title: West Nile virus NS2A protein facilitates virus-induced apoptosis independently of interferon response.
abstract: The flavivirus NS2A protein is a small, multifunctional protein, involved in replication, virion formation and regulation of the innate immune response. Using the Kunjin strain of West Nile virus (WNV(KUN)) we previously demonstrated that a single amino acid change from alanine to proline at position 30 of the NS2A protein (A30P) reduced viral cytopathicity in cells and virulence in mice. To further investigate functions of the NS2A protein we have substituted alanine at position 30 with different amino acids (A30 mutants) in a WNV(KUN) infectious clone. The virulence of mutant viruses in wild-type (WT) and IRF3/IRF7 double-knockout mice was influenced by the amino acid change and ranged from high to low in the order of WT>A30L>A30E>A30P/A30G. Moreover, infection of beta interferon (IFN-β)-deficient Vero cells with A30P virus showed less pronounced chromosomal DNA degradation and lower percentage of cells with positive TUNEL labelling than in WT virus infection, indicating a role for the WT NS2A protein in IFN-independent apoptotic cell death.
authors.affiliation: Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Ezequiel Balmori
authors.initials: EB
authors.lastname: Melian
authors.affiliation: Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Judith H
authors.initials: JH
authors.lastname: Edmonds
authors.affiliation: Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Tomoko Kim
authors.initials: TK
authors.lastname: Nagasaki
authors.affiliation: Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Edward
authors.initials: E
authors.lastname: Hinzman
authors.affiliation: Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Floden
authors.affiliation: Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Khromykh
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D007372:Interferons / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D014901:West Nile Fever / Q000473:pathology / Q000821:virology; D014902:West Nile virus / Q000472:pathogenicity*
chemical_list: D050505:Mutant Proteins; D017361:Viral Nonstructural Proteins; D037521:Virulence Factors; D007372:Interferons