Neuronal transcriptomic responses to Japanese encephalitis virus infection with a special focus on chemokine CXCL11 and pattern recognition receptors RIG-1 and MDA5

Shu Pin Yu; Kien Chai Ong; David Perera; Kum Thong Wong

doi:10.1016/j.virol.2018.10.015

Neuronal transcriptomic responses to Japanese encephalitis virus infection with a special focus on chemokine CXCL11 and pattern recognition receptors RIG-1 and MDA5

Virology. 2019 Jan 15:527:107-115. doi: 10.1016/j.virol.2018.10.015. Epub 2018 Nov 24.

Authors

Shu Pin Yu¹, Kien Chai Ong², David Perera³, Kum Thong Wong⁴

Affiliations

¹ Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
² Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
³ Institute of Health and Community Medicine, University Malaysia Sarawak, Sarawak, Malaysia.
⁴ Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: wongkt@ummc.edu.my.

PMID: 30481615
DOI: 10.1016/j.virol.2018.10.015

Abstract

Japanese encephalitis virus (JEV) causes central nervous system neuronal injury and inflammation. A clear understanding of neuronal responses to JEV infection remains elusive. Using the Affymetrix array to investigate the transcriptome of infected SK-N-MC cells, 1316 and 2737 dysregulated genes (≥ 2/-2 fold change, P < 0.05) were found at 48 hours post-infection (hpi) and 60 hpi, respectively. The genes were mainly involved in anti-microbial responses, cell signalling, cellular function and maintenance, and cell death and survival. Among the most highly upregulated genes (≥ 10 folds, P < 0.05) were chemokines CCL5, CXCL11, IL8 and CXCL10. The upregulation and expression of CXCL11 were confirmed by qRT-PCR and immunofluorescence. Pathogen recognition receptors retinoic acid-inducible gene-1 (RIG-1) and melanoma differentiation-associated protein 5 (MDA5) were also upregulated. Our results strongly suggest that neuronal cells play a significant role in immunity against JEV. CXCL11, RIG-1 and MDA5 and other cytokines may be important in neuropathogenesis.

Keywords: CXCL11; Japanese encephalitis virus; MDA5; Neuronal infection; Proinflammatory mediators; RIG-1; RNA microarray; Transcriptome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Viral / metabolism
Cell Line
Chemokine CXCL11 / genetics*
Chemokine CXCL11 / metabolism
DEAD Box Protein 58 / genetics*
Encephalitis Virus, Japanese / immunology
Encephalitis Virus, Japanese / physiology*
Encephalitis, Japanese / virology*
Gene Expression Profiling
Humans
Interferon-Induced Helicase, IFIH1 / genetics*
Neurons / virology*
Oligonucleotide Array Sequence Analysis
Receptors, Immunologic
Up-Regulation

Substances

Antigens, Viral
CXCL11 protein, human
Chemokine CXCL11
Receptors, Immunologic
RIGI protein, human
IFIH1 protein, human
DEAD Box Protein 58
Interferon-Induced Helicase, IFIH1