The viral protein corona directs viral pathogenesis and amyloid aggregation

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 (Aβ 42 ), 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.

Contributions of DNA Damage to Alzheimer’s Disease

“…Herpes simplex virus-type 1 (HSV-1) infection is a well-recognized risk factor of AD [102,103]. HSV-1 induces AD via affecting multiple AD events, such as through enhancing Aβ 1−42 production [104]. The virus causes DSB accumulation in rat cortical neuron through downregulation of Ku80, an essential component of NHEJ ( Figure 2), and thus impairs NHEJ in cortical neurons [105].…”

Disentangling the Amyloid Pathways: A Mechanistic Approach to Etiology

“…(C) A schematic representation of HEN where an exogenous surface catalyze amyloid nucleation via binding, concentrating, and inducing conformational changes in the bound peptides/proteins, which facilitate amyloid transformation. (D) A negatively stained transmission electron microscopy picture demonstrating direct interaction between the surface of a virus (HSV-1) and a growing amyloid protofilament of Aβ 1-42 peptide (unpublished image from the viral catalyzed nucleation experiments performed in the study of Ezzat et al (2019), where HSV-1 was incubated with 50 µM Aβ 1-42 for 100 min. at 37 • C).…”

“…aggregation via HEN. This includes microbial surfaces (Bantle et al, 2019;Ezzat et al, 2019), lipid vesicles (Habchi et al, 2018), and nanoparticles (Linse et al, 2007). Additionally, polymer surfaces such as glycosaminoglycans (GAGs) (Iannuzzi et al, 2015) and nucleic acids (Liu and Zhang, 2011) have been shown to accelerate amyloid aggregation.…”

“…While non-protein factors have usually been considered "co-factors" to a "protein-only" driven process based on prion seeding (Soto, 2011), we emphasize that surfaces are independent causal factors as they are able to induce amyloid aggregation in the absence protein seeds/prions via the distinct and separate pathway of HEN. Lipid vesicles (Habchi et al, 2018), nanoparticles (Linse et al, 2007) and viruses (Ezzat et al, 2019) have been shown to induce amyloid aggregation via HEN in absence of preformed seeds. Additionally, being thermodynamically more favorable, HEN is more likely to be the prevalent pathway of amyloid aggregation in-vivo in the absence of genetic mutations that can facilitate HON.…”

2019 meeting of the global virus network

“…The authors also showed that HSV-1, which has been implicated in Alzheimer's disease, catalyzes the nucleation and accumulation of the Aβ42 peptide both in vitro and in vivo. Results from Ezzat et al, (2019) showed that unlike the viral genome coded surface proteins, the viral protein corona is an acquired structural layer that is dependent on the viral microenvironment resulting in different viral identities based on the target tissue and the target organism. Additionally, the viral coronadriven heterogeneous nucleation of amyloids illustrates convergence between viral and amyloid pathologies suggesting a direct physical mechanistic link that warrants further investigation.…”