RT Journal Article SR Electronic T1 The Viral protein Corona Directs Viral Pathogenesis and Amyloid Aggregation JF bioRxiv FD Cold Spring Harbor Laboratory SP 246785 DO 10.1101/246785 A1 Kariem Ezzat A1 Maria Pernemalm A1 Sandra Pålsson A1 Thomas C. Roberts A1 Peter Järver A1 Aleksandra Dondalska A1 Burcu Bestas A1 Michal J. Sobkowiak A1 Bettina Levänen A1 Magnus Sköld A1 Elizabeth A. Thompson A1 Matthew J.A. Wood A1 Ultan F. Power A1 Sergej Masich A1 Anders Lindén A1 Johan K. Sandberg A1 Janne Lehtiö A1 Anna-Lena Spetz A1 Samir EL Andaloussi YR 2018 UL http://biorxiv.org/content/early/2018/01/16/246785.abstract 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.