West Nile virus-induced cytoplasmic membrane structures provide partial protection against the interferon-induced antiviral MxA protein.
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.
Hoenen
Antje
A
School of Molecular and Microbial Sciences, University of Queensland, St Lucia, Queensland, Australia.
Liu
Wenjun
W
School of Molecular and Microbial Sciences, University of Queensland, St Lucia, Queensland, Australia.
Kochs
Georg
G
Department of Virology, University of Freiburg, Freiburg, Germany.
Khromykh
Alexander A
AA
School of Molecular and Microbial Sciences, University of Queensland, St Lucia, Queensland, Australia.
Mackenzie
Jason M
JM
School of Molecular and Microbial Sciences, University of Queensland, St Lucia, Queensland, Australia.
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*
D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins