title: Aedes aegypti ML and Niemann-Pick type C family members are agonists of dengue virus infection.
abstract: Upon exposure to dengue virus, the Aedes aegypti mosquito vector mounts an anti-viral immune defense by activating the Toll, JAK/STAT, and RNAi pathways, thereby limiting infection. While these pathways and several other factors have been identified as dengue virus antagonists, our knowledge of factors that facilitate dengue virus infection is limited. Previous dengue virus infection-responsive transcriptome analyses have revealed an increased mRNA abundance of members of the myeloid differentiation 2-related lipid recognition protein (ML) and the Niemann Pick-type C1 (NPC1) families upon dengue virus infection. These genes encode lipid-binding proteins that have been shown to play a role in host-pathogen interactions in other organisms. RNAi-mediated gene silencing of a ML and a NPC1 gene family member in both laboratory strain and field-derived Ae. aegypti mosquitoes resulted in significantly elevated resistance to dengue virus in mosquito midguts, suggesting that these genes play roles as dengue virus agonists. In addition to their possible roles in virus cell entry and replication, gene expression analyses suggested that ML and NPC1 family members also facilitate viral infection by modulating the mosquito's immune competence. Our study suggests that the dengue virus influences the expression of these genes to facilitate its infection of the mosquito host.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe St., Baltimore, MD 21205, USA.
authors.forename: Natapong
authors.initials: N
authors.lastname: Jupatanakul
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe St., Baltimore, MD 21205, USA.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Sim
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe St., Baltimore, MD 21205, USA. Electronic address: gdimopou@jhsph.edu.
authors.forename: George
authors.initials: G
authors.lastname: Dimopoulos
mesh_terms: D000330:Aedes / Q000276:immunology* / Q000821:virology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019223:Densovirinae / Q000502:physiology*; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D051218:Lymphocyte Antigen 96 / Q000235:genetics; D010322:Parvoviridae Infections / Q000276:immunology*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D019476:Insect Proteins; C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; D034741:RNA, Small Interfering; D051192:Receptors, Pattern Recognition
keywords: Aedes aegypti; Dengue virus; Myeloid differentiation 2-related lipid recognition gene; Niemann Pick-type C gene