Analysis of the host transcriptome from demyelinating spinal cord of murine coronavirus-infected mice

• Published in: PloS one Vol. 8; no. 9; p. e75346
• Main Authors: Elliott, Ruth, Li, Fan, Dragomir, Isabelle, Chua, Ming Ming W, Gregory, Brian D, Weiss, Susan R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.09.2013; Public Library of Science (PLoS)
• Subjects: Adaptor Proteins, Signal Transducing - biosynthesis; Analysis; Animals; Antigen presentation; Antiviral agents; Biocompatibility; Biology; Biomedical materials; Bone marrow; Catabolism; Central nervous system; Coronaviridae; Coronavirus Infections - metabolism; Coronavirus Infections - pathology; Coronaviruses; Cytokines; Cytokines - biosynthesis; Cytokines - metabolism; DAP12 protein; Demyelinating Diseases - metabolism; Demyelinating Diseases - pathology; Demyelinating Diseases - virology; Demyelination; Female; Fibroblasts; Gene expression; Genes; Genetic aspects; Health aspects; Hepatitis; Immune clearance; Infection; Infections; Infiltration; Information systems; Laboratory animals; Lipid metabolism; Lipids; Lymphocytes; Lymphocytes T; Macrophages; Male; Medicine; Membrane Glycoproteins - biosynthesis; Metabolism; Mice; Microglia; Multiple sclerosis; Murine hepatitis virus - metabolism; Myelin; Nerve Tissue Proteins - biosynthesis; Nervous system; Nervous system diseases; Neurodegenerative diseases; Neurological diseases; Next-generation sequencing; Osteoclasts; Persistent infection; Phosphatase; Physiological aspects; Reabsorption; Receptors, Immunologic - biosynthesis; Ribonucleic acid; RNA; Rodents; Spinal cord; Spinal Cord - metabolism; Spinal Cord - pathology; Th1 Cells - metabolism; Th1 Cells - pathology; Transcription; Transcriptome; Virus diseases; Viruses; United States > US; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0075346

Persistent infection of the mouse central nervous system (CNS) with mouse hepatitis virus (MHV) induces a demyelinating disease pathologically similar to multiple sclerosis and is therefore used as a model system. There is little information regarding the host factors that correlate with and contribute to MHV-induced demyelination. Here, we detail the genes and pathways associated with MHV-induced demyelinating disease in the spinal cord. High-throughput sequencing of the host transcriptome revealed that demyelination is accompanied by numerous transcriptional changes indicative of immune infiltration as well as changes in the cytokine milieu and lipid metabolism. We found evidence that a Th1-biased cytokine/chemokine response and eicosanoid-derived inflammation accompany persistent MHV infection and that antigen presentation is ongoing. Interestingly, increased expression of genes involved in lipid transport, processing, and catabolism, including some with known roles in neurodegenerative diseases, coincided with demyelination. Lastly, expression of several genes involved in osteoclast or bone-resident macrophage function, most notably TREM2 and DAP12, was upregulated in persistently infected mouse spinal cord. This study highlights the complexity of the host antiviral response, which accompany MHV-induced demyelination, and further supports previous findings that MHV-induced demyelination is immune-mediated. Interestingly, these data suggest a parallel between bone reabsorption by osteoclasts and myelin debris clearance by microglia in the bone and the CNS, respectively. To our knowledge, this is the first report of using an RNA-seq approach to study the host CNS response to persistent viral infection.