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

## TL;DR

This study shows that the SIRT1-p53 pathway helps the MVC virus replicate by reducing cell death and controlling the cell cycle in infected cells.

## Contribution

The study identifies SIRT1 as a key host factor supporting MVC replication through its regulation of p53 and cell cycle arrest.

## Key findings

- MVC infection increases SIRT1 expression and activates the SIRT1-p53 signaling axis.
- Pharmacological SIRT1 activation promotes MVC replication and reduces apoptosis in infected cells.
- SIRT1 knockdown accelerates apoptosis and reduces S-phase arrest during MVC infection.

## Abstract

Minute virus of canines (MVC) is an autonomous canine parvovirus that causes severe pathological outcomes, including embryo mortality, spontaneous abortion, and congenital malformations in neonatal puppies. Although MVC infection has been shown to induce host cell cycle arrest and apoptosis, the underlying regulatory mechanisms that coordinate cell proliferation and control apoptotic responses during viral replication remain poorly understood. Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase that plays a critical role in regulating cell cycle progression, DNA damage responses, and apoptosis. However, its involvement in MVC infection has not been fully elucidated. Herein, we show that MVC infection markedly upregulates the mRNA and protein expression levels of SIRT1 in a time-dependent manner. MVC infection activates the SIRT1-p53 signaling axis and modulates the acetylation status of p53. In addition, MVC alters the subcellular distribution of SIRT1, promoting its nuclear translocation and colocalization with the viral protein VP2. Functional analyses demonstrated that pharmacological activation of SIRT1 enhanced the viability of MVC-infected WRD cells (virus-tropic cell), promoting viral replication, prolonging S-phase arrest, and reducing apoptosis. Conversely, inhibition of SIRT1 produced the opposite effects, which were closely associated with regulation of the SIRT1-p53 signaling axis. Moreover, SIRT1 knockdown accelerated apoptosis and attenuated S-phase arrest, whereas SIRT1 overexpression further strengthened S-phase retention. Collectively, our findings identify the SIRT1-p53 signaling axis as an important regulator of cell cycle progression and apoptosis during MVC infection, highlighting SIRT1 as a key host factor that supports viral replication and persistence and a potential target for antiviral intervention.