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Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape following Central Nervous System Infection by a Murine Coronavirus.
J Virol. 2020 11 23; 94(24)JV

Abstract

Intracranial (i.c.) infection of susceptible C57BL/6 mice with the neurotropic JHM strain of mouse hepatitis virus (JHMV) (a member of the Coronaviridae family) results in acute encephalomyelitis and viral persistence associated with an immune-mediated demyelinating disease. The present study was undertaken to better understand the molecular pathways evoked during innate and adaptive immune responses as well as the chronic demyelinating stage of disease in response to JHMV infection of the central nervous system (CNS). Using single-cell RNA sequencing analysis (scRNAseq) on flow-sorted CD45-positive (CD45+) cells enriched from brains and spinal cords of experimental mice, we demonstrate the heterogeneity of the immune response as determined by the presence of unique molecular signatures and pathways involved in effective antiviral host defense. Furthermore, we identify potential genes involved in contributing to demyelination as well as remyelination being expressed by both microglia and macrophages. Collectively, these findings emphasize the diversity of the immune responses and molecular networks at defined stages following viral infection of the CNS.IMPORTANCE Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the molecular signatures of immune cells within the CNS at defined times following infection with a neuroadapted murine coronavirus using scRNAseq. This approach has revealed that the immunological landscape is diverse, with numerous immune cell subsets expressing distinct mRNA expression profiles that are, in part, dictated by the stage of infection. In addition, these findings reveal new insight into cellular pathways contributing to control of viral replication as well as to neurologic disease.

Authors+Show Affiliations

Division of Microbiology & Immunology, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah, USA.Division of Microbiology & Immunology, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah, USA. Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.Division of Microbiology & Immunology, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah, USA.Division of Microbiology & Immunology, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah, USA.Division of Microbiology & Immunology, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah, USA. Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.Division of Microbiology & Immunology, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah, USA tlane@uci.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32999036

Citation

Syage, Amber R., et al. "Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape Following Central Nervous System Infection By a Murine Coronavirus." Journal of Virology, vol. 94, no. 24, 2020.
Syage AR, Ekiz HA, Skinner DD, et al. Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape following Central Nervous System Infection by a Murine Coronavirus. J Virol. 2020;94(24).
Syage, A. R., Ekiz, H. A., Skinner, D. D., Stone, C., O'Connell, R. M., & Lane, T. E. (2020). Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape following Central Nervous System Infection by a Murine Coronavirus. Journal of Virology, 94(24). https://doi.org/10.1128/JVI.01295-20
Syage AR, et al. Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape Following Central Nervous System Infection By a Murine Coronavirus. J Virol. 2020 11 23;94(24) PubMed PMID: 32999036.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape following Central Nervous System Infection by a Murine Coronavirus. AU - Syage,Amber R, AU - Ekiz,H Atakan, AU - Skinner,Dominic D, AU - Stone,Colleen, AU - O'Connell,Ryan M, AU - Lane,Thomas E, Y1 - 2020/11/23/ PY - 2020/06/26/received PY - 2020/09/16/accepted PY - 2020/10/2/pubmed PY - 2020/12/15/medline PY - 2020/10/1/entrez KW - central nervous system KW - central nervous system infections KW - coronavirus KW - host defense KW - immunology KW - neuroimmunology KW - single-cell RNA sequencing JF - Journal of virology JO - J Virol VL - 94 IS - 24 N2 - Intracranial (i.c.) infection of susceptible C57BL/6 mice with the neurotropic JHM strain of mouse hepatitis virus (JHMV) (a member of the Coronaviridae family) results in acute encephalomyelitis and viral persistence associated with an immune-mediated demyelinating disease. The present study was undertaken to better understand the molecular pathways evoked during innate and adaptive immune responses as well as the chronic demyelinating stage of disease in response to JHMV infection of the central nervous system (CNS). Using single-cell RNA sequencing analysis (scRNAseq) on flow-sorted CD45-positive (CD45+) cells enriched from brains and spinal cords of experimental mice, we demonstrate the heterogeneity of the immune response as determined by the presence of unique molecular signatures and pathways involved in effective antiviral host defense. Furthermore, we identify potential genes involved in contributing to demyelination as well as remyelination being expressed by both microglia and macrophages. Collectively, these findings emphasize the diversity of the immune responses and molecular networks at defined stages following viral infection of the CNS.IMPORTANCE Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the molecular signatures of immune cells within the CNS at defined times following infection with a neuroadapted murine coronavirus using scRNAseq. This approach has revealed that the immunological landscape is diverse, with numerous immune cell subsets expressing distinct mRNA expression profiles that are, in part, dictated by the stage of infection. In addition, these findings reveal new insight into cellular pathways contributing to control of viral replication as well as to neurologic disease. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/32999036/Single_Cell_RNA_Sequencing_Reveals_the_Diversity_of_the_Immunological_Landscape_following_Central_Nervous_System_Infection_by_a_Murine_Coronavirus_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=32999036 DB - PRIME DP - Unbound Medicine ER -