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The prion-family protein Doppel exerts a protective role during influenza virus infection

Soraya Dinant1, Johan Castille2, Charlotte Deloizy1

  • 1UMR892 VIM, UVSQ, INRAE, Université Paris-Saclay, Jouy-en-Josas, F78352, France.

Journal of Immunology (Baltimore, Md. : 1950)
|April 9, 2025
PubMed

Insights

Doppel (Prnd-/-) protein deficiency increases susceptibility to influenza A virus by promoting excessive neutrophil influx in mice lungs. This highlights Doppel's role in regulating immune responses and disease outcomes.

Area of Science:

  • Immunology
  • Virology
  • Neuroscience

Background:

  • The cellular prion protein (PrPC) protects against viral infections.
  • Prion family members Shadoo and Doppel's roles in influenza A virus infection are unexplored.

Purpose of the Study:

  • To investigate the role of Shadoo and Doppel in protection against influenza A virus in mice.
  • To understand the immune mechanisms underlying Doppel's effect on influenza A virus infection.

Main Methods:

  • Gene knockout mice (Prnp-/-, Prnd-/-, Sprn-/-) were infected with influenza A virus.
  • Lung gene expression, viral replication, histology, transcriptomics, and bronchoalveolar lavage were analyzed.
  • Neutrophil depletion experiments were performed.

Main Results:

  • Prnd-/- mice exhibited increased susceptibility and morbidity compared to wild-type mice.
  • Doppel deficiency did not enhance viral replication but led to significant neutrophil influx and inflammation.
  • Neutrophil depletion mitigated pathology in Prnd-/- mice, partially restoring a wild-type phenotype.

Conclusions:

  • Doppel plays a complex role in modulating the host immune response to influenza A virus.
  • Excessive neutrophil recruitment, driven by Doppel deficiency, contributes to increased disease severity.
  • Targeting neutrophil activity may be a therapeutic strategy for influenza A virus infection in the context of Doppel deficiency.
Keywords:
Doppelinfluenza virusprion family protein

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