Effect of TSS on anti-CVB3 through TLR3 pathway

Abstract

ABSTRACTToll-like receptors (TLRs) can recognize molecular patterns associated with microorganisms and induce immune responses. TLR3 is responsible for recognizing viruses and making hosts resistant to Coxsackie B3 (CVB3) infection. In this study, we found that Tectorigenin Sodium Sulfonate (TSS) has a TLR3 inhibitory effect and exerts strong anti-CVB3 activity through the TLR3 pathway both in vivo and in vitro. Balb/c mice were infected by ip injection of CVB3 virus, and subcutaneously injected with TSS at 264mg·Kg-1·d-1 for 7 d. The life extension rate of CVB3-infected mice was up to 46.67%, and the mean time to death was prolonged from 6.00 ± 0.47 d to 8.80 ± 2.78 d (P < 0.01). TSS was also able to reduce the level of weight loss in mice, significantly reduce the symptoms of myocarditis caused by CVB3, reduce the virus titer in the heart, improve the spleen and thymus index, and enhance immune function. We further explored the underlying mechanism of TSS in CVB3-infected HT-29 cells and mice: TSS reduced TLR3 expression and downregulated its downstream TRIF, TRAF6, IRF3, NF-κ B. MAPK, AP1 expression, reduced expression of IFN-β、IL-6、TNF-α. TSS has strong anti-CVB3 activity in vitro and in vivo and has the effect of inhibiting the activation of TLR3 pathway.IMPORTANCETSS is expected to be an antiviral drug for the treatment of CVB3 infection. Its regulatory effect on the immune system provides a new approach for antiviral research.