title: Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection.
abstract: Aedes aegypti mosquitoes are responsible for transmitting many medically important viruses such as those that cause Zika and dengue. The inoculation of viruses into mosquito bite sites is an important and common stage of all mosquito-borne virus infections. We show, using Semliki Forest virus and Bunyamwera virus, that these viruses use this inflammatory niche to aid their replication and dissemination in vivo. Mosquito bites were characterized by an edema that retained virus at the inoculation site and an inflammatory influx of neutrophils that coordinated a localized innate immune program that inadvertently facilitated virus infection by encouraging the entry and infection of virus-permissive myeloid cells. Neutrophil depletion and therapeutic blockade of inflammasome activity suppressed inflammation and abrogated the ability of the bite to promote infection. This study identifies facets of mosquito bite inflammation that are important determinants of the subsequent systemic course and clinical outcome of virus infection.
authors.affiliation: Virus Host Interaction Team, Section of Infection and Immunity, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
authors.forename: Marieke
authors.initials: M
authors.lastname: Pingen
authors.affiliation: Virus Host Interaction Team, Section of Infection and Immunity, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK; Institute of Infection, Immunology and Inflammation, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Bryden
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: Emilie
authors.initials: E
authors.lastname: Pondeville
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: Esther
authors.initials: E
authors.lastname: Schnettler
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: Alain
authors.initials: A
authors.lastname: Kohl
authors.affiliation: Institute of Technology, University of Tartu, 50411 Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Merits
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, UK.
authors.forename: John K
authors.initials: JK
authors.lastname: Fazakerley
authors.affiliation: Institute of Infection, Immunology and Inflammation, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Graham
authors.affiliation: Virus Host Interaction Team, Section of Infection and Immunity, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK. Electronic address: c.s.mckimmie@leeds.ac.uk.
authors.forename: Clive S
authors.initials: CS
authors.lastname: McKimmie
mesh_terms: D000818:Animals; D001102:Arbovirus Infections / Q000276:immunology*; D002042:Bunyamwera virus / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D009033:Culicidae / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000821:virology; D007299:Insect Bites and Stings / Q000276:immunology* / Q000821:virology; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000821:virology; D012672:Semliki forest virus / Q000502:physiology*; D014779:Virus Replication
chemical_list: D058847:Inflammasomes