title: Insect-specific flavivirus infection is restricted by innate immunity in the vertebrate host.
abstract: Arboviruses are a large group of viruses that are transmitted by arthropods including ticks and mosquitoes. The global diversity of arboviruses is unknown; however, theoretical studies have estimated that over 2,000 mosquito-borne flaviviruses may exist. An increasing number of flaviviruses can only infect insect cells. We hypothesize that insect-specific flaviviruses (ISFVs) represent model genetic precursors to pathogenic flaviviruses, although the genetic mechanisms required for adaptation to vertebrate hosts are unclear. In this study, we determined that Kamiti River virus (KRV) infection was inhibited by innate immunity pathways in vertebrate cells. KRV infection of IRF3,5,7(-/-) mouse embryonic fibroblasts led to low levels of viral protein production and shedding of infectious progeny. These data suggest that ISFVs cannot evade vertebrate innate immune pathways. Identifying cellular pathways and genetic changes that are required for adaptation of arthropod-specific arboviruses to vertebrate hosts is critical to understanding emerging infectious disease.
authors.affiliation: Foundational Sciences, Central Michigan University College of Medicine, Mt. Pleasant, MI, United States.
authors.forename: Maya O
authors.initials: MO
authors.lastname: Tree
authors.affiliation: Foundational Sciences, Central Michigan University College of Medicine, Mt. Pleasant, MI, United States.
authors.forename: Dexter R
authors.initials: DR
authors.lastname: McKellar
authors.affiliation: Foundational Sciences, Central Michigan University College of Medicine, Mt. Pleasant, MI, United States.
authors.forename: Kristopher J
authors.initials: KJ
authors.lastname: Kieft
authors.affiliation: Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Watson
authors.affiliation: Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Kate D
authors.initials: KD
authors.lastname: Ryman
authors.affiliation: Foundational Sciences, Central Michigan University College of Medicine, Mt. Pleasant, MI, United States. Electronic address: michael.conway@cmich.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Conway
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D005075:Biological Evolution; D002460:Cell Line; D002522:Chlorocebus aethiops; D005416:Flavivirus / Q000502:physiology*; D018177:Flavivirus Infections / Q000276:immunology* / Q000635:transmission / Q000821:virology*; D055786:Gene Knockout Techniques; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007303:Insect Vectors / Q000821:virology*; D007313:Insecta / Q000821:virology*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D014714:Vertebrates; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D050835:Interferon Regulatory Factors; D034741:RNA, Small Interfering; D012367:RNA, Viral; D051196:Toll-Like Receptor 3; D014764:Viral Proteins
keywords: Dengue virus; Evolution; Flavivirus; Host adaptation; Innate immunity; Insect-specific; Kamiti River virus