title: Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention.
abstract: 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.
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangzhou 8th People's Hospital, Guangzhou, People's Republic of China.
authors.forename: Fuchun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Siyin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Penghua
authors.initials: P
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Gong
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology*; D009033:Culicidae; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D006790:Host-Parasite Interactions / Q000276:immunology*; D047468:Immunoprecipitation; D007303:Insect Vectors / Q000276:immunology; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019138:Antibodies, Blocking; D037181:Lectins, C-Type