Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, 637100, China.
School of Pharmacy, North Sichuan Medical College, Nanchong, 637100, China.
Virol J. 2024 Jun 5;21(1):128. doi: 10.1186/s12985-024-02398-8.
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.
日本脑炎病毒（JEV）的包膜（E）蛋白是病毒感染和吸附宿主细胞的关键蛋白，决定了病毒的毒力，并调节炎症反应的强度。E 蛋白中多个 aa 残基的突变在 JEV 的减毒株中起着关键作用。本研究表明，E389 位点的 Asp 突变为 Gly、Ser 和 His，分别使病毒在细胞中的复制能力显著降低，病毒的神经侵袭性也不同程度减弱。其中，E389 位点的突变增强了 E 蛋白的灵活性，有助于降低神经侵袭性。相比之下，E 蛋白的灵活性降低增强了该株的神经侵袭性。我们的结果表明，E389aa 突变的减毒机制与 E 蛋白的灵活性增加有关。此外，E 蛋白的灵活性增加增强了病毒对肝素抑制的敏感性，这可能导致进入大脑的病毒载量减少。这些结果表明，E389 残基是影响 JEV 毒力的一个潜在位点，该位点 aa 的 E 蛋白的灵活性在确定神经侵袭性方面起着重要作用。
