title: Comparison of attenuated and virulent West Nile virus strains in human monocyte-derived dendritic cells as a model of initial human infection.
abstract: BACKGROUND
  The human-pathogenic North American West Nile virus strain (WNVNY99), responsible for the outbreak in New York city in 1999, has caused 41000 infections and 1739 human deaths to date. A new strain of West Nile virus emerged in New South Wales, Australia in 2011 (WNVNSW2011), causing a major encephalitic outbreak in horses with close to 1000 cases and 10-15% mortality. Unexpectedly, no human cases have so far been documented.
  
  
  RESULTS
  We report here, using human monocyte-derived dendritic cells (MoDCs) as a model of initial WNV infection, that the pathogenic New York 99 WNV strain (WNVNY99) replicated better than WNVNSW2011, indicative of increased viral dissemination and pathogenesis in a natural infection. This was attributed to suppressed viral replication and type I interferon (IFN) response in the early phase of WNVNY99 infection, leading to enhanced viral replication at the later phase of infection. In addition, WNVNY99 induced significantly more pro-inflammatory cytokines in MoDCs compared to WNVNSW2011.
  
  
  CONCLUSIONS
  Our results suggest that the observed differences in replication and induction of IFN response between WNVNY99 and WNVNSW2011 in MoDCs may be indicative of their difference in virulence for humans.
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, 4072, QLD, Australia. d.rawle@uq.edu.au.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rawle
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, 4072, QLD, Australia. y.setoh@uq.edu.au.
authors.forename: Yin Xiang
authors.initials: YX
authors.lastname: Setoh
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, 4072, QLD, Australia. j.edmonds1@uq.edu.au.
authors.forename: Judith H
authors.initials: JH
authors.lastname: Edmonds
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, 4072, QLD, Australia. alexander.khromykh@uq.edu.au.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Khromykh
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication; D014901:West Nile Fever / Q000662:veterinary / Q000821:virology*; D014902:West Nile virus / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D007372:Interferons