A Hamster-derived West Nile Virus Strain is Highly Attenuated and Induces a Differential Proinflammatory Cytokine Response in Two Murine Cell Lines

Increasing evidence suggests that West Nile virus (WNV) induces a persistent infection in some humans and animals. Here, we characterized infection of mouse macrophage and kidney epithelial cell lines with a strain of WNV (H8912), cultured from urine of a persistently infected hamster. WNV H8912 had a reduced replication rate, concurrent with a lower interferon (IFN)-β gene expression in both cell types compared to its parent strain - WNV NY99. In WNV H8912-infected macrophages, we observed higher interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression and more nuclear factor kappa B (NF-κB) activation than in cells infected with WNV NY99. In contrast, there were reduced levels of TNF-α and IL-6 expression, as well as less NF-κB activation following WNV H8912 infection in the kidney epithelial cells compared to WNV NY99. Overall, our results demonstrate that the WNV isolate obtained from hamster urine is an attenuated virus and induces a differential proinflammatory cytokine response in mouse macrophage and kidney epithelial cell lines.