Knockdown of METTL3 inhibits enterovirus 71 induced apoptosis of mouse Schwann cell through regulation of autophagy.

Abstract

Enterovirus A71 (EV-A71 or EV-71) is an RNA virus which cause hand, foot and mouse disease (HFMD) in children. The N6-methyladenosine (m6A) of RNA is a common RNA modification involved in various biological events. METTL3 is an m6A methyltransferase which regulates EV-71 replication. EV-71 infection induces autophagy, which promotes EV-71 replication too. In this study, we explored the role of METTL3 in EV-71 infection-induced autophagy. We constructed lentivirus expressing METTL3 specific shRNA and knocked down the endogenous METTL3 in mouse Schwann cells. We infected normal Schwann cells and METTL3 knock down Schwann cells and compared the viral titer, expression of autophagy-related proteins and apoptosis-related protein. Transduction of lentivirus expressing METTL3 shRNA significantly decreased the endogenous METTL3. Knocking down METTL3 decreased the viral titer of EV-71 after infection. Knocking down METTL3 prevented EV-71 induced cell death and suppressed EV-71-induced expression of Bax while rescued Bcl-2 expression after EV-71 infection. Knocking down METTL3 inhibited EV-71-induced expression of Atg5, Atg7 and LC3 II. Knocking down METTL3 inhibited EV-71 induced apoptosis and autophagy. In summary, our study described the relation of METTL3 and autophagy during EV-71 infection.