Mosquito Defensins Enhance Japanese Encephalitis Virus Infection by Facilitating Virus Adsorption and Entry within the Mosquito.

Ke Liu,Denian Miao,Shumin Xi,Jianchao Wei,Huaimin Zhu,Beibei Li,Donghua Shao,Muddassar Hameed,Changguang Xiao,Yafeng Qiu,Abdul Wahaab,Zongjie Li,Zhiyong Ma,Susana López

doi:10.1128/jvi.01164-20

Abstract

Japanese encephalitis virus (JEV) is a viral zoonosis that can cause viral encephalitis, death, and disability. Although the Culex mosquito is the primary vector of JEV, little is known about JEV transmission by this kind of mosquito. Here, we found that mosquito defensin facilitated the adsorption of JEV on target cells via the defensin/lipoprotein receptor-related protein 2 (LRP2) axis. Mosquito defensin bound the ED III domain of the viral envelope (E) protein and directly mediated efficient virus adsorption on the target cell surface; the receptor LRP2, which is expressed on the cell surface, affected defensin-dependent adsorption. As a result, mosquito defensin enhanced JEV infection in the salivary gland, increasing the possibility of viral transmission by mosquitoes. These findings demonstrate the novel role of mosquito defensin in JEV infection and the mechanisms through which the virus exploits mosquito defensin for infection and transmission.IMPORTANCE In this study, we observed the complex roles of mosquito defensin in JEV infection; mosquito defensin exhibited a weak antiviral effect but strongly enhanced binding. In the latter, defensin directly binds the ED III domain of the viral E protein and promotes the adsorption of JEV to target cells by interacting with lipoprotein receptor-related protein 2 (LRP2), thus accelerating virus entry. Together, our results indicate that mosquito defensin plays an important role in facilitating JEV infection and potential transmission.

Highlights

Japanese encephalitis virus (JEV), a member of Flaviviridae flavivirus, is prevalent inAsia-Pacific tropical and subtropical regions [1,2,3]
More than 100,000 people are at risk of JEV infection, and immunocompromised children and older individuals are at particular risk [9, 10]
Our results indicate that the facilitation effect of mosquito defensin plays an important role in JEV infection and potential transmission

Summary

Introduction

Japanese encephalitis virus (JEV), a member of Flaviviridae flavivirus, is prevalent inAsia-Pacific tropical and subtropical regions [1,2,3]. Japanese encephalitis virus (JEV), a member of Flaviviridae flavivirus, is prevalent in. JEV is mainly transmitted through mosquito bites [2, 4]. The World Health Organization has reported that more than 67,900 cases of JEV infection globally each year, more than 10,000 of which are fatal. The clinical incidence of Japanese encephalitis is increasing as well, owing to an increase in the habitat range and activity of mosquitoes carrying JEV as the climate warms [2, 4, 9]. Few studies have addressed the transmission mechanism of JEV by mosquito vectors [4]. A detailed understanding of the interaction between JEV and mosquito vectors will be essential to improve control of JEV transmission

Methods

Results

Conclusion