Gold Nanoparticles Crossing Blood-Brain Barrier Prevent HSV-1 Infection and Reduce Herpes Associated Amyloid-βsecretion.

Rodriguez-Izquierdo I,Serramia Mj,Bullido Mj,De La Mata Fj,Muñoz-Fernández Ma,Gomez R

doi:10.3390/jcm9010155

Abstract

Infections caused by HSV-1 and their typical outbreaks invading the nervous system have been related to neurodegenerative diseases. HSV-1 infection may deregulate the balance between the amyloidogenic and non-amyloidogenic pathways, raising the accumulation of amyloid-β peptides, one of the hallmarks in the neurodegenerative diseases. An effective treatment against both, HSV-1 infections and neurodegeneration, is a major therapeutic target. Therefore, gold nanoparticles (NPAus) have been previously studied in immunotherapy, cancer and cellular disruptions with very promising results. Our study demonstrates that a new NPAus family inhibits the HSV-1 infection in a neural-derived SK-N-MC cell line model and that this new NPAus reduces the HSV-1-induced β-secretase activity, as well as amyloid-β accumulation in SK-APP-D1 modifies cell line. We demonstrated that NPAuG3-S8 crosses the blood-brain barrier (BBB) and does not generate cerebral damage to in vivo CD1 mice model. The NPAuG3-S8 could be a promising treatment against neuronal HSV-1 infections and neuronal disorders related to the Aβ peptides.

Highlights

Herpes Simplex Virus (HSV) type 1 is one of the most common infections in the human population nowadays [1]
Our study reveals the biosafety of three gold NPs in SK-N-MC neural-derived cell lines
NPAuG2-S4 and NPAuG3-S8 are capable to inhibit the HSV-1 infection in neuronal cell lines, both in pre-treatment and treatment assays, rising the more significant inhibition rates in the treatment assays. We showed that both NPAuG2-S4 and NPAuG3-S8 inhibit HSV-1 bycellular protection against the infection in SK-N-MC, and that NPAuG3-S8 has a dual behavior, acting against the virus as well as protecting the target cell against HSV-1 infection (Graphical Abstract)

Summary

Introduction

Herpes Simplex Virus (HSV) type 1 is one of the most common infections in the human population nowadays [1]. More than 65% of the human population up to 50 years is infected by HSV-1. This virus establishes lifelong latent infections within the nervous system [2], avoiding the immune system mechanisms and raising the subsequent recurrent episodes [3]. The herpes simplex virus encephalitis (HSE) can result from primary infection as well as for recurrent HSV-1 episodes, HSV-1 impacts especially in immunocompromised patients, increasing the risk of developing HSE [4]. As familial AD (FAD), AD is caused by mutations in three genes which codify the amyloid precursor protein (APP) [14], whereas sporadic AD (SAD) is linked to several genetic and environmental risk factors, consistently related to neural infections such as those caused by HSV-1 [11,12,13,15,16]

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