A Neuron-Specific Antiviral Mechanism Prevents Lethal Flaviviral Infection of Mosquitoes

PLoS Pathogens

Gong Cheng¹  Rudian Zhang¹  Xiaoping Xiao²  Xiaojing Pang²  Penghua Wang²  Guodong Liang³ 

[1] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People's Republic of China;Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China;School of Life Science, Tsinghua University, Beijing, People's Republic of China

关键词: Mosquitoes;    Antibodies;    Drosophila melanogaster;    Cell membranes;    Enzyme-linked immunoassays;    Viral load;    Apoptosis;    Viral entry;   

DOI  :  10.1371/journal.ppat.1004848

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Mosquitoes are natural vectors for many etiologic agents of human viral diseases. Mosquito-borne flaviviruses can persistently infect the mosquito central nervous system without causing dramatic pathology or influencing the mosquito behavior and lifespan. The mechanism by which the mosquito nervous system resists flaviviral infection is still largely unknown. Here we report that an Aedes aegypti homologue of the neural factor Hikaru genki (AaHig) efficiently restricts flavivirus infection of the central nervous system. AaHig was predominantly expressed in the mosquito nervous system and localized to the plasma membrane of neural cells. Functional blockade of AaHig enhanced Dengue virus (DENV) and Japanese encephalitis virus (JEV), but not Sindbis virus (SINV), replication in mosquito heads and consequently caused neural apoptosis and a dramatic reduction in the mosquito lifespan. Consistently, delivery of recombinant AaHig to mosquitoes reduced viral infection. Furthermore, the membrane-localized AaHig directly interfaced with a highly conserved motif in the surface envelope proteins of DENV and JEV, and consequently interrupted endocytic viral entry into mosquito cells. Loss of either plasma membrane targeting or virion-binding ability rendered AaHig nonfunctional. Interestingly, Culex pipien pallens Hig also demonstrated a prominent anti-flavivirus activity, suggesting a functionally conserved function for Hig. Our results demonstrate that an evolutionarily conserved antiviral mechanism prevents lethal flaviviral infection of the central nervous system in mosquitoes, and thus may facilitate flaviviral transmission in nature.

【 授权许可】

CC BY