The viral protein corona directs viral pathogenesis and amyloid aggregation

Nat Commun. 2019 May 27;10(1):2331. doi: 10.1038/s41467-019-10192-2.

Abstract

Artificial nanoparticles accumulate a protein corona layer in biological fluids, which significantly influences their bioactivity. As nanosized obligate intracellular parasites, viruses share many biophysical properties with artificial nanoparticles in extracellular environments and here we show that respiratory syncytial virus (RSV) and herpes simplex virus type 1 (HSV-1) accumulate a rich and distinctive protein corona in different biological fluids. Moreover, we show that corona pre-coating differentially affects viral infectivity and immune cell activation. In addition, we demonstrate that viruses bind amyloidogenic peptides in their corona and catalyze amyloid formation via surface-assisted heterogeneous nucleation. Importantly, we show that HSV-1 catalyzes the aggregation of the amyloid β-peptide (Aβ42), a major constituent of amyloid plaques in Alzheimer's disease, in vitro and in animal models. Our results highlight the viral protein corona as an acquired structural layer that is critical for viral-host interactions and illustrate a mechanistic convergence between viral and amyloid pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / immunology
  • Alzheimer Disease / pathology
  • Alzheimer Disease / virology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Bronchoalveolar Lavage Fluid / virology
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Female
  • Healthy Volunteers
  • Herpes Simplex / blood
  • Herpes Simplex / immunology
  • Herpes Simplex / pathology
  • Herpesvirus 1, Human / immunology
  • Herpesvirus 1, Human / pathogenicity*
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / metabolism*
  • Protein Aggregates / immunology
  • Protein Corona / immunology*
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus, Human / immunology
  • Respiratory Syncytial Virus, Human / pathogenicity*
  • Vero Cells

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Protein Aggregates
  • Protein Corona
  • amyloid beta-protein (1-42)