Heat shock protein 60 manipulates Foot-and-Mouth disease virus replication by regulating mitophagy.

Abstract

Mitochondria serve as the hubs of cellular signaling, energetics, and redox balance under physiological conditions. Mitochondria play an essential role in defending against pathogenic infections upon virus invasion. As a critical intracellular physiological process, mitophagy is crucial for maintaining mitochondrial homeostasis. Accumulating evidence suggests that mitophagy contributes to modulating viral infection. In our previous study, we reported that heat shock protein 60 (HSP60) is involved in orchestrating autophagy; however, the underlying mechanisms remain elusive. Here, we examined the role of HSP60 in priming mitophagy to regulate foot-and-mouth disease virus (FMDV) replication. We first reported that mitophagy was elicited post-FMDV infection and further restricted FMDV replication. Regarding HSP60, our results showed that HSP60 depletion triggered Parkin-dependent mitophagy via activating dynamin-related protein 1 (Drp1) phosphorylation at Ser616 and promoting Drp1 translocation to mitochondria. Furthermore, calmodulin-dependent protein kinase II (CaMKII) was essential for phosphorylating Drp1 at Ser616 in HSP60-depleted cells. Taken together, HSP60 manipulates FMDV replication by governing mitophagy. Importantly, HSP60 could be a promising antiviral target for controlling FMDV infection.