EV71 Infection Induces IFNβ Expression in Neural Cells.

Hsing-I Huang,Sheng-Hung Chen,Jhao-Yin Lin

doi:10.3390/v11121121

Hsing-I Huang, Sheng-Hung Chen + Show 1 more

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https://doi.org/10.3390/v11121121

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Journal: Viruses	Publication Date: Dec 4, 2019
Citations: 19	License type: CC BY 4.0

Affiliation: Chang Gung University, Chang Gung Memorial Hospital

Abstract

Enterovirus 71 (EV71) can invade the central nervous system (CNS) and cause neurological disease. Accumulating evidence indicates that EV71 can directly infect neurons in the CNS. Innate immune responses in the CNS have been known to play an essential role in limiting pathogen infections. Thus, investigating the effects of EV71 infection of neural cells is important for understanding disease pathogenesis. In this study, human neural cells were infected with EV71, and interferonβ (IFNβ) expression was examined. Our results show that IFNβ expression was upregulated in EV71-infected neural cells via pattern recognition receptors (PRRs) sensing of virus RNA. The PRRs Toll-like receptor 3 (TLR3), Toll-like receptor 8 (TLR8), and melanoma differentiation-associated gene-5 (MDA-5), but not retinoic acid-inducible gene-I (RIG-I) and Toll-like receptor 7 (TLR7), were found to be EV71-mediated IFNβ induction. Although viral proteins exhibited the ability to cleave mitochondrial antiviral signaling protein (MAVS) and Toll/IL-1 receptor (TIR) domain-containing adaptor-inducing IFN-β (TRIF) in neural cells, levels of viral protein expression were low in these cells. Furthermore, neural cells efficiently produced IFNβ transcripts upon EV71 vRNA stimulation. Treating infected cells with anti-IFNβ antibodies resulted in increased virus replication, indicating that IFNβ release may play a role in limiting viral growth. These results indicate that EV71 infection can induce IFNβ expression in neural cells through PRR pathways.

Highlights

Enterovirus 71 (EV71) is a member of the family Picornaviridae, which is composed of non-enveloped single-stranded RNA viruses
Our results demonstrate that EV71 can induce IFNβ expression in neural cells and that this increased IFNβ expression is associated with Toll-like receptor 3 (TLR3), Toll-like receptor 8 (TLR8), and MDA5
To examine whether EV71 infection was sufficient to induce IFNβ expression in neural cells, human glioblastoma cell line (SF268) and neuroblastoma cell lines (IMR32 and SH-SY5Y) were cultured and infected with EV71 at a multiplicity of infection (MOI) of 40, and the infected cells were harvested at different time points

Summary

Introduction

Enterovirus 71 (EV71) is a member of the family Picornaviridae, which is composed of non-enveloped single-stranded RNA viruses. EV71 has been recognized for its ability to invade the central nervous system (CNS) and cause neurological symptoms. Data from clinical and animal studies suggest that after infection EV71 viral capsid proteins are present in neural cells in the brain, providing evidence that EV71 can directly infect neurons [1,2]. In the brains of EV71-infected monkeys, EV71 antigen could be detected in the thalamus and motor cortex [1]. EV71 RNA and protein expression could be detected in the brain neurons from deceased EV71-infected patients [2]. The effects of EV71 infection in host neural cells remain to be identified

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