Toll-Like Receptor 8 Signaling Facilitates West Nile Virus Infection in Mice (VIR9P.1161)
West Nile virus (WNV) is a neurotropic virus that can cause encephalitis, meningitis or possible death in humans. Human and mouse Toll-like receptor 7 (h/mTLR7) and human Toll-like receptor 8 (hTLR8) detect viral single-stranded (ss)RNA motifs. Importantly, mTLR7 recognizes WNV, as TLR7-/- mice are susceptible to lethal WNV infection. However, the role of TLR8 in WNV pathogenesis is not clear. In this study, we found that mice deficient in TLR8 (TLR8-/-) infected with WNV (2,000 plaque forming units) had improved percentage survival (65%) compared to wild-type (WT) controls (25%), which was coupled to reduced viral burden in the brains of TLR8-/- mice. These data suggest that TLR8 signaling facilities WNV infection in mice. Further mechanistic studies showed that expression of TLR7 and the interferon-induced anti-viral gene Isg-56 (IFIT-1) were significantly increased in TLR8-/- mice whole-brain samples and mixed neuronal cultures following WNV infection, compared to WT controls. These results indicate that TLR8 signaling may down-regulate TLR7 and Isg-56 expression, thus promoting WNV-induced neuroinvasive disease.
The Journal of Immunology
Paul, A. M.,
Stokic, D. S.,
(2015). Toll-Like Receptor 8 Signaling Facilitates West Nile Virus Infection in Mice (VIR9P.1161). The Journal of Immunology, 194(1S).
Available at: https://aquila.usm.edu/fac_pubs/15121