus and the two therapeutic antibodies 2F2 and 2H4 complexes, and elucidated the function and mechanism of the two neutralizing antibodies. This is another important research result of Raozi and the team following the analysis of the full-particle three-dimensional fine structure of Japanese encephalitis virus (JEV).

Patients with encephalitis have a higher mortality rate, and survivors are prone to neurological sequelae. Therefore, the development of specific drugs and new vaccines against Japanese encephalitis virus is of great significance for the prevention and treatment of this epidemic. The 2F2 and 2H4 neutralizing antibodies were high- and high-activity antibodies screened by the Department of Microbiology of the Fourth Military Medical University 30 years ago. They were used for clinical treatment of patients during the special period of frequent outbreaks of Japanese encephalitis. Shows good safety and therapeutic effects.

In the study, the researchers first discovered that the 2F2 and 2H4 neutralizing antibodies interact only with Japanese encephalitis virus and do not interact with the dengue virus, Zika virus and yellow fever virus, which are both Flaviviruses, and Both antibodies showed high affinity. Both of these antibodies have excellent neutralizing activity by neutralization experiments at the cellular level. Animal-level protection experiments found that the two antibodies completely cleared the Japanese encephalitis virus in the brain of infected mice and completely cured the infected mice.

The researchers analyzed the composite structure of 4.7 Ã… JEV-2F2 and 4.6 Ã… JEV-2H4 by cryo-electron microscopy. Through structural analysis, it was found that antibodies with higher neutralizing activity in the flavivirus genus bind to the quaternary structure of the E protein, and these antibodies are virus-specific neutralizing antibodies. Therefore, according to the above characteristics, a new vaccine specific for viruses can be designed. By further studying the mechanism of action of the two neutralizing antibodies, the researchers found that these two antibodies not only prevented the binding of the virus and cells, but also prevented the fusion of the virus and cells under acidic conditions, and played a leading role.

The research was supported by the National Natural Science Foundation of China, the 973 Program of the Ministry of Science and Technology, and the pilot project of the Chinese Academy of Sciences. It was also supported by Qin Chengfeng, a researcher at the Military Medical Research Institute, and Liu Shanyi, a researcher at the Ohio State University. Wang Xiangxi, a researcher at the Institute of Biophysics, Chinese Academy of Sciences, Xu Zhikai, a professor at the Air Force Military Medical University, and Rao Zihe, an academician of the Chinese Academy of Sciences, are co-authors of this article. Rao Zi and team doctoral students Qiu Xiaodi and Associate Professor of the Air Force Military Medical University Lei Yingfeng are the first in this paper. Author.

Source: Science Network

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