Retroviral foamy virus gag induces parkin-dependent mitophagy

Shanshan Wang1, Tongtong Du1, Jun Yan2

  • 1Hubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China.

Retrovirology
|May 2, 2025
PubMed
Abstract

Insights

Prototype foamy virus (PFV) infection triggers mitophagy, a process where cells degrade damaged mitochondria. The viral Gag protein is key, activating the PINK1-Parkin pathway and upregulating Rab5a to promote this process.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Prototype foamy virus (PFV) establishes lifelong latent infections.
  • Mechanisms of PFV latent infection are not fully understood.
  • PFV is known to promote autophagy, but its role in mitophagy is unclear.

Purpose of the Study:

  • To investigate whether PFV infection induces mitophagy.
  • To identify viral factors responsible for mitophagy induction.
  • To elucidate the molecular pathways involved in PFV-induced mitophagy.

Main Methods:

  • Assessing mitochondrial damage and reactive oxygen species (ROS) production post-PFV infection.
  • Evaluating the role of PFV Gag protein in mitophagy.
  • Investigating the involvement of the PINK1-Parkin pathway and Rab5a.
  • Utilizing gene overexpression and knockdown techniques.

Main Results:

  • PFV infection causes time-dependent mitochondrial damage and increases mitochondrial ROS (mtROS).
  • PFV Gag protein is essential for triggering mitophagy, causing mitochondrial damage and mitophagy in a dose-dependent manner.
  • Gag activates the PINK1-Parkin pathway, and Parkin knockdown inhibits Gag-induced mitophagy.
  • Rab5a is upregulated by Gag, and its inhibition reverses Gag-induced mitophagy.

Conclusions:

  • PFV infection induces mitophagy, a process mediated by the viral Gag protein.
  • Gag induces Parkin-dependent mitophagy, involving the upregulation of Rab5a.
  • Findings provide insights into PFV infection mechanisms and virus-host interactions.

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