Comparison of attenuated and virulent West Nile virus strains in human monocyte-derived dendritic cells as a model of initial human infection

BACKGROUND: The human-pathogenic North American West Nile virus strain (WNV(NY99)), 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 (WNV(NSW2011)), 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. FINDINGS: 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 (WNV(NY99)) replicated better than WNV(NSW2011), 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 WNV(NY99) infection, leading to enhanced viral replication at the later phase of infection. In addition, WNV(NY99) induced significantly more pro-inflammatory cytokines in MoDCs compared to WNV(NSW2011). CONCLUSIONS: Our results suggest that the observed differences in replication and induction of IFN response between WNV(NY99) and WNV(NSW2011) in MoDCs may be indicative of their difference in virulence for humans.