Role of Microglia in Oxidative Toxicity Associated with Encephalomycarditis Virus Infection in the Central Nervous System

Yasuhisa Ano,Takashi Onodera,Akikazu Sakudo

doi:10.3390/ijms13067365

Abstract

The single-stranded RNA encephalomyocarditis virus (EMCV) can replicate in the central nervous system (CNS) and lead to prominent brain lesions in the stratum pyramidale hippocampus and the stratum granulosum cerebelli. Activated microglia cells infected by EMCV produce a massive burst of reactive oxygen species (ROS) via NADPH oxidase 2 (NOX2) activation, leading to neuronal death. Balancing this effect is mechanisms by which ROS are eliminated from the CNS. Cellular prion protein (PrPC) plays an important antioxidant role and contributes to cellular defense against EMCV infection. This review introduces recent knowledge on brain injury induced by EMCV infection via ROS generation as well as the involvement of various mediators and regulators in the pathogenesis.

Highlights

In the central nervous system (CNS), reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are generated as toxic byproducts in metabolic processes
NADPH oxidases (NOX) have cell-specific distributions and play a role in many redox-sensitive physiological functions, including host defense, inflammation, cellular signaling, and cell growth [36]. It has been known since the discovery of the first member of the family, NADPH oxidase 2 (NOX2), that the NOXs play a role in the innate immune response to infections
This study investigated the antioxidant effect of coenzyme Q10 (CoQ10) against oxidative injury and DNA damage in mice infected with encephalomyocarditis virus (EMCV) by the intraperitoneal route

Summary

Introduction

In the central nervous system (CNS), reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are generated as toxic byproducts in metabolic processes. Overproduction of ROS due to exaggerated innate immune responses can be toxic to host cells such as neurons in the CNS [3,4]. It is recently reported that the excessive ROS produced in microglia by EMCV-B infection are severely toxic for neuronal cells in mouse brains [7]. Microglial cells are activated in response to cerebral ischemia, infection, and neurodegenerative diseases and form the bulk of the response to endotoxin lipopolysaccharides (LPS) in the central nervous system (CNS) [9,10]. Microglia are activated by viral infection of the CNS and generate massive amounts of cytotoxic ROS via NOX2, which in turn induce neuronal apoptosis. This review focuses on the role of innate immunity against EMCV infection and the mechanisms of ROS-mediated cytotoxicity in CNS neurons under conditions of EMCV infection

Encephalomycarditis Virus

Innate Immunity in EMCV Virus Infection

Microglia Activation by Virus Infection in the CNS

Conclusions