{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:29:48Z","timestamp":1788791388045,"version":"build-2803163510"},"reference-count":119,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Neurotropic viruses have evolved sophisticated mechanisms to evade host immune responses within the central nervous system (CNS), enabling viral replication, persistence, latency, and neuropathogenesis while minimizing irreversible neuronal damage. Unlike peripheral tissues, the CNS requires tightly regulated antiviral immunity to balance effective pathogen control with the preservation of neural function. This review examines the diverse yet convergent immune evasion strategies employed by major neurotropic RNA and DNA viruses, including herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), rabies virus (RABV), flaviviruses, alphaviruses, enteroviruses, and JC virus (JCV). We discuss viral interference with innate immune sensing pathways, including RIG-I-like receptors (RLRs) and cyclic GMP\u2013AMP synthase\u2013stimulator of interferon genes (cGAS\u2013STING) signaling, inhibition of type I interferon induction and Janus kinase\u2013signal transducer and activator of transcription (JAK\u2013STAT) signaling, modulation of interferon-stimulated effector mechanisms, and disruption of antigen presentation and adaptive immune surveillance. The review further highlights the distinct roles of viral latency, long-term persistence, neuronal\u2013glial interactions, and metabolic reprogramming in facilitating prolonged infection within the CNS. Emerging evidence indicates that successful neurotropic viruses rarely achieve immune evasion through complete suppression of host defenses; instead, they fine-tune antiviral responses to preserve host cell viability while preventing viral clearance. Finally, we discuss current knowledge gaps and emphasize the need for advanced human-relevant models, single-cell and spatial multi-omics, and systems-level approaches to better define virus\u2013host interactions within the CNS. A deeper understanding of these integrated immune evasion networks may reveal novel therapeutic strategies that enhance antiviral immunity while limiting neuroinflammation and preserving neurological function.<\/jats:p>","DOI":"10.3390\/ijms27177962","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"7962","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune Evasion by Neurotropic Viruses: Molecular Strategies, Cellular Targets, and Consequences for CNS Infection"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9514-0884","authenticated-orcid":false,"given":"Antonios","family":"Mouzakis","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9065-4811","authenticated-orcid":false,"given":"Vasileios","family":"Petrakis","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Second Department of Internal Medicine, University General Hospital Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4952-0675","authenticated-orcid":false,"given":"Katerina","family":"Chlichlia","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nri1105","article-title":"Immune responses to RNA-virus infections of the CNS","volume":"3","author":"Griffin","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nri2971","article-title":"Illuminating viral infections in the nervous system","volume":"11","author":"McGavern","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.chom.2013.03.010","article-title":"Virus infections in the nervous system","volume":"13","author":"Koyuncu","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Vazquez, C., and Jurado, K.A. (2022). Neurotropic RNA Virus Modulation of Immune Responses within the Central Nervous System. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23074018"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"834","DOI":"10.3390\/v5030834","article-title":"Antiviral type I and type III interferon responses in the central nervous system","volume":"5","author":"Sorgeloos","year":"2013","journal-title":"Viruses"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nri3265","article-title":"The anatomical and cellular basis of immune surveillance in the central nervous system","volume":"12","author":"Ransohoff","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1600-065X.2006.00441.x","article-title":"CNS immune privilege: Hiding in plain sight","volume":"213","author":"Carson","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.it.2013.10.012","article-title":"Innate antiviral signalling in the central nervous system","volume":"35","author":"Carty","year":"2014","journal-title":"Trends Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lang, R., Li, H., Luo, X., Liu, C., Zhang, Y., Guo, S., Xu, J., Bao, C., Dong, W., and Yu, Y. (2022). Expression and mechanisms of interferon-stimulated genes in viral infection of the central nervous system (CNS) and neurological diseases. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1008072"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12974-018-1119-3","article-title":"Cell-type- and region-specific restriction of neurotropic flavivirus infection by viperin","volume":"15","author":"Lindqvist","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.it.2019.07.005","article-title":"Interferon Control of Neurotropic Viral Infections","volume":"40","author":"Milora","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/s41577-020-0288-3","article-title":"RIG-I-like receptors: Their regulation and roles in RNA sensing","volume":"20","author":"Rehwinkel","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.immuni.2011.05.003","article-title":"Immune signaling by RIG-I-like receptors","volume":"34","author":"Loo","year":"2011","journal-title":"Immunity"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e01155-16","DOI":"10.1128\/JVI.01155-16","article-title":"Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes","volume":"91","author":"Wolff","year":"2017","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e01960-17","DOI":"10.1128\/JVI.01960-17","article-title":"Paramyxovirus V Proteins Interact with the RIG-I\/TRIM25 Regulatory Complex and Inhibit RIG-I Signaling","volume":"92","author":"Feinman","year":"2018","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.chom.2009.04.006","article-title":"Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I","volume":"5","author":"Gack","year":"2009","journal-title":"Cell Host Microbe"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.mib.2016.05.015","article-title":"Innate immune evasion strategies of DNA and RNA viruses","volume":"32","author":"Beachboard","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17264","DOI":"10.1073\/pnas.0407639101","article-title":"The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter","volume":"101","author":"Andrejeva","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1126\/science.1230949","article-title":"Paramyxovirus V proteins disrupt the fold of the RNA sensor MDA5 to inhibit antiviral signaling","volume":"339","author":"Motz","year":"2013","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1128\/JVI.80.6.2675-2683.2006","article-title":"Inhibition of interferon signaling by rabies virus phosphoprotein P: Activation-dependent binding of STAT1 and STAT2","volume":"80","author":"Finke","year":"2006","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14411","DOI":"10.1128\/JVI.79.22.14411-14420.2005","article-title":"Rabies virus P protein interacts with STAT1 and inhibits interferon signal transduction pathways","volume":"79","author":"Vidy","year":"2005","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1128\/JVI.02712-13","article-title":"Enterovirus 2Apro targets MDA5 and MAVS in infected cells","volume":"88","author":"Feng","year":"2014","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/B978-0-12-385034-8.00004-1","article-title":"Innate host barriers to viral trafficking and population diversity: Lessons learned from poliovirus","volume":"77","author":"Pfeiffer","year":"2010","journal-title":"Adv. Virus Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wang, B., Xi, X., Lei, X., Zhang, X., Cui, S., Wang, J., Jin, Q., and Zhao, Z. (2013). Enterovirus 71 protease 2Apro targets MAVS to inhibit anti-viral type I interferon responses. PLoS Pathog., 9, Correction in PLoS Pathog. 2017, 13, e1006243. https:\/\/doi.org\/10.1371\/journal.ppat.1006243. Correction in PLoS Pathog. 2024, 20, e1012209. https:\/\/doi.org\/10.1371\/journal.ppat.1012209.","DOI":"10.1371\/journal.ppat.1006243"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1126\/science.1232458","article-title":"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway","volume":"339","author":"Sun","year":"2013","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/ni.3558","article-title":"Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing","volume":"17","author":"Chen","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eaat8657","DOI":"10.1126\/science.aat8657","article-title":"cGAS in action: Expanding roles in immunity and inflammation","volume":"363","author":"Ablasser","year":"2019","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1084\/jem.20180139","article-title":"The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer","volume":"215","author":"Li","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.chom.2018.07.004","article-title":"Species-Specific Deamidation of cGAS by Herpes Simplex Virus UL37 Protein Facilitates Viral Replication","volume":"24","author":"Zhang","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E3008","DOI":"10.1073\/pnas.1211302109","article-title":"Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection and degradation of IFI16 by the viral ICP0 protein","volume":"109","author":"Orzalli","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E4492","DOI":"10.1073\/pnas.1316194110","article-title":"Nuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA","volume":"110","author":"Orzalli","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1128\/MMBR.00040-07","article-title":"Tegument proteins of human cytomegalovirus","volume":"72","author":"Kalejta","year":"2008","journal-title":"Microbiol. Mol. Biol. Rev. MMBR"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Paijo, J., D\u00f6ring, M., Spanier, J., Grabski, E., Nooruzzaman, M., Schmidt, T., Witte, G., Messerle, M., Hornung, V., and Kaever, V. (2016). CGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005546"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.chom.2017.01.001","article-title":"Human Cytomegalovirus Tegument Protein UL82 Inhibits STING-Mediated Signaling to Evade Antiviral Immunity","volume":"21","author":"Fu","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.immuni.2006.08.009","article-title":"Type I Inteferon Gene Induction by the Interferon Regulatory Factor Family of Transcription Factors","volume":"25","author":"Honda","year":"2006","journal-title":"Immunity"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ni921","article-title":"IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway","volume":"4","author":"Fitzgerald","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1126\/science.1081315","article-title":"Triggering the interferon antiviral response through an IKK-related pathway","volume":"300","author":"Sharma","year":"2003","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1128\/JVI.00082-13","article-title":"Herpes simplex virus 1 infection induces activation and subsequent inhibition of the IFI16 and NLRP3 inflammasomes","volume":"87","author":"Johnson","year":"2013","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12814","DOI":"10.1128\/JVI.02355-13","article-title":"Herpes simplex virus 1 serine\/threonine kinase US3 hyperphosphorylates IRF3 and inhibits beta interferon production","volume":"87","author":"Wang","year":"2013","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fros, J.J., and Pijlman, G.P. (2016). Alphavirus Infection: Host Cell Shut-Off and Inhibition of Antiviral Responses. Viruses, 8.","DOI":"10.3390\/v8060166"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5686","DOI":"10.1128\/JVI.02739-05","article-title":"Sindbis virus nonstructural protein nsP2 is cytotoxic and inhibits cellular transcription","volume":"80","author":"Garmashova","year":"2006","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8677","DOI":"10.1128\/JVI.02411-06","article-title":"Semliki Forest virus nonstructural protein 2 is involved in suppression of the type I interferon response","volume":"81","author":"Breakwell","year":"2007","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9349","DOI":"10.1128\/JVI.01122-06","article-title":"Pathogenesis of West Nile Virus infection: A balance between virulence, innate and adaptive immunity, and viral evasion","volume":"80","author":"Samuel","year":"2006","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"284ra59","DOI":"10.1126\/scitranslmed.aaa4304","article-title":"Interferon-\u03bb restricts West Nile virus neuroinvasion by tightening the blood-brain barrier","volume":"7","author":"Lazear","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nm.3108","article-title":"Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses","volume":"19","author":"Cho","year":"2013","journal-title":"Nat. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.immuni.2012.03.013","article-title":"The JAK-STAT pathway at twenty","volume":"36","author":"Stark","year":"2012","journal-title":"Immunity"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nri3581","article-title":"Regulation of type I interferon responses","volume":"14","author":"Ivashkiv","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri1604","article-title":"Mechanisms of type-I- and type-II-interferon-mediated signalling","volume":"5","author":"Platanias","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.chom.2016.05.009","article-title":"Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling","volume":"19","author":"Grant","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.15252\/embr.201642627","article-title":"Zika virus inhibits type-I interferon production and downstream signaling","volume":"17","author":"Kumar","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.1128\/JVI.02188-08","article-title":"NS5 of dengue virus mediates STAT2 binding and degradation","volume":"83","author":"Ashour","year":"2009","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.chom.2014.07.015","article-title":"The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by type I interferon","volume":"16","author":"Morrison","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11476","DOI":"10.1128\/JVI.76.22.11476-11483.2002","article-title":"Nipah virus V protein evades alpha and gamma interferons by preventing STAT1 and STAT2 activation and nuclear accumulation","volume":"76","author":"Rodriguez","year":"2002","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11842","DOI":"10.1128\/JVI.77.21.11842-11845.2003","article-title":"Hendra virus V protein inhibits interferon signaling by preventing STAT1 and STAT2 nuclear accumulation","volume":"77","author":"Rodriguez","year":"2003","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1128\/JVI.02075-06","article-title":"Capsid protein of eastern equine encephalitis virus inhibits host cell gene expression","volume":"81","author":"Aguilar","year":"2007","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1128\/JVI.02858-12","article-title":"Neurotropic arboviruses induce interferon regulatory factor 3-mediated neuronal responses that are cytoprotective, interferon independent, and inhibited by Western equine encephalitis virus capsid","volume":"87","author":"Peltier","year":"2013","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10394","DOI":"10.1128\/JVI.00884-13","article-title":"The C-terminal domain of chikungunya virus nsP2 independently governs viral RNA replication, cytopathicity, and inhibition of interferon signaling","volume":"87","author":"Fros","year":"2013","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e01008-18","DOI":"10.1128\/JVI.01008-18","article-title":"The Methyltransferase-Like Domain of Chikungunya Virus nsP2 Inhibits the Interferon Response by Promoting the Nuclear Export of STAT1","volume":"92","author":"McNally","year":"2018","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.1128\/JVI.01930-06","article-title":"The nucleocytoplasmic rabies virus P protein counteracts interferon signaling by inhibiting both nuclear accumulation and DNA binding of STAT1","volume":"81","author":"Vidy","year":"2007","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.biochi.2007.03.001","article-title":"The dsRNA protein kinase PKR: Virus and cell control","volume":"89","author":"Meurs","year":"2007","journal-title":"Biochimie"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1073\/pnas.94.3.843","article-title":"The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase","volume":"94","author":"He","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nrmicro2655","article-title":"Viral subversion of the host protein synthesis machinery","volume":"9","author":"Walsh","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"12720","DOI":"10.1128\/JVI.01471-07","article-title":"Viral encounters with 2\u2032,5\u2032-oligoadenylate synthetase and RNase L during the interferon antiviral response","volume":"81","author":"Silverman","year":"2007","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.coviro.2015.07.002","article-title":"Inhibition of the OAS\/RNase L pathway by viruses","volume":"15","author":"Drappier","year":"2015","journal-title":"Curr. Opin. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"eads9407","DOI":"10.1126\/sciimmunol.ads9407","article-title":"The OAS-RNase L pathway: Insights from experiments of nature","volume":"11","author":"Lee","year":"2026","journal-title":"Sci. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.virol.2015.03.012","article-title":"APOBECs and virus restriction","volume":"479\u2013480","author":"Harris","year":"2015","journal-title":"Virology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4858","DOI":"10.1073\/pnas.1009687108","article-title":"Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism","volume":"108","author":"Aynaud","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Cheng, A.Z., Moraes, S.N., Shaban, N.M., Fanunza, E., Bierle, C.J., Southern, P.J., Bresnahan, W.A., Rice, S.A., and Harris, R.S. (2021). APOBECs and Herpesviruses. Viruses, 13.","DOI":"10.3390\/v13030390"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: A complex web of host defenses","volume":"32","author":"Schneider","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.coviro.2014.03.006","article-title":"Interferon-stimulated genes: Roles in viral pathogenesis","volume":"6","author":"Schoggins","year":"2014","journal-title":"Curr. Opin. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1099\/vir.0.83391-0","article-title":"Interferons and viruses: An interplay between induction, signalling, antiviral responses and virus countermeasures","volume":"89","author":"Randall","year":"2008","journal-title":"J. General. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1006\/jmbi.1997.1282","article-title":"The active domain of the herpes simplex virus protein ICP47: A potent inhibitor of the transporter associated with antigen processing","volume":"272","author":"Neumann","year":"1997","journal-title":"J. Mol. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/375415a0","article-title":"A viral inhibitor of peptide transporters for antigen presentation","volume":"375","author":"Ahn","year":"1995","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/375411a0","article-title":"Herpes simplex virus turns off the TAP to evade host immunity","volume":"375","author":"Hill","year":"1995","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nri2575","article-title":"MHC class I antigen presentation: Learning from viral evasion strategies","volume":"9","author":"Hansen","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S0092-8674(00)81054-5","article-title":"The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol","volume":"84","author":"Wiertz","year":"1996","journal-title":"Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S1074-7613(00)80349-0","article-title":"The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP","volume":"6","author":"Ahn","year":"1997","journal-title":"Immunity"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"102646","DOI":"10.1016\/j.conb.2022.102646","article-title":"Glia as antigen-presenting cells in the central nervous system","volume":"77","author":"Sutter","year":"2022","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.immuni.2022.04.012","article-title":"Immunological defense of CNS barriers against infections","volume":"55","author":"Ampie","year":"2022","journal-title":"Immunity"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1111\/j.1574-6976.2011.00320.x","article-title":"The molecular basis of herpes simplex virus latency","volume":"36","author":"Nicoll","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nrmicro1794","article-title":"Chromatin control of herpes simplex virus lytic and latent infection","volume":"6","author":"Knipe","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e01419-16","DOI":"10.1128\/JVI.01419-16","article-title":"Restarting Lytic Gene Transcription at the Onset of Herpes Simplex Virus Reactivation","volume":"91","author":"Cliffe","year":"2017","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"St Leger, A.J., Koelle, D.M., Kinchington, P.R., and Verjans, G.M.G.M. (2021). Local Immune Control of Latent Herpes Simplex Virus Type 1 in Ganglia of Mice and Man. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.723809"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s12974-022-02611-x","article-title":"T-cells in human trigeminal ganglia express canonical tissue-resident memory T-cell markers","volume":"19","author":"Unger","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Verzosa, A.L., McGeever, L.A., Bhark, S.J., Delgado, T., Salazar, N., and Sanchez, E.L. (2021). Herpes Simplex Virus 1 Infection of Neuronal and Non-Neuronal Cells Elicits Specific Innate Immune Responses and Immune Evasion Mechanisms. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.644664"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/rmv.362","article-title":"Varicella-zoster virus latency in human ganglia","volume":"12","author":"Kennedy","year":"2002","journal-title":"Rev. Med. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrmicro3215","article-title":"Molecular mechanisms of varicella zoster virus pathogenesis","volume":"12","author":"Zerboni","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1474-4422(10)70040-5","article-title":"Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: Clinical features and pathogenesis","volume":"9","author":"Tan","year":"2010","journal-title":"Lancet. Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/infdis\/jir256","article-title":"Sequencing and analysis of JC virus DNA from natalizumab-treated PML patients","volume":"204","author":"Reid","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.12688\/f1000research.7071.1","article-title":"Progressive Multifocal Leukoencephalopathy","volume":"4","author":"Adang","year":"2015","journal-title":"F1000Research"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.immuni.2017.06.012","article-title":"Protective and Pathological Immunity during Central Nervous System Infections","volume":"46","author":"Klein","year":"2017","journal-title":"Immunity"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/nature07103","article-title":"MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs","volume":"454","author":"Umbach","year":"2008","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.bbagrm.2011.06.012","article-title":"Viral miRNAs and immune evasion","volume":"1809","author":"Boss","year":"2011","journal-title":"Biochim. Et. Biophys. Acta"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.coi.2021.07.004","article-title":"Neuron-intrinsic immunity to viruses in mice and humans","volume":"72","author":"Zhang","year":"2021","journal-title":"Curr. Opin. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Paolicelli, R.C., Bisht, K., and Tremblay, M.\u00c8. (2014). Fractalkine regulation of microglial physiology and consequences on the brain and behavior. Front. Cell. Neurosci., 8.","DOI":"10.3389\/fncel.2014.00129"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.tins.2007.08.007","article-title":"Neuronal \u2018On\u2019 and \u2018Off\u2019 signals control microglia","volume":"30","author":"Biber","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1126\/science.290.5497.1768","article-title":"Down-regulation of the macrophage lineage through interaction with OX2 (CD200)","volume":"290","author":"Hoek","year":"2000","journal-title":"Science"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","article-title":"Astrocytes: Biology and pathology","volume":"119","author":"Sofroniew","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.immuni.2017.06.006","article-title":"Reactive Astrocytes: Production, Function, and Therapeutic Potential","volume":"46","author":"Liddelow","year":"2017","journal-title":"Immunity"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41423-020-00620-5","article-title":"The roles of microglia in viral encephalitis: From sensome to therapeutic targeting","volume":"18","author":"Chhatbar","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/glia.22375","article-title":"Oligodendroglia are limited in type I interferon induction and responsiveness in vivo","volume":"60","author":"Kapil","year":"2012","journal-title":"Glia"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s13365-023-01164-w","article-title":"Revisiting JC virus and progressive multifocal leukoencephalopathy","volume":"29","author":"Rocchi","year":"2023","journal-title":"J. Neurovirology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41582-023-00809-y","article-title":"Single-cell and spatial transcriptomics: Deciphering brain complexity in health and disease","volume":"19","author":"Piwecka","year":"2023","journal-title":"Nat. Rev. Neurol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10571-024-01499-w","article-title":"Advancements in Single-Cell RNA Sequencing and Spatial Transcriptomics for Central Nervous System Disease","volume":"44","author":"Zhang","year":"2024","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s40478-023-01547-4","article-title":"Temporal tracking of microglial and monocyte single-cell transcriptomics in lethal flavivirus infection","volume":"11","author":"Spiteri","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12974-025-03471-x","article-title":"Temporally resolved single-cell RNA sequencing reveals protective and pathological responses during herpes simplex virus CNS infection","volume":"22","author":"Ding","year":"2025","journal-title":"J. Neuroinflammation"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Rangel, M.V., Sebastian, A., Leon, N.F., Phillips, A.M., Gorman, B.M., Hum, N.R., and Weilhammer, D.R. (2024). Single-cell and spatiotemporal transcriptomic profiling of brain immune infiltration following Venezuelan equine encephalitis virus infection. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1497839"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e2515006122","DOI":"10.1073\/pnas.2515006122","article-title":"Spatial gene expression analysis reveals pathological niches in Japanese encephalitis virus neuroinvasion","volume":"122","author":"Orba","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e01295-20","DOI":"10.1128\/JVI.01295-20","article-title":"Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape following Central Nervous System Infection by a Murine Coronavirus","volume":"94","author":"Syage","year":"2020","journal-title":"J. Virol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"105268","DOI":"10.1016\/j.micinf.2023.105268","article-title":"Dissecting viral infections, one cell at a time, by single-cell technologies","volume":"26","author":"Bost","year":"2024","journal-title":"Microbes Infect."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.immuni.2013.04.005","article-title":"Metabolic pathways in immune cell activation and quiescence","volume":"38","author":"Pearce","year":"2013","journal-title":"Immunity"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/bph.13139","article-title":"Microglial M1\/M2 polarization and metabolic states","volume":"173","author":"Orihuela","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.coi.2015.06.011","article-title":"Innate immune interactions within the central nervous system modulate pathogenesis of viral infections","volume":"36","author":"Nair","year":"2015","journal-title":"Curr. Opin. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Thaker, S.K., Ch\u2019ng, J., and Christofk, H.R. (2019). Viral hijacking of cellular metabolism. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0678-9"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.virol.2015.02.038","article-title":"Viral activation of cellular metabolism","volume":"479\u2013480","author":"Sanchez","year":"2015","journal-title":"Virology"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1128\/JVI.02309-14","article-title":"Dengue virus induces and requires glycolysis for optimal replication","volume":"89","author":"Fontaine","year":"2015","journal-title":"J. Virol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1111\/febs.15871","article-title":"Mechanisms of viral persistence in the brain and therapeutic approaches","volume":"289","author":"Nath","year":"2022","journal-title":"FEBS J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/s41423-024-01181-7","article-title":"Orchestration of antiviral responses within the infected central nervous system","volume":"21","author":"Pavlou","year":"2024","journal-title":"Cell. Mol. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s40263-024-01082-3","article-title":"CNS Viral Infections\u2014What to Consider for Improving Drug Treatment: A Plea for Using Mathematical Modeling Approaches","volume":"38","author":"Sun","year":"2024","journal-title":"CNS Drugs"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7962\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:00:21Z","timestamp":1788789621000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":119,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177962"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177962","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]}}}