Research of simvastatin-induced autophagy in inhibiting recombinant human metapneumovirus replication / 中华微生物学和免疫学杂志

ABSTRACT

Objective:To study whether simvastatin could inhibit viral replication during human metapneumovirus (hMPV) infection.Methods:Human bronchial epithelial cells (16HBE) were infected with hMPV and then treated with or without simvastatin. Real-time quantitative PCR (qPCR) and Western blot were used to detect virus titers and the activation of autophagy and related pathways. BALB/c mice were infected with hMPV and then treated with simvastatin through intragastric administration. Pathological changes in lung tissues were observed. Changes in viral loads and the activation of autophagy and related pathways in proteins and RNA extracted from lung tissues were detected.Results:The in vitro experiment showed that the hMPV+ simvastatin group had decreased virus titer and enhanced autophagy than the hMPV group. The AKT/mTOR pathway in the hMPV+ simvastatin group was inhibited, which was verified by a further experiment using rapamycin, a specific inhibitor of AKT/mTOR pathway. The in vivo experiment showed that the virus titer in the hMPV+ simvastatin group was lower than that in the hMPV group, but there was no significant difference in the activation of autophagy. The AKT/mTOR pathway was down-regulated in the hMPV+ simvastatin group. HE staining revealed that obvious pathological changes were observed in the hMPV group, but the condition was improved after simvastatin intervention. Conclusions:Simvastatin can inhibit the replication of hMPV, which is associated with the activation of autophagy induced by AKT/mTOR pathway.