Phosphatidylserine-exposing extracellular vesicles in body fluids are an innate defence against apoptotic mimicry

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Rüdiger Groß1, Hanna Reßin1, Pascal von Maltitz1

  • 1Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.

Nature Microbiology
|March 26, 2024
PubMed

Insights

Extracellular vesicles (EVs) in body fluids inhibit viruses like Dengue and Ebola by exposing phosphatidylserine (PS). This PS prevents viruses using apoptotic mimicry from attaching and entering cells, limiting their spread.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Some viruses are rarely transmitted sexually or orally despite presence in bodily fluids.
  • Extracellular vesicles (EVs) in saliva and semen were previously found to inhibit Zika virus.
  • The antiviral spectrum and mechanism of EVs remained unclear.

Purpose of the Study:

  • To investigate the antiviral spectrum of EVs in body fluids.
  • To elucidate the mechanism by which EVs inhibit viral infections.
  • To understand the role of EVs in innate defense against viral transmission.

Main Methods:

  • Lipidomics and flow cytometry were used to analyze EVs.
  • In vitro assays were performed using physiological concentrations of EVs.
  • Viral entry inhibition was assessed for various viruses.

Main Results:

  • EVs in body fluids expose phosphatidylserine (PS).
  • PS on EVs blocks viruses that use apoptotic mimicry (e.g., Dengue, Ebola, Zika) by interfering with attachment and entry.
  • EVs did not inhibit viruses using different entry receptors (e.g., SARS-CoV-2, HIV-1).

Conclusions:

  • PS-rich EVs in body fluids provide innate defense against viruses employing apoptotic mimicry.
  • This mechanism explains limited sexual/oral transmission of certain viruses, favoring blood or arthropod transmission routes.
  • EVs represent a crucial component of the innate immune system against specific viral pathogens.

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