title: Phenoloxidase activity acts as a mosquito innate immune response against infection with Semliki Forest virus.
abstract: Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses.
authors.affiliation: The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, United Kingdom.
authors.forename: Julio
authors.initials: J
authors.lastname: Rodriguez-Andres
authors.forename: Seema
authors.initials: S
authors.lastname: Rani
authors.forename: Margus
authors.initials: M
authors.lastname: Varjak
authors.forename: Margo E
authors.initials: ME
authors.lastname: Chase-Topping
authors.forename: Markus H
authors.initials: MH
authors.lastname: Beck
authors.forename: Mhairi C
authors.initials: MC
authors.lastname: Ferguson
authors.forename: Esther
authors.initials: E
authors.lastname: Schnettler
authors.forename: Rennos
authors.initials: R
authors.lastname: Fragkoudis
authors.forename: Gerald
authors.initials: G
authors.lastname: Barry
authors.forename: Andres
authors.initials: A
authors.lastname: Merits
authors.forename: John K
authors.initials: JK
authors.lastname: Fazakerley
authors.forename: Michael R
authors.initials: MR
authors.lastname: Strand
authors.forename: Alain
authors.initials: A
authors.lastname: Kohl
mesh_terms: D000330:Aedes / Q000276:immunology / Q000821:virology; D018354:Alphavirus Infections / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D007113:Immunity, Innate; D019476:Insect Proteins / Q000276:immunology*; D014442:Monophenol Monooxygenase / Q000276:immunology*; D012672:Semliki forest virus / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D019476:Insect Proteins; D014442:Monophenol Monooxygenase