The mutation of Japanese encephalitis virus envelope protein residue 389 attenuates viral neuroinvasiveness

Autor: Rong Huang, Yajing He, Chenghua Zhang, Yue Luo, Chen Chen, Ning Tan, Yang Ren, Kui Xu, Lei Yuan, Jian Yang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Virology Journal, Vol 21, Iss 1, Pp 1-12 (2024)
Druh dokumentu: article
ISSN: 1743-422X
DOI: 10.1186/s12985-024-02398-8
Popis: Abstract The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje