Resistance to Alpha/Beta Interferon Is a Determinant of West Nile Virus Replication Fitness and Virulence

摘要: The emergence of West Nile virus (WNV) in the Western Hemisphere is marked by spread pathogenic lineage I strains, which differ from typically avirulent II strains. To begin to understand virus-host interactions that may influence phenotypic properties divergent and viruses, we compared genetic, pathogenic, alpha/beta interferon (IFN-alpha/beta)-regulatory a isolate Madagascar (MAD78) with those new Texas (TX02). Full genome sequence analysis revealed MAD78 clustered, albeit distantly, other while TX02 clustered emergent North American isolates, more specifically Compared TX02, replicated at low levels cultured human cells, was highly sensitive antiviral actions IFN vitro, demonstrated completely phenotype wild-type mice. In contrast forms WNV, defective its ability disrupt IFN-induced JAK-STAT signaling, including activation Tyk2 downstream phosphorylation nuclear translocation STAT1 STAT2. However, replication rescued cells nonfunctional IFN-alpha/beta receptor (IFNAR). Consistent this finding, virulence unmasked upon infection mice lacking IFNAR. Thus, control innate host response key feature WNV pathogenesis fitness.