Complement-related proteins control the flavivirus infection of Aedes aegypti by inducing antimicrobial peptides.
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.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China.
Xiaoping
X
Xiao
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China.
Yang
Y
Liu
School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Xiaoyan
X
Zhang
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China.
Jing
J
Wang
School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Zuofeng
Z
Li
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China.
Xiaojing
X
Pang
Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Penghua
P
Wang
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People's Republic of China.
Gong
G
Cheng
D000330:Aedes / Q000276:immunology* / Q000821:virology; D000818:Animals; D003165:Complement System Proteins / Q000276:immunology*; D005416:Flavivirus / Q000276:immunology*; D018177:Flavivirus Infections / Q000276:immunology*; D019476:Insect Proteins / Q000276:immunology*
D019476:Insect Proteins; D003165:Complement System Proteins