Rab4b is associated with inflammatory responses and TLR3-related signaling during Japanese encephalitis virus

Xinyun Du1, Qin Zhao2, Chang Miao1

  • 1Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.

Virology
|June 2, 2026
PubMed

Insights

Japanese Encephalitis Virus (JEV) infection triggers inflammation. This study reveals Ras-associated GTP-binding protein 4B (Rab4b) is crucial for JEV replication and inflammation by interacting with Toll-like receptor 3 (TLR3).

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Japanese Encephalitis Virus (JEV) is a mosquito-borne pathogen causing severe inflammation.
  • Ras-associated GTP-binding protein 4B (Rab4b) is known to mediate JEV entry into cells.
  • The exact role of Rab4b in JEV-induced inflammation is unclear.

Purpose of the Study:

  • To investigate the role of Rab4b in JEV replication and inflammatory responses.
  • To elucidate the molecular mechanism linking Rab4b to JEV-induced inflammation.

Main Methods:

  • Development of a Rab4b-knockout U251 cell model.
  • Measurement of viral replication and inflammatory mediator levels (IL-1β, IL-6, TNF-α, IFN-β).
  • Transcriptomic analysis and co-immunoprecipitation assays to identify molecular interactions.
  • Treatment with a Toll-like receptor 3 (TLR3) inhibitor.

Main Results:

  • Rab4b deficiency significantly inhibited JEV replication and reduced inflammatory mediator production.
  • Loss of Rab4b disrupted the Toll-like receptor 3 (TLR3)-related gene network.
  • Rab4b was found to interact with TLR3, and TLR3 inhibition mimicked the anti-inflammatory effects of Rab4b deficiency.

Conclusions:

  • Rab4b plays a critical role in promoting JEV replication and associated inflammation.
  • Rab4b is involved in a TLR3-dependent signaling pathway during JEV infection.
  • Further research is needed to fully understand the Rab4b-TLR3 interaction in JEV pathogenesis.

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