title: mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes.
abstract: Japanese encephalitis virus (JEV) is an arthropod-borne flavivirus prevalent in Asia and the Western Pacific and is the leading cause of viral encephalitis. JEV is maintained in a transmission cycle between mosquitoes and vertebrate hosts, but the molecular mechanisms by which the mosquito vector participates in transmission are unclear. We investigated the expression of all C-type lectins during JEV infection inAedes aegyptiThe C-type lectin mosquito galactose-specific C-type lectin 7 (mosGCTL-7) (VectorBase accession no. AAEL002524) was significantly upregulated by JEV infection and facilitated infectionin vivoandin vitromosGCTL-7 bound to the N-glycan at N154 on the JEV envelope protein. This recognition of viral N-glycan by mosGCTL-7 is required for JEV infection, and we found that this interaction was Ca2+dependent. After mosGCTL-7 bound to the glycan, mosPTP-1 bound to mosGCTL-7, promoting JEV entry. The viral burdenin vivoandin vitrowas significantly decreased by mosPTP-1 double-stranded RNA (dsRNA) treatment, and infection was abolished by anti-mosGCTL-7 antibodies. Our results indicate that the mosGCTL-7/mosPTP-1 pathway plays a key role in JEV infection in mosquitoes. An improved understanding of the mechanisms underlying flavivirus infection in mosquitoes will provide further opportunities for developing new strategies to control viral dissemination in nature.IMPORTANCEJapanese encephalitis virus is a mosquito-borne flavivirus and is the primary cause of viral encephalitis in the Asia-Pacific region. Twenty-four countries in the WHO Southeast Asia and Western Pacific regions have endemic JEV transmission, which exposes >3 billion people to the risks of infection, although JEV primarily affects children. C-type lectins are host factors that play a role in flavivirus infection in humans, swine, and other mammals. In this study, we investigated C-type lectin functions in JEV-infectedAedes aegyptiandCulex pipiens pallensmosquitoes and cultured cells. JEV infection changed the expression of almost all C-type lectinsin vivoandin vitro, and mosGCTL-7 bound to the JEV envelope protein via an N-glycan at N154. Cell surface mosPTP-1 interacted with the mosGCTL-7-JEV complex to facilitate virus infectionin vivoandin vitroOur findings provide further opportunities for developing new strategies to control arbovirus dissemination in nature.
authors.affiliation: Key Laboratory of Animal Disease Diagnostic and Immunology, Department of Veterinary Medicine College, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.|Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Disease Diagnostic and Immunology, Department of Veterinary Medicine College, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yingjuan
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Key Laboratory of Animal Disease Diagnostic and Immunology, Department of Veterinary Medicine College, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yong-Sam
authors.initials: YS
authors.lastname: Jung
authors.affiliation: Key Laboratory of Animal Disease Diagnostic and Immunology, Department of Veterinary Medicine College, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Disease Diagnostic and Immunology, Department of Veterinary Medicine College, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Ruibing
authors.initials: R
authors.lastname: Cao
authors.affiliation: Key Laboratory of Animal Disease Diagnostic and Immunology, Department of Veterinary Medicine College, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Shen
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Donghua
authors.initials: D
authors.lastname: Shao
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Wei
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Key Laboratory of Animal Disease Diagnostic and Immunology, Department of Veterinary Medicine College, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China puyanchennj@yeah.net hmzhu@hotmail.com.
authors.forename: Puyan
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology, Second Military Medical University, Shanghai, People's Republic of China puyanchennj@yeah.net hmzhu@hotmail.com.
authors.forename: Huaimin
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000330:Aedes / Q000737:chemistry* / Q000821:virology*; D000818:Animals; D002460:Cell Line; D003465:Culex / Q000737:chemistry* / Q000821:virology*; D004664:Encephalitis Virus, Japanese / Q000502:physiology*; D004672:Encephalitis, Japanese / Q000503:physiopathology / Q000635:transmission / Q000821:virology; D054884:Host-Pathogen Interactions; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000378:metabolism; D019562:Viral Load; D053586:Virus Internalization
chemical_list: D037181:Lectins, C-Type; D012330:RNA, Double-Stranded; D014759:Viral Envelope Proteins
keywords: C-type lectin; Japanese encephalitis virus; virus entry