CX3CR1-CX3CL1-dependent cell-to-cell Japanese encephalitis virus transmission by human microglial cells.

Lannes, Nils; Garcia Nicolas, Obdulio; Demoulins, Thomas; Summerfield, Artur; Filgueira, Luis (2019). CX3CR1-CX3CL1-dependent cell-to-cell Japanese encephalitis virus transmission by human microglial cells. Scientific Reports, 9(1), p. 4833. Nature Publishing Group 10.1038/s41598-019-41302-1

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The neurotropic Japanese encephalitis virus (JEV) is responsible for Japanese encephalitis, an uncontrolled inflammatory disease of the central nervous system. Microglia cells are the unique innate immune cell type populating the brain that cross-communicate with neurons via the CX3CR1-CX3CL1 axis. However, microglia may serve as a viral reservoir for JEV. Human microglia are able to transmit JEV infectivity to neighbouring cells in a cell-to-cell contact-dependent manner. Using JEV-treated human blood monocyte-derived microglia, the present study investigates molecular mechanisms behind cell-to-cell virus transmission by human microglia. For that purpose, JEV-associated microglia were co-cultured with JEV susceptible baby hamster kidney cells under various conditions. Here, we show that microglia hosting JEV for up to 10 days were able to transmit the virus to susceptible cells. Interestingly, neutralizing anti-JEV antibodies did not completely abrogate cell-to-cell virus transmission. Hence, intracellular viral RNA could be a contributing source of infectious virus material upon intercellular interactions. Importantly, the CX3CL1-CX3CR1 axis was a key regulator of cell-to-cell virus transmission from JEV-hosting human microglia. Our findings suggest that human microglia may be a source of infection for neuronal populations and sustain JEV brain pathogenesis in long-term infection. Moreover, the present work emphasizes on the critical role of the CX3CR1-CX3CL1 axis in JEV pathogenesis mediating transmission of infectious genomic JEV RNA.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology

UniBE Contributor:

Garcia Nicolas, Obdulio; Demoulins, Thomas and Summerfield, Artur

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

04 Sep 2019 16:04

Last Modified:

24 Oct 2019 21:50

Publisher DOI:

10.1038/s41598-019-41302-1

PubMed ID:

30886214

BORIS DOI:

10.7892/boris.132995

URI:

https://boris.unibe.ch/id/eprint/132995

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