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Regulation of Epstein-Barr Virus Minor Capsid Protein BORF1 by TRIM5α

Lih-Tsern Lin1, Yi-Shan Lu1, Hsiang-Hung Huang1

  • 1Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei City 106319, Taiwan.

International Journal of Molecular Sciences
|December 11, 2022
PubMed

Insights

The tripartite motif-containing protein 5 alpha (TRIM5α) targets Epstein-Barr virus (EBV) capsid protein BORF1 for degradation. This interaction destabilizes BORF1, revealing a new antiviral mechanism for TRIM5α against EBV.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Tripartite motif-containing protein 5 alpha (TRIM5α) is a known antiviral factor restricting retroviruses like human immunodeficiency virus (HIV).
  • TRIM5α also plays a role in innate immune signaling and mediates protein degradation through autophagosomes via TRIMsome formation.
  • Previous research demonstrated TRIM5α's role in Epstein-Barr virus (EBV) Rta ubiquitination and attenuation of viral lytic progression.

Purpose of the Study:

  • To investigate the interaction between TRIM5α and EBV capsid proteins.
  • To determine if TRIM5α induces the degradation of EBV capsid proteins.
  • To elucidate the mechanism by which TRIM5α affects EBV capsid protein stability.

Main Methods:

  • Glutathione S-transferase (GST) pulldown assays to identify interacting proteins.
  • Immunoprecipitation assays to confirm protein interactions.
  • Site-directed mutagenesis to analyze binding domains and ubiquitination sites.
  • Western blotting to assess protein stability in the presence of TRIM5α and chloroquine.

Main Results:

  • TRIM5α directly binds to BORF1, an EBV capsid protein essential for nuclear transport and capsid assembly.
  • TRIM5α promotes the ubiquitination of BORF1, dependent on the PRY/SPRY domain of TRIM5α.
  • TRIM5α expression reduces the stability of a BORF1 mutant lacking lysine residues (BORF1(6KR)).
  • Autophagic degradation is implicated as chloroquine treatment restores BORF1(6KR) stability, suggesting TRIM5α targets BORF1 for autophagic clearance.

Conclusions:

  • TRIM5α interacts with and induces the autophagic degradation of the EBV capsid protein BORF1.
  • This study expands the known antiviral functions of TRIM5α beyond retroviruses to include herpesviruses like EBV.
  • The findings reveal a novel mechanism of TRIM5α-mediated restriction against EBV infection by targeting essential capsid components.
Keywords:
BORF1Epstein-Barr virusTRIM5αTRIMosomeautophagyhost-viral interactioninnate immunityubiquitination

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