Coxsackievirus B4 uses autophagy for replication after calpain activation in rat primary neurons.

Coxsackievirus is the most important cause of meningitis and encephalitis in infants; an infection is sometimes fatal or may lead to neurodevelopmental defects. Here, we show that coxsackievirus B4 (CVB4) induces an autophagy pathway for replication in rat primary neurons. Notably, calpain inhibitors reduce autophagosome formation. Conversely, the inhibition of the autophagy pathway with 3-methyladenine inhibits calpain activation. This work reveals, for the first time, that calpain is essential for the autophagy pathway and viral replication in CVB4-infected neurons.