Transmission-Blocking Antibodies against Mosquito C-Type Lectins for Dengue Prevention

PLoS Pathogens

Xiaoping Xiao¹  Jianying Liu¹  Siyin Zhang¹  Gong Cheng¹  Ye Xiang¹  Yang Liu¹  Fuchun Zhang²  Penghua Wang³  Chengfeng Qin⁴ 

[1] Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China;Guangzhou 8th People's Hospital, Guangzhou, People's Republic of China;Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, United States of America;State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China

关键词: Mosquitoes;    Immune serum;    Dengue virus;    Lectins;    Blood;    Arboviral infections;    Vector-borne diseases;    West Nile virus;   

DOI  :  10.1371/journal.ppat.1003931

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

C-type lectins are a family of proteins with carbohydrate-binding activity. Several C-type lectins in mammals or arthropods are employed as receptors or attachment factors to facilitate flavivirus invasion. We previously identified a C-type lectin in Aedes aegypti, designated as mosquito galactose specific C-type lectin-1 (mosGCTL-1), facilitating the attachment of West Nile virus (WNV) on the cell membrane. Here, we first identified that 9 A. aegypti mosGCTL genes were key susceptibility factors facilitating DENV-2 infection, of which mosGCTL-3 exhibited the most significant effect. We found that mosGCTL-3 was induced in mosquito tissues with DENV-2 infection, and that the protein interacted with DENV-2 surface envelop (E) protein and virions in vitro and in vivo. In addition, the other identified mosGCTLs interacted with the DENV-2 E protein, indicating that DENV may employ multiple mosGCTLs as ligands to promote the infection of vectors. The vectorial susceptibility factors that facilitate pathogen invasion may potentially be explored as a target to disrupt the acquisition of microbes from the vertebrate host. Indeed, membrane blood feeding of antisera against mosGCTLs dramatically reduced mosquito infective ratio. Hence, the immunization against mosGCTLs is a feasible approach for preventing dengue infection. Our study provides a future avenue for developing a transmission-blocking vaccine that interrupts the life cycle of dengue virus and reduces disease burden.

【 授权许可】

CC BY