2. Academic Validation
  3. The viral protein corona directs viral pathogenesis and amyloid aggregation

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.
Kariem Ezzat 1 2,  Maria Pernemalm 3,  Sandra Pålsson 4,  Thomas C Roberts 5 6,  Peter Järver 4,  Aleksandra Dondalska 4,  Burcu Bestas 7 8,  Michal J Sobkowiak 9,  Bettina Levänen 10,  Magnus Sköld 11 12,  Elizabeth A Thompson 13,  Osama Saher 7 14,  Otto K Kari 15,  Tatu Lajunen 15,  Eva Sverremark Ekström 4,  Caroline Nilsson 16,  Yevheniia Ishchenko 17,  Tarja Malm 17,  Matthew J A Wood 5,  Ultan F Power 18,  Sergej Masich 19,  Anders Lindén 10 12,  Johan K Sandberg 9,  Janne Lehtiö 3,  Anna-Lena Spetz 20,  Samir El Andaloussi 7 5 21
Affiliations

Affiliations

  • 1 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, 10691, Sweden. [email protected].
  • 2 Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Stockholm, 14152, Sweden. [email protected].
  • 3 Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory and Karolinska Institutet, Stockholm, 17176, Sweden.
  • 4 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, 10691, Sweden.
  • 5 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX13PT, UK.
  • 6 Sanford Burnham Prebys Medical Discovery Institute, Development, Aging and Regeneration Program, La Jolla, CA, 92037, USA.
  • 7 Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Stockholm, 14152, Sweden.
  • 8 Discovery Sciences, R&D Biopharmaceuticals, AstraZeneca, Gothenburg, Sweden.
  • 9 Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, 14186, Sweden.
  • 10 Unit for Lung and Airway disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 17165, Sweden.
  • 11 Respiratory Medicine Unit, Department of Medicine, Karolinska Institutet, Stockholm, 17176, Sweden.
  • 12 Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, 17176, Sweden.
  • 13 Immunology and Allergy Unit, and Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, 17176, Sweden.
  • 14 Faculty of Pharmacy, Department of Pharmaceutics and Industrial Pharmacy, Cairo University, Cairo, 11562, Egypt.
  • 15 Drug Research Program, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, 00014, Finland.
  • 16 Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet and Sachs' Children and Youth Hospital, Stockholm, 11883, Sweden.
  • 17 A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, 70211, Finland.
  • 18 Centre of Experimental Medicine, Queens' University Belfast, Belfast, BT97BL, UK.
  • 19 Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 17177, Sweden.
  • 20 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, 10691, Sweden. [email protected].
  • 21 Evox Therapeutics Limited, Oxford Science Park, Oxford, OX44HG, UK.
PMID: 31133680 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.

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