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The Japanese encephalitis virus NS1' protein facilitates virus infection in mosquitoes
Yuwei Liu1, Yutian Huang1, Ruidong Li1
1Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Background:
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.
Methodology/Principal Findings:
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.
Conclusions/Significance:
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.
Insights
Japanese encephalitis virus (JEV) NS1' protein aids mosquito infection by suppressing immune responses. This study reveals how NS1' protein enhances JEV replication in mosquitoes, offering new insights into viral transmission.
Area of Science:
- Virology
- Vector Biology
- Immunology
Background:
- Japanese encephalitis virus (JEV) causes severe neurological disease.
- JEV belongs to the flavivirus family and is transmitted by mosquitoes.
- A unique NS1' protein is expressed by neurotropic flaviviruses in the JE serogroup.
Purpose of the Study:
- To investigate the role of the JEV NS1' protein in mosquito vectors.
- To elucidate the mechanism by which NS1' protein enhances viral infection in mosquitoes.
Main Methods:
- Engineered an NS1'-defective JEV (rG66A) for infection studies.
- Utilized RT-qPCR to assess viral infectivity in mosquito cells.
- Employed RNA-Seq analysis to uncover the underlying molecular mechanisms.
Main Results:
- The absence of NS1' protein significantly reduced JEV infectivity in Culex mosquito cells.
- NS1' protein was found to suppress antimicrobial peptides (AMPs) via the Toll pathway.
- This suppression facilitates enhanced viral infection and replication in mosquitoes.
Conclusions:
- The JEV NS1' protein plays a crucial role in immune evasion within mosquito vectors.
- NS1' protein enhances JEV infection by downregulating the mosquito's innate immune response.
- This study provides novel insights into JEV transmission dynamics and viral propagation mechanisms.
