Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention

Autor(es): Liu, Yang; Zhang, Fuchun; Liu, Jianying; Xiao, Xiaoping; Zhang, Siyin; Qin, Chengfeng; Xiang, Ye; Wang, Penghua; Cheng, Gong


Resumo: 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.


Palavras-Chave: Human diseases; Viral diseases; Lectins; Pathogens; Disease transmission; Public health; Galactose; Virions; Vectors; Life cycle; Infection; Immunization; Blood; Antibodies; Antisera; Cell membranes; Dengue; Risk factors; Vaccines; Dengue virus; Aedes aegypti; Arthropoda; West Nile virus; Flavivirus


Imprenta: Plos Pathogens, v. 10, n. 2, 2014.


Descritores: Aedes aegypti - Cell ; Aedes aegypti - Proteins ; Aedes aegypti - Viral infections ; Aedes aegypti - Virus ; Aedes aegypti - Transmission ; Aedes aegypti - Vaccine ; Aedes aegypti - Dengue ; Aedes aegypti - Public health


Data de publicação: 2014