Xiao Chai Hu Tang inhibits CVB 1 virus infection of CCFS-1 cells through the induction of Type I interferon expression

Abstract

Coxsackie B virus type 1 (CVB 1) infection is known to cause high morbidity and mortality in children, however, there is no effective drug for treating this disease. The present study aimed to examine the antiviral activity of Xiao Chai Hu Tang (XCHT), a popular herbal drug for treating viral and bacterial infections, against CVB 1 infection and its mechanisms of action. Our data showed that XCHT neutralized the CVB 1-induced cytopathic effect in human neonatal foreskin fibroblast cell line (CCFS-1/KMC), with IC 50 (virus-induced cytopathic effect by 50%) and EC 50 (concentration of 50% effectiveness) values around 12.39 and 50.93 μg/ml, respectively. Its CC 50 (concentration of 50% cellular cytotoxicity) and SI (selective index) values were 945.75 μg/ml and 18.92, respectively. These results suggest that XCHT possessed anti-CVB 1 activity, and showed no effect on CCFS-1 cell viability and growth at concentration 250 μg/ml. The time-of-addition studies showed that XCHT (50, 100 and 200 μg/ml) added at various time of preinfection (− 1 to − 3 h), coinfection (0 h) and postinfection (1∼3 h) could inhibit CVB 1 infection. Interestingly, XCHT also showed an inhibition on viral replication through the induction of IFN-α/β expression. In conclusion, XCHT possessed antiviral activity against CVB 1 infection. It interfered the early stage of viral replication (prophylactic effect) and viral replication after infection (therapeutic effect) through the induction of Type I interferon expression.