title: West Nile virus-induced cytoplasmic membrane structures provide partial protection against the interferon-induced antiviral MxA protein.
abstract: The human MxA protein is a type I and III interferon (IFN)-induced protein with proven antiviral activity against RNA viruses. In this study, we investigated the effect of MxA expression on the replication of West Nile Virus strain Kunjin (WNV(KUN)). Pretreatment of A549 cells with IFN-alpha lead to increased expression of MxA, which contributed to inhibition of WNV(KUN) replication and secretion. However, in Vero cells stably expressing the MxA protein, WNV(KUN) replication, maturation and secretion was not inhibited. Biochemical and subcellular localization studies of WNV(KUN) proteins and MxA suggest that the MxA activity was not compromised by a flavivirus-encoded antagonist. Instead, we show that characteristic membranous structures induced during WNV(KUN) replication provide partial protection from MxA, possibly by 'hiding' WNV(KUN) replication components. This distinct compartmentalization of viral replication and components of the cellular antiviral response may be an evolutionary mechanism by which flaviviruses can hide from host surveillance.
authors.affiliation: School of Molecular and Microbial Sciences, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Antje
authors.initials: A
authors.lastname: Hoenen
authors.affiliation: School of Molecular and Microbial Sciences, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Virology, University of Freiburg, Freiburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Kochs
authors.affiliation: School of Molecular and Microbial Sciences, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Khromykh
authors.affiliation: School of Molecular and Microbial Sciences, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Mackenzie
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000821:virology*; D002522:Chlorocebus aethiops; D019204:GTP-Binding Proteins / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D064547:Myxovirus Resistance Proteins; D014902:West Nile virus / Q000254:growth & development / Q000276:immunology*
chemical_list: D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins