{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T01:35:24Z","timestamp":1782437724097,"version":"3.54.5"},"reference-count":64,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Institute for Agriculture, Food and Environment","award":["no grant number"],"award-info":[{"award-number":["no grant number"]}]},{"name":"DIMMalInf","award":["no grant number"],"award-info":[{"award-number":["no grant number"]}]},{"name":"DIM1Health","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, Flavivirus genus, is responsible for neurological symptoms that may cause permanent disability or death. With an incidence on the rise, it is the major arbovirus affecting humans in Central\/Northern Europe and North-Eastern Asia. Neuronal death is a critical feature of TBEV infection, yet little is known about the type of death and the molecular mechanisms involved. In this study, we used a recently established pathological model of TBEV infection based on human neuronal\/glial cells differentiated from fetal neural progenitors and transcriptomic approaches to tackle this question. We confirmed the occurrence of apoptotic death in these cultures and further showed that genes involved in pyroptotic death were up-regulated, suggesting that this type of death also occurs in TBEV-infected human brain cells. On the contrary, no up-regulation of major autophagic genes was found. Furthermore, we demonstrated an up-regulation of a cluster of genes belonging to the extrinsic apoptotic pathway and revealed the cellular types expressing them. Our results suggest that neuronal death occurs by multiple mechanisms in TBEV-infected human neuronal\/glial cells, thus providing a first insight into the molecular pathways that may be involved in neuronal death when the human brain is infected by TBEV.<\/jats:p>","DOI":"10.3390\/v13112255","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T23:07:21Z","timestamp":1636672041000},"page":"2255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Transcriptomic Studies Suggest a Coincident Role for Apoptosis and Pyroptosis but Not for Autophagic Neuronal Death in TBEV-Infected Human Neuronal\/Glial Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6003-9244","authenticated-orcid":false,"given":"Mazigh","family":"Fares","sequence":"first","affiliation":[{"name":"UMR1161 Virologie, Anses, INRAE, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris-Est, F-94700 Maisons-Alfort, France"},{"name":"MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Gorna","sequence":"additional","affiliation":[{"name":"UMR1161 Virologie, Anses, INRAE, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris-Est, F-94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mie","family":"Berry","sequence":"additional","affiliation":[{"name":"UMR1161 Virologie, Anses, INRAE, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris-Est, F-94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Cochet-Bernoin","sequence":"additional","affiliation":[{"name":"UMR1161 Virologie, Anses, INRAE, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris-Est, F-94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Piumi","sequence":"additional","affiliation":[{"name":"UMR1161 Virologie, Anses, INRAE, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris-Est, F-94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8275-8741","authenticated-orcid":false,"given":"Odile","family":"Blanchet","sequence":"additional","affiliation":[{"name":"CHU Angers, Centre de Ressources Biologiques, BB-0033-00038 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Haddad","sequence":"additional","affiliation":[{"name":"UMR BIPAR 956, Anses, INRAE, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris-Est, F-94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Richardson","sequence":"additional","affiliation":[{"name":"UMR1161 Virologie, Anses, INRAE, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris-Est, F-94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Coulpier","sequence":"additional","affiliation":[{"name":"UMR1161 Virologie, Anses, INRAE, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris-Est, F-94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Beaut\u00e9, J., Spiteri, G., Warns-Petit, E., and Zeller, H. (2018). Tick-borne encephalitis in Europe, 2012 to 2016. Eurosurveillance, 23.","DOI":"10.2807\/1560-7917.ES.2018.23.45.1800201"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mantke, O.D., Escadafal, C., Niedrig, M., Pfeffer, M., and collective on behalf of the Working Group for Tick-Borne Encephalitis Virus (2011). Tick-borne encephalitis in Europe, 2007 to 2009. Eurosurveillance, 16.","DOI":"10.2807\/ese.16.39.19976-en"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Borde, J.P., Kaier, K., Hehn, P., Matzarakis, A., Frey, S., Bestehorn, M., Dobler, G., and Chitimia-Dobler, L. (2021). The complex interplay of climate, TBEV vector dynamics and TBEV infection rates in ticks\u2014Monitoring a natural TBEV focus in Germany, 2009\u20132018. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0244668"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.antiviral.2019.01.014","article-title":"Tick-borne encephalitis in Europe and Russia: Review of pathogenesis, clinical features, therapy, and vaccines","volume":"164","author":"Ruzek","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.jviromet.2009.10.003","article-title":"Tick-borne encephalitis outbreak in Hungary due to consumption of raw goat milk","volume":"163","author":"Balogh","year":"2010","journal-title":"J. Virol. Methods"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Brockmann, S., Oehme, R., Buckenmaier, T., Beer, M., Jeffery-Smith, A., Spannenkrebs, M., Haag-Milz, S., Wagner-Wiening, C., Schlegel, C., and Fritz, J. (2018). A cluster of two human cases of tick-borne encephalitis (TBE) transmitted by unpasteurised goat milk and cheese in Germany, May 2016. Eurosurveillance, 23.","DOI":"10.2807\/1560-7917.ES.2018.23.15.17-00336"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.21101\/cejph.a5272","article-title":"Milk outbreaks of tick-borne encephalitis in Slovakia, 2012-2016","volume":"26","author":"Dorko","year":"2018","journal-title":"Cent. Eur. J. Public Health"},{"key":"ref_8","first-page":"1","article-title":"Changes in cytokine and chemokine profiles in mouse serum and brain, and in human neural cells, upon tick-borne encephalitis virus infection","volume":"16","author":"Formanova","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1080\/13550280600848746","article-title":"Inflammatory response in human tick-borne encephalitis: Analysis of postmortem brain tissue","volume":"12","author":"Gelpi","year":"2006","journal-title":"J. NeuroVirol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1093\/jnen\/64.6.506","article-title":"Visualization of Central European Tick-Borne Encephalitis Infection in Fatal Human Cases","volume":"64","author":"Gelpi","year":"2005","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.virol.2009.04.026","article-title":"Mortality following peripheral infection with Tick-borne encephalitis virus results from a combination of central nervous system pathology, systemic inflammatory and stress responses","volume":"390","author":"Hayasaka","year":"2009","journal-title":"Virology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2008.11.023","article-title":"CD8+ T-cells mediate immunopathology in tick-borne encephalitis","volume":"384","author":"Palus","year":"2009","journal-title":"Virology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1152\/physrev.00011.2017","article-title":"Neuronal Cell Death","volume":"98","author":"Fricker","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0197-0186(02)00194-8","article-title":"Spatial resolution of phospholipid scramblase 1 (PLSCR1), caspase-3 activation and DNA-fragmentation in the human hippocampus after cerebral ischemia","volume":"43","author":"Rami","year":"2003","journal-title":"Neurochem. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1582-4934.2001.tb00134.x","article-title":"Cell death mechanisms in neurodegeneration","volume":"5","author":"Jellinger","year":"2001","journal-title":"J. Cell. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/S0002-9440(10)65460-0","article-title":"Activation of Caspase-3 in Single Neurons and Autophagic Granules of Granulovacuolar Degeneration in Alzheimer\u2019s Disease: Evidence for Apoptotic Cell Death","volume":"155","author":"Stadelmann","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/sj.cdd.4400921","article-title":"Formation of the Apaf-1\/cytochrome c complex precedes activation of caspase-9 during seizure-induced neuronal death","volume":"8","author":"Henshall","year":"2001","journal-title":"Cell Death Differ."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0169-328X(01)00058-4","article-title":"Caspase mRNA expression in a rat model of focal cerebral ischemia","volume":"89","author":"Harrison","year":"2001","journal-title":"Mol. Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1099\/vir.0.19447-0","article-title":"The mechanism of cell death during West Nile virus infection is dependent on initial infectious dose","volume":"84","author":"Chu","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/ana.24968","article-title":"Differential neuronal susceptibility and apoptosis in congenital Zika virus infection","volume":"82","author":"Ho","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_21","first-page":"182","article-title":"Apoptosis as a mechanism for the cytopathic action of tick-borne encephalitis virus","volume":"43","author":"Isaeva","year":"1998","journal-title":"Vopr. Virusol."},{"key":"ref_22","first-page":"54","article-title":"The morphological characteristics of cell death in different forms of acute tick-borne encephalitis","volume":"114","author":"Kamalov","year":"1998","journal-title":"Morfology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1099\/vir.0.010058-0","article-title":"Morphological changes in human neural cells following tick-borne encephalitis virus infection","volume":"90","author":"Ruzek","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-020-01756-x","article-title":"Pathological modeling of TBEV infection reveals differential innate immune responses in human neurons and astrocytes that correlate with their susceptibility to infection","volume":"17","author":"Fares","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tins.2019.11.005","article-title":"Fiery Cell Death: Pyroptosis in the Central Nervous System","volume":"43","author":"McKenzie","year":"2020","journal-title":"Trends Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-014-0233-0","article-title":"NLRP1 inflammasome is activated in patients with medial temporal lobe epilepsy and contributes to neuronal pyroptosis in amygdala kindling-induced rat model","volume":"12","author":"Tan","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tan, M.-S., Tan, L., Jiang, T., Zhu, X.-C., Wang, H.-F., Jia, C.-D., and Yu, J.-T. (2014). Amyloid-\u03b2 induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer\u2019s disease. Cell Death Dis., 5.","DOI":"10.1038\/cddis.2014.348"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lim, S.M., Ham, H.-J.V.D., Oduber, M., Martina, E., Zaaraoui-Boutahar, F., Roose, J.M., van Ijcken, W., Osterhaus, A.D.M.E., Andeweg, A.C., and Koraka, P. (2017). Transcriptomic Analyses Reveal Differential Gene Expression of Immune and Cell Death Pathways in the Brains of Mice Infected with West Nile Virus and Chikungunya Virus. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01556"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1016\/j.vaccine.2018.04.002","article-title":"Inhibition of caspase-1 prolongs survival of mice infected with rabies virus","volume":"37","author":"Koraka","year":"2019","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.bbrc.2020.11.023","article-title":"Zika virus protease induces caspase-independent pyroptotic cell death by directly cleaving gasdermin D","volume":"534","author":"Yamaoka","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1042\/BST0360786","article-title":"Life, death and burial: Multifaceted impact of autophagy","volume":"36","author":"Galluzzi","year":"2008","journal-title":"Biochem. Soc. Trans."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1099\/vir.0.007914-0","article-title":"A role for autophagolysosomes in dengue virus 3 production in HepG2 cells","volume":"90","author":"Khakpoor","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"434","DOI":"10.4161\/auto.5.3.7925","article-title":"Linking dengue virus entry and translation\/replication through amphisomes","volume":"5","author":"Panyasrivanit","year":"2009","journal-title":"Autophagy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.virusres.2014.07.016","article-title":"Autophagy inhibits viral genome replication and gene expression stages in West Nile virus infection","volume":"191","author":"Kobayashi","year":"2014","journal-title":"Virus Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.virusres.2017.09.006","article-title":"Role of autophagy in Zika virus infection and pathogenesis","volume":"254","author":"Chiramel","year":"2018","journal-title":"Virus Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bily, T., Palus, M., Eyer, L., Elsterov\u00e1, J., Vancov\u00e1, M., and R\u016f\u017eek, D. (2015). Electron Tomography Analysis of Tick-Borne Encephalitis Virus Infection in Human Neurons. Sci. Rep., 5.","DOI":"10.1038\/srep10745"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1128\/JVI.05663-11","article-title":"Borna Disease Virus Infects Human Neural Progenitor Cells and Impairs Neurogenesis","volume":"86","author":"Brnic","year":"2011","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Scordel, C., Huttin, A., Cochet-Bernoin, M., Szelechowski, M., Poulet, A., Richardson, J., Benchoua, A., Gonzalez-Dunia, D., Eloit, M., and Coulpier, M. (2015). Borna Disease Virus Phosphoprotein Impairs the Developmental Program Controlling Neurogenesis and Reduces Human GABAergic Neurogenesis. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004859"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1099\/0022-1317-77-5-1035","article-title":"Characterization and complete genome sequences of high- and low-virulence variants of tick-borne encephalitis virus","volume":"77","author":"Wallner","year":"1996","journal-title":"J. Gen. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/00001756-199512000-00014","article-title":"A Cautionary Note on the Use of the TUNEL Stain to Determine Apoptosis","volume":"7","year":"1995","journal-title":"Neuroreport"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/imr.12287","article-title":"Pyroptotic cell death defends against intracellular pathogens","volume":"265","author":"Jorgensen","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/imr.12534","article-title":"Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases","volume":"277","author":"Man","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.virol.2005.08.043","article-title":"Host cell killing by the West Nile Virus NS2B\u2013NS3 proteolytic complex: NS3 alone is sufficient to recruit caspase-8-based apoptotic pathway","volume":"345","author":"Ramanathan","year":"2006","journal-title":"Virology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0014-5793(01)02573-X","article-title":"West Nile virus-induced bax-dependent apoptosis","volume":"500","author":"Parquet","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.neuroscience.2015.06.038","article-title":"TNF and its receptors in the CNS: The essential, the desirable and the deleterious effects","volume":"302","author":"Probert","year":"2015","journal-title":"Neuroscience"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1161\/01.STR.28.6.1233","article-title":"Tumor Necrosis Factor-\u03b1","volume":"28","author":"Barone","year":"1997","journal-title":"Stroke"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/jnr.1059","article-title":"TNF-alpha stimulates caspase-3 activation and apoptotic cell death in primary septo-hippocampal cultures","volume":"64","author":"Zhao","year":"2001","journal-title":"J. Neurosci. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jneuroim.2010.05.003","article-title":"TNF-\u03b1-dependent regulation of CXCR3 expression modulates neuronal survival during West Nile virus encephalitis","volume":"224","author":"Zhang","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kumar, M., Verma, S., and Nerurkar, V.R. (2010). Pro-inflammatory cytokines derived from West Nile virus (WNV)-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death. J. Neuroinflamm., 7.","DOI":"10.1186\/1742-2094-7-73"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jneuroim.2005.06.027","article-title":"Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate","volume":"167","author":"Roth","year":"2005","journal-title":"J. Neuroimmunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S0140-6736(00)02659-3","article-title":"Human brain-cell death induced by tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL)","volume":"356","author":"Nitsch","year":"2000","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.neuron.2005.03.018","article-title":"Neuronal Damage in Autoimmune Neuroinflammation Mediated by the Death Ligand TRAIL","volume":"46","author":"Aktas","year":"2005","journal-title":"Neuron"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9430","DOI":"10.1074\/jbc.M113.512350","article-title":"Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Signaling and Cell Death in the Immature Central Nervous System after Hypoxia-Ischemia and Inflammation","volume":"289","author":"Kichev","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/BF03033825","article-title":"The signaling and apoptotic effects of TNF-related apoptosis-inducing ligand in HIV-1 associated dementia","volume":"8","author":"Huang","year":"2005","journal-title":"Neurotox. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.neuron.2005.04.028","article-title":"Taking Two TRAILS","volume":"46","author":"Ransohoff","year":"2005","journal-title":"Neuron"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2174\/156720511794604543","article-title":"Astrocytes: Implications for neuroinflammatory pathogenesis of Alzheimer\u2019s disease","volume":"8","author":"Li","year":"2011","journal-title":"Curr. Alzheimer Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Bian, P., Zheng, X., Wei, L., Ye, C., Fan, H., Cai, Y., Zhang, Y., Zhang, F., Jia, Z., and Lei, Y. (2017). MLKL Mediated Necroptosis Accelerates JEV-Induced Neuroinflammation in Mice. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00303"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Downs, K.P., Nguyen, H., Dorfleutner, A., and Stehlik, C. (2020). An overview of the non-canonical inflammasome. Mol. Asp. Med., 76.","DOI":"10.1016\/j.mam.2020.100924"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"23869","DOI":"10.1073\/pnas.2007773117","article-title":"Neural progenitor cell pyroptosis contributes to Zika virus-induced brain atrophy and represents a therapeutic target","volume":"117","author":"He","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.cyto.2018.08.008","article-title":"In situ inflammasome activation results in severe damage to the central nervous system in fatal Zika virus microcephaly cases","volume":"111","author":"Azevedo","year":"2018","journal-title":"Cytokine"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/imr.12541","article-title":"Caspase-8: Regulating life and death","volume":"277","author":"Tummers","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/nrm2529","article-title":"Autophagic cell death: The story of a misnomer","volume":"9","author":"Kroemer","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"783","DOI":"10.4269\/ajtmh.18-0761","article-title":"Significance of Autophagy in Dengue Virus Infection: A Brief Review","volume":"100","author":"Acharya","year":"2019","journal-title":"Am. J. Trop. Med. Hyg."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/11\/2255\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:28:17Z","timestamp":1760167697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/11\/2255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,10]]},"references-count":64,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["v13112255"],"URL":"https:\/\/doi.org\/10.3390\/v13112255","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,10]]}}}