Complement-Related Proteins Control the Flavivirus Infection of Aedes aegypti by Inducing Antimicrobial Peptides

PLoS Pathogens

Xiaoping Xiao¹  Xiaojing Pang¹  Gong Cheng¹  Jing Wang¹  Yang Liu¹  Zuofeng Li²  Xiaoyan Zhang²  Penghua Wang³ 

[1] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China;School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China;Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, United States of America

关键词: Mosquitoes;    Complement system;    Enzyme-linked immunoassays;    Drosophila melanogaster;    Antibodies;    Virions;    Aedes aegypti;    Dengue virus;   

DOI  :  10.1371/journal.ppat.1004027

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The complement system functions during the early phase of infection and directly mediates pathogen elimination. The recent identification of complement-like factors in arthropods indicates that this system shares common ancestry in vertebrates and invertebrates as an immune defense mechanism. Thioester (TE)-containing proteins (TEPs), which show high similarity to mammalian complement C3, are thought to play a key role in innate immunity in arthropods. Herein, we report that a viral recognition cascade composed of two complement-related proteins limits the flaviviral infection of Aedes aegypti. An A. aegypti macroglobulin complement-related factor (AaMCR), belonging to the insect TEP family, is a crucial effector in opposing the flaviviral infection of A. aegypti. However, AaMCR does not directly interact with DENV, and its antiviral effect requires an A. aegypti homologue of scavenger receptor-C (AaSR-C), which interacts with DENV and AaMCR simultaneously in vitro and in vivo. Furthermore, recognition of DENV by the AaSR-C/AaMCR axis regulates the expression of antimicrobial peptides (AMPs), which exerts potent anti-DENV activity. Our results both demonstrate the existence of a viral recognition pathway that controls the flaviviral infection by inducing AMPs and offer insights into a previously unappreciated antiviral function of the complement-like system in arthropods.

【 授权许可】

CC BY