The SIRT1-Mediated p53 Deacetylation Pathway Modulates Apoptosis and Promotes Viral Replication in MVC-Infected Cells

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Minute virus of canines (MVC) causes severe reproductive issues in puppies.
• MVC infection induces cell cycle arrest and apoptosis, but regulatory mechanisms are unclear.
• Sirtuin 1 (SIRT1) is a key regulator of cell cycle and apoptosis, yet its role in MVC infection is unknown.

Purpose of the Study:

• To investigate the role of Sirtuin 1 (SIRT1) in Minute virus of canines (MVC) infection.
• To elucidate the regulatory mechanisms of cell cycle progression and apoptosis during MVC infection.

Main Methods:

• Assessed SIRT1 expression levels in MVC-infected cells.
• Analyzed the SIRT1-p53 signaling axis and p53 acetylation.
• Investigated SIRT1's subcellular localization and its interaction with viral protein VP2.
• Utilized pharmacological activators/inhibitors and knockdown/overexpression of SIRT1 to study its functional impact on MVC-infected cells.

Main Results:

• MVC infection significantly upregulated SIRT1 expression in a time-dependent manner.
• MVC infection activated the SIRT1-p53 axis, altering p53 acetylation and promoting SIRT1 nuclear translocation.
• SIRT1 activation enhanced viral replication, prolonged S-phase arrest, and reduced apoptosis in infected cells.
• SIRT1 inhibition or knockdown led to increased apoptosis and attenuated S-phase arrest.

Conclusions:

• The SIRT1-p53 signaling axis is a critical regulator of cell cycle and apoptosis during MVC infection.
• SIRT1 acts as a host factor supporting MVC replication and persistence.
• SIRT1 represents a potential therapeutic target for antiviral interventions against MVC.