Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication.

Gefei Wang,Zhiwu Jiang,Jianping Dai,Rui Li,Liming Gu,Yanxia Chen,Kangsheng Li

doi:10.1155/2016/8076989

Gefei Wang, Zhiwu Jiang + Show 5 more

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https://doi.org/10.1155/2016/8076989

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Abstract

Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i.) but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

Highlights

Influenza virus is an enveloped, multiple-segmented, negative-stranded RNA virus that mainly infects the respiratory tract and causes health problems ranging from common cold-like symptoms to severe infections such as pneumonia
Microglia belong to resident phagocytic cells which function as the first line of central nervous system (CNS) defense, and astrocytes are the principal source of cytokines secretion upon stress, injury, and infection
The potential routes for influenza A virus spreading into CNS are hematogenous spread or neural spread, which is related to the subtype of influenza A virus [19, 20]

Summary

Introduction

Influenza virus is an enveloped, multiple-segmented, negative-stranded RNA virus that mainly infects the respiratory tract and causes health problems ranging from common cold-like symptoms to severe infections such as pneumonia. Influenza virus is associated with many neurological complications such as encephalopathy/encephalitis syndrome, Reye’s syndrome, hemorrhagic shock, encephalopathy syndrome, and acute necrotizing encephalopathy [1,2,3]. The microenvironment of central nervous system (CNS) is highly specialized and is considered an immune-privileged site due to the CNS-driven passive interactions with the immune system [4, 5]. These mechanisms involve neuron and glial cells including microglia, astrocytes, and oligodendrocytes [5]. Recent researches have demonstrated that neurons might host and regulate innate and adaptive immune responses to counter viral infection in the CNS [8,9,10]

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