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 Otto K. Kari
A1 Tatu Lajunen
A1 Yevheniia Ishchenko
A1 Tarja Malm
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/2018/09/10/246785.abstract
AB Nanoparticles accumulate a layer of host factors on their surface (protein corona) in biological fluids, which influences the nanoparticle activity. We hypothesized that viruses also constitute nanoparticles in this respect and we provide evidence for the existence of a viral protein corona that has 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 rich and distinctive protein corona in different biological fluids 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 biological fluid. Furthermore, we demonstrate that 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) possesses a protein corona and catalyzes the amyloid aggregation of the amyloid-beta (Aβ42) peptide which is the major constituent of amyloid plaques in Alzheimer’s disease (AD). We also show that HSV-1 infection accelerates Aβ42 aggregation in the hippocampi of a mouse model of AD. 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 corona-driven amyloid catalysis illustrates convergence between viral and amyloid pathologies in the extracellular environment suggesting a novel mechanistic link that warrants further investigation.