Although dermal fibroblasts are one of the first cell types exposed to West Nile virus (WNV) during a blood meal by an infected mosquito, little is known about WNV replication within this cell type. Here, I demonstrate that pathogenic, WNV-New York (WNV-NY), and nonpathogenic, WNV-Australia (WNV-AUS60) strains are able to infect and replicate in primary human dermal fibroblasts (HFFs). However, WNV-AUS60 replication and spread within HFFs was reduced compared to that of WNV-NY due to an interferon-independent reduction in viral infectivity early in infection. Additionally, replication of both strains was constrained late in infection by an IFN-β-dependent reduction in particle infectivity. Overall, our data indicate that dermal fibroblasts are capable of supporting WNV replication; however, the low infectivity of particles produced from HFFs late in infection suggests that this cell type likely plays a limited role as a viral reservoir in vivo
