Saikosaponin D, a novel autophagy inhibitor, potently inhibited Enterovirus 71(EV71)- induced cell death

Abstract

Autophagy is a conserved physiological process which degrades misfolded cellular proteins and damaged organelles for cell survival. Enterovirus 71 (EV71) is a major agent of hand, foot and mouth disease in children that can cause severe central nervous system disease. Defective autophagy is associated with a number of diseases. As intracellular parasites, during the course of an infection, viruses encounter autophagy and interact with the proteins that execute this process. Autophagy serves either as an antiviral defense mechanism or, alternatively, as a pro-viral process during virus infection. We previous found that Saikosaponin D is a potent autophagy inhibitor. Now, we found that Saikosaponin D could inhibit EV71-induced cell death in a concentration-dependent manner in Hela cells. Also, EV71 could induce autophagy. Rapamycin, a well known autophagy inducer, enhanced EV-71 induced autophagy and increased VP1 (virus coat protein) production, then promoted cell death after EV71 infection. Furthermore, VP1 production decreased after EV71 infection in ATG5 knockdown Hela cells. Thus, autophagy play important role in EV71 infection. We are currently exploring the mechanisms underlying anti-virus function of Saikosaponin D and exact role of autophagy in EV71 infection process.