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Updated: May 17, 2025
Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods
Published on: December 21, 2019
Heat shock protein 60 manipulates Foot-and-Mouth disease virus replication by regulating mitophagy
Jianli Tang1,2, Sahibzada Waheed Abdullah1,2, Shiqi Sun1,2
1State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
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.
Insights
Heat shock protein 60 (HSP60) regulates mitophagy, a process crucial for controlling viral infections. HSP60 depletion activates mitophagy, restricting foot-and-mouth disease virus (FMDV) replication, suggesting HSP60 as an antiviral target.
Area of Science:
- Cell Biology
- Virology
- Immunology
Background:
- Mitochondria are vital for cellular functions, including defense against viral pathogens.
- Mitophagy, the selective degradation of mitochondria, is essential for maintaining mitochondrial health and impacts viral infections.
- Heat shock protein 60 (HSP60) has been implicated in autophagy, but its role in mitophagy and viral regulation is unclear.
Purpose of the Study:
- To investigate the role of HSP60 in mitophagy.
- To determine how HSP60 influences foot-and-mouth disease virus (FMDV) replication.
- To elucidate the molecular mechanisms by which HSP60 regulates mitophagy in response to viral infection.
Main Methods:
- FMDV infection in cell culture models.
- HSP60 depletion using RNA interference or genetic manipulation.
- Analysis of mitophagy markers and mitochondrial dynamics.
- Western blotting to detect protein phosphorylation and translocation (e.g., Drp1 phosphorylation at Ser616).
- Assessment of FMDV replication levels.
Main Results:
- FMDV infection elicits mitophagy, which restricts viral replication.
- HSP60 depletion enhances Parkin-dependent mitophagy.
- HSP60 depletion promotes dynamin-related protein 1 (Drp1) phosphorylation at Ser616 and its mitochondrial translocation.
- Calmodulin-dependent protein kinase II (CaMKII) is required for Drp1 phosphorylation in HSP60-depleted cells.
Conclusions:
- HSP60 plays a critical role in governing mitophagy and consequently influences FMDV replication.
- The findings reveal a novel mechanism where HSP60 modulates viral replication through the regulation of mitophagy.
- HSP60 emerges as a potential therapeutic target for controlling FMDV infections.
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