Variation in interferon sensitivity and induction between Usutu and West Nile (lineages 1 and 2) viruses

- USUV can replicate in DCs as both WNVs (L1 and L2).
- USUV induces a higher activation of IFN-associated antiviral immune response than both WNVs (L1 and L2).
- USUV is more sensitive to types I and III IFN than both WNVs (L1 and L2).
- The ability of WNV L2 to replicate in DCs and promote the induction of IFN alpha subtypes and ISG responses, as well as the inhibition of IFN lambda 1-3, did not differ from that of WNV L1.

Given the pivotal role of monocyte-derived dendritic cells (DCs) in determining the magnitude of the antiviral innate immune response, we sought to determine whether Usutu virus (USUV) and West Nile virus (WNV) lineages (L)1 and L2 can infect DCs and affect the rate of type I interferon (IFN) activation. The sensitivity of these viruses to types I and III IFNs was also compared. We found that USUV can infect DCs, induce higher antiviral activities, IFN alpha subtypes and the IFN stimulated gene (ISG)15 pathway, and is more sensitive to types I and III IFNs than WNVs. In contrast, we confirmed that IFN alpha/beta subtypes were more effective against WNV L2 than WNV L1. However, the replication kinetics, induction of IFN alpha subtypes and ISGs in DCs and the sensitivity to IFN lambda 1-3 did not differ between WNV L1 and L2.