PT  - JOURNAL ARTICLE
AU  - Kariem Ezzat
AU  - Maria Pernemalm
AU  - Sandra Pålsson
AU  - Thomas C. Roberts
AU  - Peter Järver
AU  - Aleksandra Dondalska
AU  - Burcu Bestas
AU  - Michal J. Sobkowiak
AU  - Bettina Levänen
AU  - Magnus Sköld
AU  - Elizabeth A. Thompson
AU  - Matthew J.A. Wood
AU  - Ultan F. Power
AU  - Sergej Masich
AU  - Anders Lindén
AU  - Johan K. Sandberg
AU  - Janne Lehtiö
AU  - Anna-Lena Spetz
AU  - Samir EL Andaloussi
TI  - The Viral protein Corona Directs Viral Pathogenesis and Amyloid Aggregation
AID  - 10.1101/246785
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 246785
4099  - http://biorxiv.org/content/early/2018/01/16/246785.short
4100  - http://biorxiv.org/content/early/2018/01/16/246785.full
AB  - Nanoparticles accumulate a plethora of host factors on their surface (protein corona) in biological fluids, which influence the nanoparticle activity. Here we provide evidence for the existence of a rich viral protein corona and show its implications for viral infectivity, immune cell activation and catalysis of amyloid aggregation. We demonstrate that respiratory syncytial virus (RSV), a major cause of respiratory tract infections, accumulates a distinctive protein corona in different biofluids including: human plasma, human bronchoalveolar lavage fluid, non-human primate plasma and fetal bovine serum. Additionally, corona pre-coating differentially affects viral infectivity and its ability to activate human monocyte-derived dendritic cells (moDCs) depending on the biofluid. Furthermore, we demonstrate that cell-free RSV can bind and catalyze the amyloid aggregation of an amyloidogenic peptide derived from the islet amyloid polypeptide (IAPP) via surface-assisted nucleation. Similarly, we show that herpes simplex virus 1 (HSV-1) catalyzes the amyloid aggregation of the amyloid-beta (Aβ42) peptide which is the major constituent of amyloid plaques in Alzheimer’s disease. Our results provide a proof-of-concept for the presence of a viral protein corona layer that is dependent on the microenvironment and influences viral-host interactions. Additionally, the demonstration of viral nanosurface driven amyloid catalysis in an extracellular environment illustrates convergence between viral and amyloid pathologies suggesting a novel mechanistic link that warrants further investigation.Significance Outside cells, viruses are biophysically equivalent to synthetic nanoparticles as they rely on intracellular machinery for replication. Here we show that similar to nanoparticles, viruses accumulate a rich and unique layer of host factors in different biological fluids (viral protein corona) which influences infectivity and immune cell activation. We also show that viruses can act as nanosurface catalysts for the aggregation of amyloid peptides such as amyloid beta which is involved in Alzheimer’s disease. Our results highlight the important role of viral extracellular interactions in viral pathogenicity and demonstrate a novel link between viral and protein aggregation diseases.