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Role of Poly(A)-Binding Protein Cytoplasmic 1, a tRNA-Derived RNA Fragment-Bound Protein, in Respiratory Syncytial

Devin V Davis1, Eun-Jin Choi1, Deena Ismail1

  • 1Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.

Pathogens (Basel, Switzerland)
|September 28, 2024
PubMed

Insights

Respiratory Syncytial Virus (RSV) infection induces tRNA fragments (tRFs) that promote viral replication by interacting with host proteins like PABPC1. Suppressing PABPC1 impacts RSV assembly and host cytokine production.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Respiratory Syncytial Virus (RSV) causes significant lower respiratory tract infections (LRTI), particularly in vulnerable populations.
  • While new vaccines and treatments exist, limited accessibility and variable treatment responses necessitate further research into host-RSV interactions.
  • tRNA-derived RNA fragments (tRFs) are emerging as key regulators in viral infections, with our previous work showing RSV induces tRFs to enhance viral replication.

Purpose of the Study:

  • To investigate the role of host proteins interacting with RSV-induced tRFs in regulating viral replication.
  • To identify specific tRFs and their protein partners involved in the host-RSV interaction.
  • To elucidate the mechanism by which tRFs and their associated proteins modulate viral assembly and host immune response.

Main Methods:

  • Proteomics analysis to identify proteins associated with RSV-induced tRFs, specifically tRF5-GluCTC.
  • Western blot and co-immunoprecipitation to confirm the interaction between tRF5-GluCTC and poly(A)-binding protein cytoplasmic 1 (PABPC1).
  • siRNA-mediated knockdown of PABPC1 to assess its impact on RSV replication, viral assembly, and host cytokine production (MIP-1α, MIP-1β, MCP-1, TNF-α).

Main Results:

  • Proteomics identified PABPC1 as a protein associated with the RSV-induced tRF5-GluCTC.
  • Experimental validation confirmed the complex formation between tRF5-GluCTC and PABPC1.
  • PABPC1 knockdown increased RSV genome copies but reduced infectious progeny, indicating a role in viral assembly via interaction with the RSV matrix protein.
  • PABPC1 suppression led to decreased production of key inflammatory cytokines.

Conclusions:

  • RSV-induced tRFs can regulate viral replication not only by targeting mRNAs but also through their bound proteins.
  • PABPC1 plays a crucial role in RSV assembly and infectious virus production.
  • tRF-protein interactions represent a novel mechanism for regulating viral infections and host immune responses.

Keywords:
PABPC1RSVtRFviral gene transcription and viral genome replication

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