Involvement of cyclophilin B in the replication of Japanese encephalitis virus

Hiroto Kambara1, Hideki Tani, Yoshio Mori

  • 1Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, Japan

Virology
|February 2, 2011
PubMed

Insights

Cyclosporin A inhibits Japanese encephalitis virus (JEV) by targeting CypB. This protein

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Japanese encephalitis virus (JEV), a Flaviviridae family member, causes significant neurological disease.
  • Understanding JEV replication mechanisms is crucial for developing antiviral strategies.

Purpose of the Study:

  • To investigate the effect of cyclosporin A (CsA) on JEV propagation.
  • To elucidate the role of cyclophilin B (CypB) in JEV replication.

Main Methods:

  • Cell-based assays using various mammalian cell lines.
  • Cyclosporin A treatment and CypB knockdown experiments.
  • Analysis of JEV propagation, viral protein interactions, and cyclophilin B peptidylprolyl cis-trans isomerase (PPIase) activity.

Main Results:

  • Cyclosporin A demonstrated potent anti-JEV activity by inhibiting CypB.
  • JEV propagation was significantly reduced in CypB-knockdown cells.
  • CypB's PPIase activity, not its mere presence, is essential for JEV replication, as indicated by rescue experiments with wild-type vs. PPIase-deficient CypB.
  • CypB interacts with JEV NS4A protein, suggesting a role in viral replication, not entry.

Conclusions:

  • CypB is a critical host factor for JEV replication.
  • The peptidylprolyl cis-trans isomerase (PPIase) activity of CypB is essential for JEV propagation.
  • CypB interacts with JEV NS4A, highlighting a potential therapeutic target for JEV infection.

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