The Japanese encephalitis virus NS1' protein facilitates virus infection in mosquitoes.

<h4>Background</h4>The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is known for its capacity to cause severe neurological disease in Asia. Neurotropic flaviviruses within the Japanese encephalitis (JE) serogroup possess the distinctive feature of expressing a unique n...

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Main Authors: Yuwei Liu, Yutian Huang, Ruidong Li, Chang Miao, Yi He, Changhao Xu, Xi Zhu, Bowen Li, Rui Wu, Qin Zhao, Yiping Wen, Xiaobo Huang, Qi-Gui Yan, Yi-Fei Lang, Shan Zhao, Yiping Wang, Yajie Hu, San-Jie Cao, Senyan Du
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://doi.org/10.1371/journal.pntd.0012823
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Summary:<h4>Background</h4>The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is known for its capacity to cause severe neurological disease in Asia. Neurotropic flaviviruses within the Japanese encephalitis (JE) serogroup possess the distinctive feature of expressing a unique nonstructural protein, NS1'. The NS1' protein consists of the full NS1 protein with an additional 52 amino acid extension at the C-terminus and has been demonstrated to exhibit virulence in mammalian hosts upon infection. However, the precise role of the NS1' protein in the mosquito vectors has yet to be elucidated.<h4>Methodology/principal findings</h4>In this study, an NS1'-defective virus (rG66A) was engineered, and its effect on the infection of mosquito cells was investigated. The results demonstrated a significant reduction in the infectivity of the rG66A virus in mosquito cells by RT-qPCR, indicating that the absence of the NS1' protein impedes JEV replication in Culex mosquitoes. Additionally, this research elucidated the underlying mechanism by which the NS1' protein enhances viral infection in mosquitoes by RNA-Seq analysis. Specifically, the NS1' protein was found to facilitate infection through the suppression of antimicrobial peptides (AMPs) regulated by the Toll pathway.<h4>Conclusions/significance</h4>Our research demonstrated that the JEV NS1' protein contributes to immune escape, thereby enhancing viral infection in mosquitoes. This finding offers new insights into the transmission mechanisms of JEV, elucidating novel aspects of viral propagation.
ISSN:1935-2727
1935-2735