A novel protein encoded by circVPS13D attenuates antiviral innate immunity by targeting MAVS in teleost fish

Linchao Wang1, Yanhong Song1, Xiaolong Yan1

  • 1Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University , Shanghai, China.

Journal of Virology
|October 16, 2023
PubMed
Abstract

Insights

Circular RNA circVPS13D promotes viral replication and suppresses fish antiviral immunity by inhibiting the RLR signaling pathway. This study identifies circVPS13D as a key regulator in teleost fish antiviral defense.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in gene regulation.
  • The involvement of protein-coding circRNAs in antiviral immunity is an emerging area of research.
  • Understanding circRNA functions is crucial for developing novel antiviral strategies.

Purpose of the Study:

  • To investigate the role of circVPS13D in the antiviral immune response of teleost fish.
  • To elucidate the mechanism by which circVPS13D affects viral replication and immune signaling.
  • To identify circVPS13D as a potential target for enhancing fish antiviral immunity.

Main Methods:

  • Quantitative real-time PCR to measure circVPS13D expression.
  • Viral challenge experiments to assess the impact of circVPS13D on viral replication.
  • Western blotting and luciferase assays to investigate signaling pathway activation.
  • RNA interference and plasmid transfection to manipulate circVPS13D levels.

Main Results:

  • circVPS13D expression was upregulated during SCRV infection.
  • circVPS13D expression promoted SCRV replication and inhibited fish antiviral responses.
  • circVPS13D, via its encoded protein VPS13D-170aa, targeted MAVS to inhibit the RLRs antiviral signaling pathway.
  • VPS13D-170aa was confirmed as a negative regulator of antiviral immunity.

Conclusions:

  • circVPS13D plays a significant role in regulating the antiviral immune response in teleost fish.
  • The protein-coding circRNA circVPS13D acts as a negative regulator by inhibiting the RLRs signaling pathway.
  • VPS13D-170aa is a key effector molecule of circVPS13D in modulating antiviral immunity, offering potential therapeutic targets.

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