In vitro and in vivo characterization of a West Nile virus MAD78 infectious clone

The viral determinants governing the varied neuropathogenicity of different West Nile virus (WNV) strains are poorly understood. Here, we generated an infectious clone (WNV-MADIC) of the non-pathogenic strain WNV-MAD78 and compared its replication to that of parental WNV-MAD78 and a WNV-MAD78 infectious clone (WNV-MADTX-UTRs) containing the 5′ and 3′ untranslated regions (UTRs) of the pathogenic strain WNV-TX. All three viruses replicated at similar rates and caused similar lethality in mice. Thus, the infectious clone is indistinguishable from parental virus in replication and neurovirulence, and the UTRs alone do not account for the increased virulence of WNV-TX compared to WNV-MAD78.