# Retroviral foamy virus gag induces parkin-dependent mitophagy

## TL;DR

This study shows that the PFV Gag protein causes mitochondrial damage and mitophagy, which may explain how the virus maintains a latent infection.

## Contribution

The study identifies PFV Gag as a key inducer of Parkin-dependent mitophagy through Rab5a upregulation.

## Key findings

- PFV infection damages mitochondria and increases mtROS, leading to mitophagy.
- PFV Gag activates the PINK1-Parkin pathway and upregulates Rab5a to induce mitophagy.
- Knockdown of Parkin or inhibition of Rab5a inhibits Gag-induced mitophagy.

## Abstract

Prototype foamy virus (PFV) is a complex retrovirus that can maintain latent infection for life after viral infection of the host. However, the mechanism of latent infection with PFV remains unclear. Our previous studies have shown that PFV promotes autophagy flux, but whether PFV causes mitophagy remains unclear.

In this study, we demonstrated that PFV infection damages mitochondria, increases mitochondria reactive oxygen species (mtROS) production, and induces mitophagy in a time-dependent manner. Further investigation revealed that PFV Gag is a crucial protein responsible for triggering mitophagy. The overexpression of Gag leads to mitochondrial damage and stimulates mitophagy in a dose-dependent manner. Additionally, overexpression of Gag activates the PINK1-Parkin signaling pathway, while the knockdown of Parkin inhibits Gag-induced mitophagy. Furthermore, Rab5a was significantly upregulated in cells overexpressed Gag, and the inhibition of Rab5a reversed the effects of Gag-induced mitophagy.

Our data suggested that PFV can induce mitophagy and Gag induces Parkin-dependent mitophagy by upregulating Rab5a. These findings not only enhance a better understanding of the foamy virus infection mechanisms but also provide critical insights into novel virus-host cell interactions.

The online version contains supplementary material available at 10.1186/s12977-025-00664-3.