Interactions of human microglia cells with Japanese encephalitis virus

Nils Lannes,Artur Summerfield,Luis Filgueira,Brigitte Scolari,Michael Walch,Viviane Neuhaus,Solange Kharoubi-Hess

doi:10.1186/s12985-016-0675-3

Nils Lannes, Artur Summerfield + Show 5 more

Open Access

https://doi.org/10.1186/s12985-016-0675-3

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Journal: Virology journal	Publication Date: Jan 14, 2017
Citations: 35	License type: open-access

Affiliation: University of Fribourg, University of Bern

Abstract

BackgroundJapanese encephalitis virus (JEV) is a neurotropic flavivirus causing mortality and morbidity in humans. Severe Japanese encephalitis cases display strong inflammatory responses in the central nervous system and an accumulation of viral particles in specific brain regions. Microglia cells are the unique brain-resident immune cell population with potent migratory functions and have been proposed to act as a viral reservoir for JEV. Animal models suggest that the targeting of microglia by JEV is partially responsible for inflammatory reactions in the brain. Nevertheless, the interactions between human microglia and JEV are poorly documented.MethodsUsing human primary microglia and a new model of human blood monocyte-derived microglia, the present study explores the interaction between human microglia and JEV as well as the role of these cells in viral transmission to susceptible cells. To achieve this work, vaccine-containing inactivated JEV and two live JEV strains were applied on human microglia.ResultsLive JEV was non-cytopathogenic to human microglia but increased levels of CCL2, CXCL9 and CXCL10 in such cultures. Furthermore, human microglia up-regulated the expression of the fraktalkine receptor CX3CR1 upon exposure to both JEV vaccine and live JEV. Although JEV vaccine enhanced MHC class II on all microglia, live JEV enhanced MHC class II mainly on CX3CR1+ microglia cells. Importantly, human microglia supported JEV replication, but infectivity was only transmitted to neighbouring cells in a contact-dependent manner.ConclusionOur findings suggest that human microglia may be a source of neuronal infection and sustain JEV brain pathogenesis.

Highlights

Japanese encephalitis virus (JEV) is a neurotropic flavivirus causing mortality and morbidity in humans
JEV is not cytopathogenic to human microglia A study using mouse microglia suggest that those cells are a possible viral reservoir and contribute substantially to JEV pathogenesis [17]
In order to investigate the interactions between microglia in humans and JEV, changes in the morphology of the cells were explored using bright field microscopy and flow cytometry

Summary

Introduction

Japanese encephalitis virus (JEV) is a neurotropic flavivirus causing mortality and morbidity in humans. Severe Japanese encephalitis cases display strong inflammatory responses in the central nervous system and an accumulation of viral particles in specific brain regions. Japanese encephalitis (JE) is an acute inflammatory disease of the central nervous system (CNS) caused by the neurotropic flavivirus JE virus (JEV). JEV is transmitted by mosquito vectors via a zoonotic cycle involving pigs as amplifying and water birds as reservoir host, the latter do not typically develop illness upon JEV infection [2]. Competent vectors for JEV have been recently identified in Germany [3] and the ability of JEV to persist and transmit between pigs in absence of mosquitos [4] are increasing risks of virus spread and persistence in regions with more moderate climate and becoming a worldwide public health concern. Vaccination programs are available [5]

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