Single-cell RNA sequencing reveals the immune features and viral tropism in the central nervous system of mice infected with Japanese encephalitis virus.

Publisher: BioMed Central Country of Publication: England NLM ID: 101222974 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-2094 (Electronic) Linking ISSN: 17422094 NLM ISO Abbreviation: J Neuroinflammation Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2004-

Encephalitis Virus, Japanese* ; Encephalitis Viruses, Japanese* ; Encephalitis, Japanese*/pathology; Mice ; Animals ; Viral Tropism ; Central Nervous System/pathology ; Inflammation ; Sequence Analysis, RNA

Japanese encephalitis virus (JEV) is a neurotropic pathogen that causes lethal encephalitis. The high susceptibility and massive proliferation of JEV in neurons lead to extensive neuronal damage and inflammation within the central nervous system. Despite extensive research on JEV pathogenesis, the effect of JEV on the cellular composition and viral tropism towards distinct neuronal subtypes in the brain is still not well comprehended. To address these issues, we performed single-cell RNA sequencing (scRNA-seq) on cells isolated from the JEV-highly infected regions of mouse brain. We obtained 88,000 single cells and identified 34 clusters representing 10 major cell types. The scRNA-seq results revealed an increasing amount of activated microglia cells and infiltrating immune cells, including monocytes & macrophages, T cells, and natural killer cells, which were associated with the severity of symptoms. Additionally, we observed enhanced communication between individual cells and significant ligand-receptor pairs related to tight junctions, chemokines and antigen-presenting molecules upon JEV infection, suggesting an upregulation of endothelial permeability, inflammation and antiviral response. Moreover, we identified that Baiap2-positive neurons were highly susceptible to JEV. Our findings provide valuable clues for understanding the mechanism of JEV induced neuro-damage and inflammation as well as developing therapies for Japanese encephalitis.
(© 2024. The Author(s).)

Neurochem Int. 2011 Feb;58(2):234-42. (PMID: 21167894)
Cell. 2020 Feb 20;180(4):764-779.e20. (PMID: 32059779)
Nature. 2023 Feb;614(7947):309-317. (PMID: 36599977)
J Virol. 2017 Feb 28;91(6):. (PMID: 28053106)
Virus Res. 2014 Jun 24;185:32-40. (PMID: 24657789)
Cell. 2020 Jun 11;181(6):1346-1363.e21. (PMID: 32473126)
Nat Methods. 2016 Oct;13(10):845-8. (PMID: 27571553)
Virol J. 2007 Sep 06;4:83. (PMID: 17803826)
Prog Neurobiol. 2010 Jun;91(2):108-20. (PMID: 20132860)
Intervirology. 2015;58(2):130-7. (PMID: 25925196)
Curr Protoc Immunol. 2018 Apr;121(1):e44. (PMID: 30040211)
Nat Commun. 2023 Apr 29;14(1):2476. (PMID: 37120617)
Int J Oral Sci. 2021 Nov 15;13(1):36. (PMID: 34782601)
Neuron. 2021 Jan 6;109(1):11-26. (PMID: 33412093)
Mol Aspects Med. 2021 Oct;81:100994. (PMID: 34274157)
Immunity. 2012 Dec 14;37(6):1009-23. (PMID: 23219391)
PLoS Negl Trop Dis. 2009 Sep 29;3(9):e437. (PMID: 19787040)
J Neuroinflammation. 2018 Aug 25;15(1):238. (PMID: 30144801)
Nat Commun. 2022 Mar 4;13(1):1169. (PMID: 35246514)
Front Immunol. 2017 Sep 29;8:1237. (PMID: 29033949)
Pathogens. 2023 Feb 17;12(2):. (PMID: 36839614)
Cell. 2018 Aug 9;174(4):1015-1030.e16. (PMID: 30096299)
Virol J. 2011 Feb 24;8:80. (PMID: 21345237)
Immunity. 2019 Jan 15;50(1):253-271.e6. (PMID: 30471926)
Immunity. 2020 Sep 15;53(3):685-696.e3. (PMID: 32783921)
Arch Virol. 1993;130(3-4):477-84. (PMID: 8517798)
J Virol. 2014 May;88(9):4798-810. (PMID: 24522920)
J Comp Neurol. 2014 Jun 15;522(9):2164-78. (PMID: 24639075)
PLoS Negl Trop Dis. 2021 Jun 21;15(6):e0008442. (PMID: 34153060)
Clin Transl Med. 2022 Jan;12(1):e700. (PMID: 35051311)
Nat Med. 2019 Feb;25(2):270-276. (PMID: 30643288)
Nat Immunol. 2022 Jun;23(6):971-984. (PMID: 35624211)
Nat Commun. 2017 Nov 2;8(1):1262. (PMID: 29093445)
Cell. 2021 Apr 1;184(7):1895-1913.e19. (PMID: 33657410)
Elife. 2022 Nov 01;11:. (PMID: 36317872)
Viruses. 2020 Mar 24;12(3):. (PMID: 32213866)
J Immunol Res. 2014;2014:787023. (PMID: 25101306)
Brain Behav Immun. 2017 Nov;66:230-243. (PMID: 28690034)
Hum Vaccin Immunother. 2017 Jun 3;13(6):1-18. (PMID: 28301270)
Metab Brain Dis. 2022 Jun;37(5):1487-1502. (PMID: 35486209)
Nat Neurosci. 2022 May;25(5):577-587. (PMID: 35524140)
Sci Signal. 2016 Oct 04;9(448):ra98. (PMID: 27703031)
Cell Stem Cell. 2024 Feb 1;31(2):196-211.e6. (PMID: 38237586)
Front Cell Infect Microbiol. 2021 Aug 31;11:701820. (PMID: 34532298)
Nat Commun. 2021 Feb 17;12(1):1088. (PMID: 33597522)
Glia. 2015 Nov;63(11):1915-1932. (PMID: 25959931)
J Virol. 2015 May;89(10):5602-14. (PMID: 25762733)
Bull World Health Organ. 2011 Oct 1;89(10):766-74, 774A-774E. (PMID: 22084515)
Emerg Microbes Infect. 2023 Dec;12(1):2186608. (PMID: 36880345)
Neuropharmacology. 2016 Jan;100:27-39. (PMID: 26275848)
Clin Transl Med. 2022 Mar;12(3):e694. (PMID: 35352511)
Nat Commun. 2020 Nov 30;11(1):6129. (PMID: 33257666)
J Neurochem. 2008 Aug;106(4):1624-36. (PMID: 18540995)
J Neurovirol. 2014 Dec;20(6):539-60. (PMID: 25287260)
Cell Discov. 2020 Dec 8;6(1):90. (PMID: 33298893)
Virol J. 2011 Mar 20;8:128. (PMID: 21418596)
Nat Neurosci. 2017 Sep;20(9):1300-1309. (PMID: 28758994)
Nat Immunol. 2006 Feb;7(2):131-7. (PMID: 16424890)
Front Cell Dev Biol. 2020 Dec 08;8:613733. (PMID: 33364241)
PLoS Pathog. 2018 Jul 20;14(7):e1007189. (PMID: 30028877)
J Gen Virol. 2011 Dec;92(Pt 12):2803-2809. (PMID: 21813703)
Neuron. 2023 Mar 1;111(5):696-710.e9. (PMID: 36603584)
Front Immunol. 2022 Jan 28;13:829433. (PMID: 35154151)
Sci Rep. 2023 Apr 13;13(1):6063. (PMID: 37055489)
Virulence. 2021 Dec;12(1):968-980. (PMID: 33724154)

32030107 National Natural Science Foundation of China; 32022082 National Natural Science Foundation of China; 2022YFD1800105 National Key Research and Development Program of China; 2022YFD1801500 National Key Research and Development Program of China; 2662023PY005 Fundamental Research Funds for the Central Universities

Keywords: Baiap2; Inflammation; JEV; Neuron; scRNA-seq

Date Created: 20240327 Date Completed: 20240328 Latest Revision: 20240329

20250114

PMC10967088

10.1186/s12974-024-03071-1

38532383