{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T16:55:12Z","timestamp":1794243312784,"version":"4.9.0"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31971373"],"award-info":[{"award-number":["31971373"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-025-59042-4","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T09:22:26Z","timestamp":1744968146000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A microengineered 3D human neurovascular unit model to probe the neuropathogenesis of herpes simplex encephalitis"],"prefix":"10.1038","volume":"16","author":[{"given":"Min","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6273-9140","authenticated-orcid":false,"given":"Lin","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengwei","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4472-7079","authenticated-orcid":false,"given":"Rongcan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqiong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5766-0198","authenticated-orcid":false,"given":"Yingtong","family":"Di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5735-6436","authenticated-orcid":false,"given":"Jianhua","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"59042_CR1","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.tim.2020.03.003","volume":"28","author":"ME Marcocci","year":"2020","unstructured":"Marcocci, M. E. et al. Herpes simplex virus-1 in the brain: the dark side of a sneaky infection. Trends Microbiol. 28, 808\u2013820 (2020).","journal-title":"Trends Microbiol."},{"key":"59042_CR2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1097\/QCO.0000000000000554","volume":"32","author":"JP Stahl","year":"2019","unstructured":"Stahl, J. P. & Mailles, A. Herpes simplex virus encephalitis update. Curr. Opin. Infect. Dis. 32, 239\u2013243 (2019).","journal-title":"Curr. Opin. Infect. Dis."},{"key":"59042_CR3","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-017-0568-7","volume":"19","author":"JW Gnann Jr.","year":"2017","unstructured":"Gnann, J. W. Jr. & Whitley, R. J. Herpes simplex encephalitis: an update. Curr. Infect. Dis. Rep. 19, 13 (2017).","journal-title":"Curr. Infect. Dis. Rep."},{"key":"59042_CR4","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/s13311-016-0433-7","volume":"13","author":"MJ Bradshaw","year":"2016","unstructured":"Bradshaw, M. J. & Venkatesan, A. Herpes simplex virus-1 encephalitis in adults: pathophysiology, diagnosis, and management. Neurotherapeutics 13, 493\u2013508 (2016).","journal-title":"Neurotherapeutics"},{"key":"59042_CR5","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s13365-019-00752-z","volume":"25","author":"H Liu","year":"2019","unstructured":"Liu, H. et al. Proteomics analysis of HSV-1-induced alterations in mouse brain microvascular endothelial cells. J. Neurovirol. 25, 525\u2013539 (2019).","journal-title":"J. Neurovirol."},{"key":"59042_CR6","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1001\/archneur.1986.00520040003001","volume":"43","author":"MJ Ball","year":"1986","unstructured":"Ball, M. J. Herpesvirus in the hippocampus as a cause of Alzheimer\u2019s disease. Arch. Neurol. 43, 313 (1986).","journal-title":"Arch. Neurol."},{"key":"59042_CR7","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0140-6736(96)10149-5","volume":"349","author":"RF Itzhaki","year":"1997","unstructured":"Itzhaki, R. F. et al. Herpes simplex virus type 1 in brain and risk of Alzheimer\u2019s disease. Lancet 349, 241\u2013244 (1997).","journal-title":"Lancet"},{"key":"59042_CR8","first-page":"332","volume":"125","author":"RA Sobel","year":"1986","unstructured":"Sobel, R. A. et al. The in situ cellular immune response in acute herpes simplex encephalitis. Am. J. Pathol. 125, 332\u2013338 (1986).","journal-title":"Am. J. Pathol."},{"key":"59042_CR9","doi-asserted-by":"publisher","first-page":"732820","DOI":"10.3389\/fcell.2021.732820","volume":"9","author":"EC Kugler","year":"2021","unstructured":"Kugler, E. C., Greenwood, J. & MacDonald, R. B. The \u201cneuro-glial-vascular\u201d unit: the role of glia in neurovascular unit formation and dysfunction. Front. Cell Dev. Biol. 9, 732820 (2021).","journal-title":"Front. Cell Dev. Biol."},{"key":"59042_CR10","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1007\/s10571-021-01113-3","volume":"42","author":"O Naranjo","year":"2022","unstructured":"Naranjo, O. et al. In vivo targeting of the neurovascular unit: challenges and advancements. Cell Mol. Neurobiol. 42, 2131\u20132146 (2022).","journal-title":"Cell Mol. Neurobiol."},{"key":"59042_CR11","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.arr.2016.09.006","volume":"34","author":"W Cai","year":"2017","unstructured":"Cai, W. et al. Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: an aging effect. Ageing Res. Rev. 34, 77\u201387 (2017).","journal-title":"Ageing Res. Rev."},{"key":"59042_CR12","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12987-022-00316-0","volume":"19","author":"P Zarekiani","year":"2022","unstructured":"Zarekiani, P. et al. The neurovascular unit in leukodystrophies: towards solving the puzzle. Fluids Barriers CNS 19, 18 (2022).","journal-title":"Fluids Barriers CNS"},{"key":"59042_CR13","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1111\/epi.17210","volume":"63","author":"EA van Vliet","year":"2022","unstructured":"van Vliet, E. A. & Marchi, N. Neurovascular unit dysfunction as a mechanism of seizures and epilepsy during aging. Epilepsia 63, 1297\u20131313 (2022).","journal-title":"Epilepsia"},{"key":"59042_CR14","doi-asserted-by":"publisher","first-page":"106028","DOI":"10.1016\/j.nbd.2023.106028","volume":"178","author":"JM Cashion","year":"2023","unstructured":"Cashion, J. M., Young, K. M. & Sutherland, B. A. How does neurovascular unit dysfunction contribute to multiple sclerosis? Neurobiol. Dis. 178, 106028 (2023).","journal-title":"Neurobiol. Dis."},{"key":"59042_CR15","doi-asserted-by":"publisher","first-page":"20230029","DOI":"10.1002\/EXP.20230029","volume":"4","author":"Y Dong","year":"2024","unstructured":"Dong, Y. et al. Cerebrospinal fluid efflux through dynamic paracellular pores on venules as a missing piece of the brain drainage system. Exploration 4, 20230029 (2024).","journal-title":"Exploration"},{"key":"59042_CR16","doi-asserted-by":"publisher","first-page":"2696","DOI":"10.1093\/brain\/awab148","volume":"144","author":"KT Thakur","year":"2021","unstructured":"Thakur, K. T. et al. COVID-19 neuropathology at Columbia University Irving Medical Center\/New York Presbyterian Hospital. Brain 144, 2696\u20132708 (2021).","journal-title":"Brain"},{"key":"59042_CR17","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/0022-510X(84)90156-4","volume":"63","author":"E Taskinen","year":"1984","unstructured":"Taskinen, E., Koskiniemi, M. L. & Vaheri, A. Herpes simplex virus encephalitis. Prolonged intrathecal IgG synthesis and cellular activity in the cerebrospinal fluid with transient impairment of blood-brain barrier. J. Neurol. Sci. 63, 331\u2013338 (1984).","journal-title":"J. Neurol. Sci."},{"key":"59042_CR18","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1046\/j.1365-2990.2000.00243.x","volume":"26","author":"A Lellouch-Tubiana","year":"2000","unstructured":"Lellouch-Tubiana, A. et al. Immunocytochemical characterization of long-term persistent immune activation in human brain after herpes simplex encephalitis. Neuropathol. Appl. Neurobiol. 26, 285\u2013294 (2000).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"59042_CR19","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1111\/j.1365-2990.1991.tb00737.x","volume":"17","author":"JA Nicoll","year":"1991","unstructured":"Nicoll, J. A., Maitland, N. J. & Love, S. Autopsy neuropathological findings in \u2018burnt out\u2019 herpes simplex encephalitis and use of the polymerase chain reaction to detect viral DNA. Neuropathol. Appl. Neurobiol. 17, 375\u2013382 (1991).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"59042_CR20","doi-asserted-by":"crossref","unstructured":"He, S. & Han, J. Manipulation of host cell death pathways by herpes simplex virus. Curr. Top. Microbiol. Immunol. 442, 85\u2013103 (2023).","DOI":"10.1007\/82_2020_196"},{"key":"59042_CR21","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1016\/j.vaccine.2013.08.066","volume":"32","author":"C Johnston","year":"2014","unstructured":"Johnston, C., Koelle, D. M. & Wald, A. Current status and prospects for development of an HSV vaccine. Vaccine 32, 1553\u20131560 (2014).","journal-title":"Vaccine"},{"key":"59042_CR22","doi-asserted-by":"publisher","first-page":"e1008899","DOI":"10.1371\/journal.ppat.1008899","volume":"16","author":"H Qiao","year":"2020","unstructured":"Qiao, H. et al. Herpes simplex virus type 1 infection leads to neurodevelopmental disorder-associated neuropathological changes. PLoS Pathog. 16, e1008899 (2020).","journal-title":"PLoS Pathog."},{"key":"59042_CR23","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1016\/j.stem.2021.03.004","volume":"28","author":"V Krenn","year":"2021","unstructured":"Krenn, V. et al. Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly. Cell Stem Cell 28, 1362\u20131379.e7 (2021).","journal-title":"Cell Stem Cell"},{"key":"59042_CR24","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1038\/s41564-023-01405-y","volume":"8","author":"A Rybak-Wolf","year":"2023","unstructured":"Rybak-Wolf, A. et al. Modelling viral encephalitis caused by herpes simplex virus 1 infection in cerebral organoids. Nat. Microbiol. 8, 1252\u20131266 (2023).","journal-title":"Nat. Microbiol."},{"key":"59042_CR25","doi-asserted-by":"crossref","unstructured":"Qiao, H. et al. Cerebral organoids for modeling of HSV-1-induced-amyloid \u03b2 associated neuropathology and phenotypic rescue. Int. J. Mol. Sci. 23, 5981 (2022).","DOI":"10.3390\/ijms23115981"},{"key":"59042_CR26","doi-asserted-by":"publisher","first-page":"3072","DOI":"10.1039\/D0LC90083D","volume":"20","author":"ML Shuler","year":"2020","unstructured":"Shuler, M. L. Organ-on-a-chip systems: translating concept into practice. Lab Chip 20, 3072\u20133073 (2020).","journal-title":"Lab Chip"},{"key":"59042_CR27","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/s41576-022-00466-9","volume":"23","author":"DE Ingber","year":"2022","unstructured":"Ingber, D. E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat. Rev. Genet. 23, 467\u2013491 (2022).","journal-title":"Nat. Rev. Genet."},{"key":"59042_CR28","doi-asserted-by":"publisher","first-page":"3550","DOI":"10.1021\/acs.accounts.1c00411","volume":"54","author":"Y Wang","year":"2021","unstructured":"Wang, Y., Wang, P. & Qin, J. Microfluidic organs-on-a-chip for modeling human infectious diseases. Acc. Chem. Res. 54, 3550\u20133562 (2021).","journal-title":"Acc. Chem. Res."},{"key":"59042_CR29","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1038\/s41551-021-00743-8","volume":"5","author":"J Kim","year":"2021","unstructured":"Kim, J. et al. Fungal brain infection modelled in a human-neurovascular-unit-on-a-chip with a functional blood-brain barrier. Nat. Biomed. Eng. 5, 830\u2013846 (2021).","journal-title":"Nat. Biomed. Eng."},{"key":"59042_CR30","doi-asserted-by":"crossref","unstructured":"Wang, P. et al. Blood-brain barrier injury and neuroinflammation induced by SARS-CoV-2 in a lung-brain microphysiological system. Nat. Biomed. Eng. 8, 1053\u20131068 (2024).","DOI":"10.1038\/s41551-023-01054-w"},{"key":"59042_CR31","doi-asserted-by":"crossref","unstructured":"Boghdeh, N. A. et al. Application of a human blood brain barrier organ-on-a-chip model to evaluate small molecule effectiveness against Venezuelan equine encephalitis virus. Viruses 14, 2799 (2022).","DOI":"10.3390\/v14122799"},{"key":"59042_CR32","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01233-23","volume":"11","author":"R Rauti","year":"2023","unstructured":"Rauti, R. et al. Insight on bacterial newborn meningitis using a neurovascular-unit-on-a-chip. Microbiol. Spectr. 11, e0123323 (2023).","journal-title":"Microbiol. Spectr."},{"key":"59042_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13896-7","volume":"11","author":"SI Ahn","year":"2020","unstructured":"Ahn, S. I. et al. Microengineered human blood-brain barrier platform for understanding nanoparticle transport mechanisms. Nat. Commun. 11, 175 (2020).","journal-title":"Nat. Commun."},{"key":"59042_CR34","doi-asserted-by":"publisher","first-page":"eaay8828","DOI":"10.1126\/sciadv.aay8828","volume":"6","author":"DM Cairns","year":"2020","unstructured":"Cairns, D. M. et al. A 3D human brain-like tissue model of herpes-induced Alzheimer\u2019s disease. Sci. Adv. 6, eaay8828 (2020).","journal-title":"Sci. Adv."},{"key":"59042_CR35","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.neulet.2007.09.077","volume":"429","author":"MA Wozniak","year":"2007","unstructured":"Wozniak, M. A. et al. Herpes simplex virus infection causes cellular \u03b2-amyloid accumulation and secretase upregulation. Neurosci. Lett. 429, 95\u2013100 (2007).","journal-title":"Neurosci. Lett."},{"key":"59042_CR36","doi-asserted-by":"publisher","first-page":"20220160","DOI":"10.1002\/EXP.20220160","volume":"3","author":"W Zhang","year":"2023","unstructured":"Zhang, W. et al. Microglial targeted therapy relieves cognitive impairment caused by Cntnap4 deficiency. Exploration 3, 20220160 (2023).","journal-title":"Exploration"},{"key":"59042_CR37","doi-asserted-by":"publisher","first-page":"6709","DOI":"10.1007\/s12035-015-9593-4","volume":"53","author":"L Xu","year":"2016","unstructured":"Xu, L., He, D. & Bai, Y. Microglia-mediated inflammation and neurodegenerative disease. Mol. Neurobiol. 53, 6709\u20136715 (2016).","journal-title":"Mol. Neurobiol."},{"key":"59042_CR38","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1016\/j.immuni.2021.09.014","volume":"54","author":"K Borst","year":"2021","unstructured":"Borst, K., Dumas, A. A. & Prinz, M. Microglia: immune and non-immune functions. Immunity 54, 2194\u20132208 (2021).","journal-title":"Immunity"},{"key":"59042_CR39","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1111\/cns.13899","volume":"28","author":"F Yu","year":"2022","unstructured":"Yu, F. et al. Phagocytic microglia and macrophages in brain injury and repair. CNS Neurosci. Ther. 28, 1279\u20131293 (2022).","journal-title":"CNS Neurosci. Ther."},{"key":"59042_CR40","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.4049\/jimmunol.176.2.1046","volume":"176","author":"PK Mander","year":"2006","unstructured":"Mander, P. K., Jekabsone, A. & Brown, G. C. Microglia proliferation is regulated by hydrogen peroxide from NADPH oxidase. J. Immunol. 176, 1046\u20131052 (2006).","journal-title":"J. Immunol."},{"key":"59042_CR41","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1002\/jnr.490330205","volume":"33","author":"S Ganter","year":"1992","unstructured":"Ganter, S. et al. Growth control of cultured microglia. J. Neurosci. Res. 33, 218\u2013230 (1992).","journal-title":"J. Neurosci. Res."},{"key":"59042_CR42","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1089\/089771502320914723","volume":"19","author":"JM Vela","year":"2002","unstructured":"Vela, J. M. et al. Time course of proliferation and elimination of microglia\/macrophages in different neurodegenerative conditions. J. Neurotrauma 19, 1503\u20131520 (2002).","journal-title":"J. Neurotrauma"},{"key":"59042_CR43","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1007\/s12035-013-8620-6","volume":"49","author":"R Fu","year":"2014","unstructured":"Fu, R. et al. Phagocytosis of microglia in the central nervous system diseases. Mol. Neurobiol. 49, 1422\u20131434 (2014).","journal-title":"Mol. Neurobiol."},{"key":"59042_CR44","doi-asserted-by":"publisher","first-page":"13005","DOI":"10.1128\/JVI.01994-14","volume":"88","author":"ED Quick","year":"2014","unstructured":"Quick, E. D. et al. Activation of intrinsic immune responses and microglial phagocytosis in an ex vivo spinal cord slice culture model of West Nile virus infection. J. Virol. 88, 13005\u201313014 (2014).","journal-title":"J. Virol."},{"key":"59042_CR45","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1089\/ars.2010.3488","volume":"14","author":"N Hariharan","year":"2011","unstructured":"Hariharan, N., Zhai, P. & Sadoshima, J. Oxidative stress stimulates autophagic flux during ischemia\/reperfusion. Antioxid. Redox Signal 14, 2179\u20132190 (2011).","journal-title":"Antioxid. Redox Signal"},{"key":"59042_CR46","doi-asserted-by":"crossref","unstructured":"Yan, Y. et al. Jatrophane diterpenoids from Euphorbia peplus Linn. as activators of autophagy and inhibitors of tau pathology. Int. J. Mol. Sci. 24, 1088 (2023).","DOI":"10.3390\/ijms24021088"},{"key":"59042_CR47","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1039\/D2OB01965E","volume":"21","author":"Y Yan","year":"2023","unstructured":"Yan, Y. et al. Munronin V with 7\/7\/6 tricarbocyclic framework from Munronia henryi harms inhibits tau pathology by activating autophagy. Org. Biomol. Chem. 21, 514\u2013519 (2023).","journal-title":"Org. Biomol. Chem."},{"key":"59042_CR48","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202350384","volume":"53","author":"Q Zhao","year":"2023","unstructured":"Zhao, Q. et al. Ubiquitination network in the type I IFN-induced antiviral signaling pathway. Eur. J. Immunol. 53, e2350384 (2023).","journal-title":"Eur. J. Immunol."},{"key":"59042_CR49","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nri3787","volume":"15","author":"F McNab","year":"2015","unstructured":"McNab, F. et al. Type I interferons in infectious disease. Nat. Rev. Immunol. 15, 87\u2013103 (2015).","journal-title":"Nat. Rev. Immunol."},{"key":"59042_CR50","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3389\/fcimb.2019.00127","volume":"9","author":"EI Tognarelli","year":"2019","unstructured":"Tognarelli, E. I. et al. Herpes simplex virus evasion of early host antiviral responses. Front. Cell Infect. Microbiol. 9, 127 (2019).","journal-title":"Front. Cell Infect. Microbiol."},{"key":"59042_CR51","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.molimm.2021.03.027","volume":"135","author":"L Zhang","year":"2021","unstructured":"Zhang, L. et al. HSV-1-encoded ICP0 degrades the host deubiquitinase BRCC36 to antagonize interferon antiviral response. Mol. Immunol. 135, 28\u201335 (2021).","journal-title":"Mol. Immunol."},{"key":"59042_CR52","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.virol.2008.01.001","volume":"374","author":"KE Johnson","year":"2008","unstructured":"Johnson, K. E., Song, B. & Knipe, D. M. Role for herpes simplex virus 1 ICP27 in the inhibition of type I interferon signaling. Virology 374, 487\u2013494 (2008).","journal-title":"Virology"},{"key":"59042_CR53","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1007\/s13365-016-0440-9","volume":"22","author":"Y Tsalenchuck","year":"2016","unstructured":"Tsalenchuck, Y., Steiner, I. & Panet, A. Innate defense mechanisms against HSV-1 infection in the target tissues, skin and brain. J. Neurovirol. 22, 641\u2013649 (2016).","journal-title":"J. Neurovirol."},{"key":"59042_CR54","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.chom.2009.05.016","volume":"5","author":"V Deretic","year":"2009","unstructured":"Deretic, V. & Levine, B. Autophagy, immunity, and microbial adaptations. Cell Host Microbe 5, 527\u2013549 (2009).","journal-title":"Cell Host Microbe"},{"key":"59042_CR55","doi-asserted-by":"publisher","first-page":"314","DOI":"10.3390\/v2010314","volume":"2","author":"Y Cavignac","year":"2010","unstructured":"Cavignac, Y. & Esclatine, A. Herpesviruses and autophagy: catch me if you can! Viruses 2, 314\u2013333 (2010).","journal-title":"Viruses"},{"key":"59042_CR56","doi-asserted-by":"publisher","first-page":"e00267","DOI":"10.1128\/mBio.00267-12","volume":"3","author":"PA Gobeil","year":"2012","unstructured":"Gobeil, P. A. & Leib, D. A. Herpes simplex virus \u03b334.5 interferes with autophagosome maturation and antigen presentation in dendritic cells. mBio 3, e00267\u201312 (2012).","journal-title":"mBio"},{"key":"59042_CR57","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.chom.2006.12.001","volume":"1","author":"A Orvedahl","year":"2007","unstructured":"Orvedahl, A. et al. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1, 23\u201335 (2007).","journal-title":"Cell Host Microbe"},{"key":"59042_CR58","doi-asserted-by":"publisher","first-page":"24","DOI":"10.4161\/auto.2176","volume":"2","author":"Z Talloczy","year":"2006","unstructured":"Talloczy, Z., Virgin, H. W. T. & Levine, B. PKR-dependent autophagic degradation of herpes simplex virus type 1. Autophagy 2, 24\u201329 (2006).","journal-title":"Autophagy"},{"key":"59042_CR59","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1073\/pnas.94.3.843","volume":"94","author":"B He","year":"1997","unstructured":"He, B., Gross, M. & Roizman, B. The \u03b3134.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1\u03b1 to dephosphorylate the \u03b1 subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc. Natl Acad. Sci. USA 94, 843\u2013848 (1997).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"59042_CR60","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1080\/15548627.2016.1139262","volume":"12","author":"D O\u2019Connell","year":"2016","unstructured":"O\u2019Connell, D. & Liang, C. Autophagy interaction with herpes simplex virus type-1 infection. Autophagy 12, 451\u2013459 (2016).","journal-title":"Autophagy"},{"key":"59042_CR61","doi-asserted-by":"publisher","first-page":"12128","DOI":"10.1128\/JVI.01356-07","volume":"81","author":"DE Alexander","year":"2007","unstructured":"Alexander, D. E. et al. Analysis of the role of autophagy in replication of herpes simplex virus in cell culture. J. Virol. 81, 12128\u201312134 (2007).","journal-title":"J. Virol."},{"key":"59042_CR62","doi-asserted-by":"publisher","first-page":"4212","DOI":"10.1128\/JVI.02435-10","volume":"85","author":"S McFarlane","year":"2011","unstructured":"McFarlane, S. et al. Early induction of autophagy in human fibroblasts after infection with human cytomegalovirus or herpes simplex virus 1. J. Virol. 85, 4212\u20134221 (2011).","journal-title":"J. Virol."},{"key":"59042_CR63","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.micinf.2013.04.012","volume":"15","author":"G Tovilovic","year":"2013","unstructured":"Tovilovic, G. et al. mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells. Microbes Infect. 15, 615\u2013624 (2013).","journal-title":"Microbes Infect."},{"key":"59042_CR64","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1007\/s12038-014-9443-y","volume":"39","author":"G Petrovski","year":"2014","unstructured":"Petrovski, G. et al. Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells. J. Biosci. 39, 683\u2013692 (2014).","journal-title":"J. Biosci."},{"key":"59042_CR65","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.chom.2012.07.013","volume":"12","author":"B Yordy","year":"2012","unstructured":"Yordy, B. et al. A neuron-specific role for autophagy in antiviral defense against herpes simplex virus. Cell Host Microbe 12, 334\u2013345 (2012).","journal-title":"Cell Host Microbe"},{"key":"59042_CR66","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/cne.21974","volume":"513","author":"FA Azevedo","year":"2009","unstructured":"Azevedo, F. A. et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J. Comp. Neurol. 513, 532\u2013541 (2009).","journal-title":"J. Comp. Neurol."},{"key":"59042_CR67","doi-asserted-by":"publisher","first-page":"3865","DOI":"10.1002\/cne.24040","volume":"524","author":"CS von Bartheld","year":"2016","unstructured":"von Bartheld, C. S., Bahney, J. & Herculano-Houzel, S. The search for true numbers of neurons and glial cells in the human brain: a review of 150 years of cell counting. J. Comp. Neurol. 524, 3865\u20133895 (2016).","journal-title":"J. Comp. Neurol."},{"key":"59042_CR68","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1002\/glia.22683","volume":"62","author":"S Herculano-Houzel","year":"2014","unstructured":"Herculano-Houzel, S. The glia\/neuron ratio: how it varies uniformly across brain structures and species and what that means for brain physiology and evolution. Glia 62, 1377\u20131391 (2014).","journal-title":"Glia"},{"key":"59042_CR69","doi-asserted-by":"publisher","first-page":"1329540","DOI":"10.3389\/fimmu.2023.1329540","volume":"14","author":"S Sun","year":"2023","unstructured":"Sun, S. et al. Case report: Overlapping anti-AMPAR encephalitis with anti-IgLON5 disease post herpes simplex virus encephalitis. Front. Immunol. 14, 1329540 (2023).","journal-title":"Front. Immunol."},{"key":"59042_CR70","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.genhosppsych.2006.05.004","volume":"28","author":"C Fazekas","year":"2006","unstructured":"Fazekas, C. et al. Depressive symptoms following herpes simplex encephalitis\u2014an underestimated phenomenon? Gen. Hosp. Psychiatry 28, 403\u2013407 (2006).","journal-title":"Gen. Hosp. Psychiatry"},{"key":"59042_CR71","doi-asserted-by":"publisher","first-page":"114501","DOI":"10.1016\/j.expneurol.2023.114501","volume":"368","author":"ACP Campos","year":"2023","unstructured":"Campos, A. C. P. et al. What do we know about astrocytes and the antidepressant effects of DBS? Exp. Neurol. 368, 114501 (2023).","journal-title":"Exp. Neurol."},{"key":"59042_CR72","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1113\/JP270988","volume":"595","author":"E Blanco-Suarez","year":"2017","unstructured":"Blanco-Suarez, E., Caldwell, A. L. & Allen, N. J. Role of astrocyte-synapse interactions in CNS disorders. J. Physiol. 595, 1903\u20131916 (2017).","journal-title":"J. Physiol."},{"key":"59042_CR73","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-43214-7","volume":"13","author":"CT Bolden","year":"2023","unstructured":"Bolden, C. T. et al. Validation and characterization of a novel blood-brain barrier platform for investigating traumatic brain injury. Sci. Rep. 13, 16150 (2023).","journal-title":"Sci. Rep."},{"key":"59042_CR74","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1038\/s41591-020-0886-4","volume":"26","author":"JW Blanchard","year":"2020","unstructured":"Blanchard, J. W. et al. Reconstruction of the human blood-brain barrier in vitro reveals a pathogenic mechanism of APOE4 in pericytes. Nat. Med. 26, 952\u2013963 (2020).","journal-title":"Nat. Med."},{"key":"59042_CR75","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/s41578-020-0199-8","volume":"5","author":"EA Aisenbrey","year":"2020","unstructured":"Aisenbrey, E. A. & Murphy, W. L. Synthetic alternatives to Matrigel. Nat. Rev. Mater. 5, 539\u2013551 (2020).","journal-title":"Nat. Rev. Mater."},{"key":"59042_CR76","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1136\/svn-2018-000198","volume":"4","author":"L Xu","year":"2019","unstructured":"Xu, L., Nirwane, A. & Yao, Y. Basement membrane and blood-brain barrier. Stroke Vasc. Neurol. 4, 78\u201382 (2019).","journal-title":"Stroke Vasc. Neurol."},{"key":"59042_CR77","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1039\/c000022a","volume":"10","author":"T Liu","year":"2010","unstructured":"Liu, T., Lin, B. & Qin, J. Carcinoma-associated fibroblasts promoted tumor spheroid invasion on a microfluidic 3D co-culture device. Lab Chip 10, 1671\u20131677 (2010).","journal-title":"Lab Chip"},{"key":"59042_CR78","doi-asserted-by":"crossref","unstructured":"Wang, P. et al. Malignant melanoma-derived exosomes induce endothelial damage and glial activation on a human BBB chip model. Biosensors 12, 89 (2022).","DOI":"10.3390\/bios12020089"},{"key":"59042_CR79","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/j.tibtech.2019.04.006","volume":"37","author":"A Oddo","year":"2019","unstructured":"Oddo, A. et al. Advances in microfluidic blood-brain barrier (BBB) models. Trends Biotechnol. 37, 1295\u20131314 (2019).","journal-title":"Trends Biotechnol."},{"key":"59042_CR80","doi-asserted-by":"publisher","first-page":"104882","DOI":"10.1016\/j.antiviral.2020.104882","volume":"181","author":"C Conzelmann","year":"2020","unstructured":"Conzelmann, C. et al. An enzyme-based immunodetection assay to quantify SARS-CoV-2 infection. Antivir. Res. 181, 104882 (2020).","journal-title":"Antivir. Res."},{"key":"59042_CR81","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","volume":"162","author":"P Chomczynski","year":"1987","unstructured":"Chomczynski, P. & Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162, 156\u2013159 (1987).","journal-title":"Anal. Biochem."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59042-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59042-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59042-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T10:02:55Z","timestamp":1744970575000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59042-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,18]]},"references-count":81,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["59042"],"URL":"https:\/\/doi.org\/10.1038\/s41467-025-59042-4","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,18]]},"assertion":[{"value":"16 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3701"}}