Common carp USP30s restrict SVCV replication by attenuating mitophagy

Chen Li1, Songjie Qi1, Mengxi Zhang1

  • 1Engineering Lab of Henan Province for Aquatic Animal Disease Control, College of Fisheries, Henan Normal University, Xinxiang, 453007, China.

Insights

Common carp USP30 proteins (CcUSP30s) counteract excessive mitophagy during viral infection. This study reveals CcUSP30s preserve mitochondrial integrity, limiting viral replication and offering potential aquaculture strategies.

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Mitophagy, a selective autophagic process, is crucial for antiviral immunity by clearing damaged mitochondria.
  • The deubiquitinating enzyme USP30 regulates mitophagy in mammals, but its role in teleost antiviral defense is unknown.

Purpose of the Study:

  • To investigate the function of USP30 homologs (CcUSP30-A and CcUSP30-B) in common carp (Cyprinus carpio) antiviral immunity.
  • To determine the role of CcUSP30s in regulating mitophagy during spring viremia of carp virus (SVCV) infection.

Main Methods:

  • Identification and characterization of CcUSP30-A and CcUSP30-B in common carp.
  • In vitro analysis of SVCV infection, mitophagy induction (PINK1-Parkin pathway), and CcUSP30s' effects on viral replication.
  • Overexpression studies of CcUSP30-A and CcUSP30-B to assess their impact on mitochondrial proteins, mitophagy, and SVCV replication.

Main Results:

  • SVCV infection induced PINK1-Parkin-dependent mitophagy, which the virus exploited for replication.
  • Overexpression of CcUSP30-A and CcUSP30-B increased mitochondrial protein levels, reduced SVCV-induced mitophagy, and inhibited viral replication.
  • CcUSP30-B exhibited stronger anti-mitophagy and anti-viral activities compared to CcUSP30-A.

Conclusions:

  • CcUSP30s antagonize the PINK1-Parkin pathway, mitigating excessive mitophagy and limiting SVCV replication.
  • USP30 acts as an antiviral regulator in teleosts by maintaining mitochondrial integrity.
  • CcUSP30s represent potential therapeutic targets for controlling SVCV in aquaculture.

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