Rapamycin and ZSTK474 can have differential effects at different post‑infection time‑points regarding CVB3 replication and CVB3‑induced autophagy.

Abstract

Coxsackievirus B3 (CVB3) infection has been shown to stimulate autophagy. We have demonstrated that the inhibition of phosphoinositide 3‑kinase (PI3K)/protein kinase B/mammalian target of rapamycin complex (mTORC) signaling pathway could affect the autophagic reaction induced by CVB3 infection in our previous study. However, the processes associating autophagy and CVB3 replication remain to be determined. In the present study, CVB3‑induced autophagy and its impact on viral replication were investigated. Rapamycin (inhibitor of mTOR) and ZSTK474 (inhibitor of PI3K) were used to change the autophagic reaction caused by CVB3 in Hela cells at different post‑infection (p.i.) time points (6, 9, 12 and 24h p.i.), meanwhile, we detected the CVB3 mRNA replication and CVB3 capsid protein VP1 expression following the change of autophagy. Here, it was showed that ZSTK474 and Rapamycin promoted CVB3‑induced autophagy, as well as decreasing CVB3 mRNA replication and CVB3 capsid protein VP1 expression at 6 and 9h p.i. ZSTK474 also alleviated CVB3‑induced autophagy, and decreased CVB3 mRNA replication and VP1 expression at 12 and 24h p.i. However, Rapamycin continued to promote CVB3‑induced autophagy and increase CVB3 mRNA replication at 12 and 24h p.i, as well as increase VP1 expression at 12h, but not at 24h, p.i. In the present study, we found Rapamycin and ZSTK474 have differential effects at different p.i. time‑points regarding CVB3 replication and CVB3‑induced autophagy. This indicates that the association between CVB3‑induced autophagy and viral replication depends on the infection time. During the early course of infection, autophagy may help host cells clear the virus, thereby providing protection, whereas when the infection time increases, autophagy may be exploited for viral replication.