Severe fever with thrombocytopenia syndrome virus (SFTSV) is a negative-sense RNA virus that can cause high fever, thrombocytopenia, and multiple-organ dysfunction. Toll-like receptor 7 (TLR7) can recognize single-stranded RNA viruses and induce type I interferons (IFNs). Although type I IFNs play a critical role in SFTSV infection, the role of TLR7 remains incompletely understood. To investigate the role of TLR7 signaling in SFTSV pathogenesis, TLR7-deficient (TLR7 −/− ) mice and wild-type (WT) mice were inoculated with SFTSV. TLR7 −/− mice exhibited severe weight loss and elevated viral RNA levels in various organs compared to WT mice. These mice also showed marked white pulp atrophy in the spleen and increased immunoreactivity for SFTSV nucleoprotein antigen. To further assess the significance of TLR7 signaling, resiquimod (R848), a TLR7 agonist was administered to SFTSV-infected mice. R848-treated mice exhibited significantly reduced viral loads in multiple organs and showed decreased levels of tumor necrosis factor alpha and interleukin-1 beta in the spleen and serum compared to mice in the control group. Consistently, R848-treated mice presented with mild white pulp atrophy and reduced antigen reactivity to the SFTSV nucleoprotein in the spleen. Collectively, modulation of TLR7 signaling, demonstrated by R848 activation and TLR7 deficiency, provides a novel approach to regulating antiviral immune responses against SFTSV infection.
Ham et al. (Wed,) studied this question.