{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T19:31:03Z","timestamp":1785007863501,"version":"3.55.0"},"reference-count":102,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pathogens"],"abstract":"<jats:p>The mechanisms by which SARS-CoV-2 infection lead to neuroinflammation and cognitive impairment in COVID-19 and Long COVID are unclear. Cerebrovascular Wnt\/\u03b2-catenin pathway activity is suppressed in association with neuroinflammation and cognitive impairment in a mouse model of COVID-19. In this study, we asked whether SARS-CoV-2 (NY Iota strain) infection of astrocytes would result in cell-autonomous changes in Wnt\/\u03b2-catenin pathway components. We report that induced pluripotent stem cell (hiPSC)-derived human astrocytes (iAs) are susceptible to sustained infection with SARS-CoV-2 in vitro. Real-time PCR revealed that SARS-CoV-2 infection of iAs decreased transcripts for Wnt3a, Wnt10b, and the downstream pathway effectors \u03b2-catenin and TCF3. Wnt7b was increased, as was the proinflammatory chemokine CXCL10. No changes were noted in Wnt3, Wnt7a, TCF1, TCF4, or LEF1. These data indicate that SARS-CoV-2 infection differentially influences Wnt\/\u03b2-catenin pathway components in astrocytes. These data could have implications for the mechanistic basis of COVID-19 and Long COVID.<\/jats:p>","DOI":"10.3390\/pathogens14100994","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T09:38:08Z","timestamp":1759397888000},"page":"994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["SARS-CoV-2 Infection Influences Wnt\/\u03b2-Catenin Pathway Components in Astrocytes"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6110-4450","authenticated-orcid":false,"given":"KaReisha F.","family":"Robinson","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avantika I.","family":"Ahiya","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5344-118X","authenticated-orcid":false,"given":"Justin M.","family":"Richner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6388-753X","authenticated-orcid":false,"given":"Sarah E.","family":"Lutz","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e0230822","DOI":"10.1128\/mbio.02308-22","article-title":"Neuropilin-1 Mediates SARS-CoV-2 Infection of Astrocytes in Brain Organoids, Inducing Inflammation Leading to Dysfunction and Death of Neurons","volume":"13","author":"Kong","year":"2022","journal-title":"mBio"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.omtm.2022.09.007","article-title":"SARS-CoV-2 infection increases the gene expression profile for Alzheimer\u2019s disease risk","volume":"27","author":"Green","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1038\/s41467-022-29440-z","article-title":"Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates","volume":"13","author":"Rutkai","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S2215-0366(21)00084-5","article-title":"6-month neurological and psychiatric outcomes in 236\u2009379 survivors of COVID-19: A retrospective cohort study using electronic health records","volume":"8","author":"Taquet","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6571","DOI":"10.1038\/s41467-021-26513-3","article-title":"Burdens of post-acute sequelae of COVID-19 by severity of acute infection, demographics and health status","volume":"12","author":"Xie","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41579-022-00846-2","article-title":"Long COVID: Major findings, mechanisms and recommendations","volume":"21","author":"Davis","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/s41586-022-05542-y","article-title":"SARS-CoV-2 infection and persistence in the human body and brain at autopsy","volume":"612","author":"Stein","year":"2022","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S1474-4422(20)30308-2","article-title":"Neuropathology of patients with COVID-19 in Germany: A post-mortem case series","volume":"19","author":"Matschke","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s00401-024-02743-9","article-title":"Neuropathological findings in Down syndrome, Alzheimer\u2019s disease and control patients with and without SARS-CoV-2: Preliminary findings","volume":"147","author":"Granholm","year":"2024","journal-title":"Acta Neuropathol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Motta, C.S., Torices, S., da Rosa, B.G., Marcos, A.C., Alvarez-Rosa, L., Siqueira, M., Moreno-Rodriguez, T., Matos, A.D.R., Caetano, B.C., and Martins, J. (2023). Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF-\u03baB Non-Canonical Pathway and Mitochondrial Remodeling. Viruses, 15.","DOI":"10.3390\/v15030745"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2122236119","DOI":"10.1073\/pnas.2122236119","article-title":"Tropism of SARS-CoV-2 for human cortical astrocytes","volume":"119","author":"Andrews","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1093\/brain\/awab148","article-title":"COVID-19 neuropathology at Columbia University Irving Medical Center\/New York Presbyterian Hospital","volume":"144","author":"Thakur","year":"2021","journal-title":"Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2200960119","DOI":"10.1073\/pnas.2200960119","article-title":"Morphological, cellular and molecular basis of brain infection in COVID-19 patients","volume":"119","author":"Crunfli","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1016\/j.neuron.2022.11.007","article-title":"Anatomical barriers against SARS-CoV-2 neuroinvasion at vulnerable interfaces visualized in deceased COVID-19 patients","volume":"110","author":"Khan","year":"2022","journal-title":"Neuron"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5932","DOI":"10.1016\/j.cell.2021.10.027","article-title":"Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb","volume":"184","author":"Khan","year":"2021","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"002009","DOI":"10.1099\/jgv.0.002009","article-title":"SARS-CoV-2 infects neurons, astrocytes, choroid plexus epithelial cells and pericytes of the human central nervous system in vitro","volume":"105","author":"Haverty","year":"2024","journal-title":"J. Gen. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"sxaf010","DOI":"10.1093\/stmcls\/sxaf010","article-title":"SARS-CoV-2 infection triggers inflammatory conditions and astrogliosis-related gene expression in long-term human cortical organoids","volume":"43","author":"Colinet","year":"2025","journal-title":"Stem Cells"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.stem.2020.12.018","article-title":"ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response","volume":"28","author":"Wang","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1038\/s41380-022-01831-0","article-title":"SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein","volume":"28","author":"Albornoz","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e01091-22","DOI":"10.1128\/spectrum.01091-22","article-title":"SARS-CoV-2 Infection of Microglia Elicits Proinflammatory Activation and Apoptotic Cell Death","volume":"10","author":"Jeong","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s12974-021-02210-2","article-title":"Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: Implications for HIV-1 infection","volume":"18","author":"Torices","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12987-024-00533-9","article-title":"SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway","volume":"21","author":"Yamada","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s11481-024-10127-9","article-title":"Differential Cytokine Responses of APOE3 and APOE4 Blood\u2013brain Barrier Cell Types to SARS-CoV-2 Spike Proteins","volume":"19","author":"Chaves","year":"2024","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Potokar, M., Zorec, R., and Jorga\u010devski, J. (2023). Astrocytes Are a Key Target for Neurotropic Viral Infection. Cells, 12.","DOI":"10.3390\/cells12182307"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41593-024-01576-9","article-title":"Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment","volume":"27","author":"Greene","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1007\/s10495-022-01754-9","article-title":"COVID-19 causes neuronal degeneration and reduces neurogenesis in human hippocampus","volume":"27","author":"Bayat","year":"2022","journal-title":"Apoptosis Int. J. Program. Cell Death"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"St\u0119pie\u0144, T., Tarka, S., Chmura, N., Grzegorczyk, M., Acewicz, A., Felczak, P., and Wierzba-Bobrowicz, T. (2023). Influence of SARS-CoV-2 on Adult Human Neurogenesis. Cells, 12.","DOI":"10.3390\/cells12020244"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101937","DOI":"10.1016\/j.pneurobio.2020.101937","article-title":"Astrocyte-derived Wnt growth factors are required for endothelial blood-brain barrier maintenance","volume":"199","author":"Fidan","year":"2021","journal-title":"Prog. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"895429","DOI":"10.3389\/fnmol.2022.895429","article-title":"Endothelial \u03b2-Catenin Deficiency Causes Blood-Brain Barrier Breakdown via Enhancing the Paracellular and Transcellular Permeability","volume":"15","author":"Hussain","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12974-025-03395-6","article-title":"Inhibition of neutrophil extracellular traps alleviates blood-brain barrier disruption and cognitive dysfunction via Wnt3\/\u03b2-catenin\/TCF4 signaling in sepsis-associated encephalopathy","volume":"22","author":"Yue","year":"2025","journal-title":"J. Neuroinflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1038\/s41598-025-85784-8","article-title":"Activation of Wnt\/\u03b2-catenin in neural progenitor cells regulates blood-brain barrier development and promotes neuroinflammation","volume":"15","author":"Sebo","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s12974-024-03261-x","article-title":"Compromised endothelial Wnt\/\u03b2-catenin signaling mediates the blood-brain barrier disruption and leads to neuroinflammation in endotoxemia","volume":"21","author":"Huang","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1073\/pnas.0805165106","article-title":"Wnt\/\u03b2-catenin signaling is required for CNS, but not non-CNS, angiogenesis","volume":"106","author":"Daneman","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eabm4459","DOI":"10.1126\/science.abm4459","article-title":"Engineered Wnt ligands enable blood-brain barrier repair in neurological disorders","volume":"375","author":"Martin","year":"2022","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e43818","DOI":"10.7554\/eLife.43818","article-title":"Low wnt\/\u03b2-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice","volume":"8","author":"Benz","year":"2019","journal-title":"eLife"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nm.4309","article-title":"Gpr124 is essential for blood-brain barrier integrity in central nervous system disease","volume":"23","author":"Chang","year":"2017","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.neuron.2017.07.031","article-title":"Reck and Gpr124 Are Essential Receptor Cofactors for Wnt7a\/Wnt7b-Specific Signaling in Mammalian CNS Angiogenesis and Blood-Brain Barrier Regulation","volume":"95","author":"Cho","year":"2017","journal-title":"Neuron"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Choi, E.Y., Park, H.H., Kim, H., Kim, H.N., Kim, I., Jeon, S., Kim, W., Bae, J.-S., and Lee, W. (2020). Wnt5a and Wnt11 as acute respiratory distress syndrome biomarkers for SARS-CoV-2 patients. Eur. Respir. J.","DOI":"10.1183\/13993003.01531-2020"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s44298-024-00018-4","article-title":"The Wnt\/\u03b2-catenin pathway is important for replication of SARS-CoV-2 and other pathogenic RNA viruses","volume":"2","author":"Xu","year":"2024","journal-title":"npj Viruses"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1093\/brain\/awae031","article-title":"Engineered Wnt7a ligands rescue blood\u2013brain barrier and cognitive deficits in a COVID-19 mouse model","volume":"147","author":"Trevino","year":"2024","journal-title":"Brain"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mayer, M.G., and Fischer, T. (2025). Shared Mechanisms of Blood-Brain Barrier Dysfunction and Neuroinflammation in Coronavirus Disease 2019 and Alzheimer Disease. Am. J. Pathol.","DOI":"10.1016\/j.ajpath.2025.03.011"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16970","DOI":"10.1073\/pnas.0808616105","article-title":"Wnt-mediated self-renewal of neural stem\/progenitor cells","volume":"105","author":"Kalani","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/nature04108","article-title":"Wnt signalling regulates adult hippocampal neurogenesis","volume":"437","author":"Lie","year":"2005","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4334","DOI":"10.1093\/brain\/awac019","article-title":"Intrinsic blood-brain barrier dysfunction contributes to multiple sclerosis pathogenesis","volume":"145","author":"Nishihara","year":"2022","journal-title":"Brain"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e70992","DOI":"10.7554\/eLife.70992","article-title":"Wnt signaling mediates acquisition of blood-brain barrier properties in na\u00efve endothelium derived from human pluripotent stem cells","volume":"10","author":"Gastfriend","year":"2021","journal-title":"eLife"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19718","DOI":"10.1038\/s41598-019-56075-w","article-title":"Modulation of Wnt\/\u03b2-catenin signaling promotes blood-brain barrier phenotype in cultured brain endothelial cells","volume":"9","author":"Laksitorini","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s11481-012-9411-y","article-title":"Interplay between Wnt\/\u03b2-catenin signaling and HIV: Virologic and biologic consequences in the CNS","volume":"7","year":"2012","journal-title":"J. Neuroimmune Pharmacol. Off. J. Soc. NeuroImmune Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s11481-012-9412-x","article-title":"Wnt\/beta-catenin and its diverse physiological cell signaling pathways in neurodegenerative and neuropsychiatric disorders","volume":"7","year":"2012","journal-title":"J. Neuroimmune Pharmacol. Off. J. Soc. NeuroImmune Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2174\/1570162X12666140526122249","article-title":"\u03b2-Catenin\/TCF-4 signaling regulates susceptibility of macrophages and resistance of monocytes to HIV-1 productive infection","volume":"12","author":"Aljawai","year":"2014","journal-title":"Curr. HIV Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s11481-011-9266-7","article-title":"Role of \u03b2-catenin\/TCF-4 signaling in HIV replication and pathogenesis: Insights to informing novel anti-HIV molecular therapeutics","volume":"6","author":"Henderson","year":"2011","journal-title":"J. Neuroimmune Pharmacol. Off. J. Soc. NeuroImmune Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1128\/JVI.06266-11","article-title":"Role of \u03b2-catenin and TCF\/LEF family members in transcriptional activity of HIV in astrocytes","volume":"86","author":"Narasipura","year":"2012","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e0070521","DOI":"10.1128\/JVI.00705-21","article-title":"\u03b2-Catenin Restricts Zika Virus Internalization by Downregulating Axl","volume":"95","author":"Jimenez","year":"2021","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E1168","DOI":"10.1073\/pnas.1609905114","article-title":"Endothelial Wnt\/\u03b2-catenin signaling reduces immune cell infiltration in multiple sclerosis","volume":"114","author":"Lengfeld","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3389\/fimmu.2018.00217","article-title":"The Role of Astrocytes in Multiple Sclerosis","volume":"9","author":"Ponath","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.4103\/1673-5374.238606","article-title":"Loss of canonical Wnt signaling is involved in the pathogenesis of Alzheimer\u2019s disease","volume":"13","author":"Inestrosa","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13041-019-0525-5","article-title":"Restoring Wnt\/\u03b2-catenin signaling is a promising therapeutic strategy for Alzheimer\u2019s disease","volume":"12","author":"Jia","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1007\/s11481-012-9417-5","article-title":"Wnt signaling: Role in Alzheimer disease and schizophrenia","volume":"7","author":"Inestrosa","year":"2012","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1042\/BST20120122","article-title":"The importance of Wnt signaling for neurodegeneration in Parkinson\u2019s Disease","volume":"40","author":"Berwick","year":"2012","journal-title":"Biochem. Soc. Trans."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/jmcb\/mjt053","article-title":"Targeting Wnt signaling at the neuroimmune interface for dopaminergic neuroprotection\/repair in Parkinson\u2019s disease","volume":"6","author":"Tirolo","year":"2014","journal-title":"J. Mol. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.celrep.2017.04.021","article-title":"Huntington\u2019s disease iPSC-derived brain microvascular endothelial cells reveal WNT-mediated angiogenic and blood-brain barrier deficits","volume":"19","author":"Lim","year":"2017","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101963","DOI":"10.1016\/j.pneurobio.2020.101963","article-title":"Activation of endothelial Wnt\/\u03b2-catenin signaling by protective astrocytes repairs BBB damage in ischemic stroke","volume":"199","author":"Song","year":"2021","journal-title":"Prog. Neurobiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s12035-024-04303-4","article-title":"Astrocytes-Secreted WNT5B Disrupts the Blood-Brain Barrier Via ROR1\/JNK\/c-JUN Cascade During Meningitic Escherichia Coli Infection","volume":"62","author":"Qu","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_63","first-page":"3570","article-title":"Reduction in paracrine Wnt3 factors during aging causes impaired adult neurogenesis","volume":"25","author":"Okamoto","year":"2011","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1128\/JVI.80.1.541-544.2006","article-title":"Gamma interferon primes productive human immunodeficiency virus infection in astrocytes","volume":"80","year":"2006","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6771","DOI":"10.4049\/jimmunol.1100099","article-title":"IFN-\u03b3 mediates enhancement of HIV replication in astrocytes by inducing an antagonist of the \u03b2-catenin pathway (DKK1) in a STAT 3-dependent manner","volume":"186","author":"Li","year":"2011","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"16306","DOI":"10.1523\/JNEUROSCI.3145-12.2012","article-title":"Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription through its intact core and cysteine-rich domains inhibits Wnt\/\u03b2-catenin signaling in astrocytes: Relevance to HIV neuropathogenesis","volume":"32","author":"Henderson","year":"2012","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e1008381","DOI":"10.1371\/journal.ppat.1008381","article-title":"HIV infects astrocytes in vivo and egresses from the brain to the periphery","volume":"16","author":"Lutgen","year":"2020","journal-title":"PLoS Pathog."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12964-020-00565-2","article-title":"\u03b2-Catenin and TCFs\/LEF signaling discordantly regulate IL-6 expression in astrocytes","volume":"18","author":"Robinson","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s12974-016-0691-7","article-title":"\u03b2-Catenin signaling positively regulates glutamate uptake and metabolism in astrocytes","volume":"13","author":"Lutgen","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5864","DOI":"10.1128\/JVI.02234-06","article-title":"Human immunodeficiency virus-restricted replication in astrocytes and the ability of gamma interferon to modulate this restriction are regulated by a downstream effector of the Wnt signaling pathway","volume":"81","author":"Kumar","year":"2007","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9495","DOI":"10.1128\/JVI.00486-12","article-title":"Identification of novel T cell factor 4 (TCF-4) binding sites on the HIV long terminal repeat which associate with TCF-4, \u03b2-catenin, and SMAR1 to repress HIV transcription","volume":"86","author":"Henderson","year":"2012","journal-title":"J. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.7150\/ijbs.4679","article-title":"Interleukin-6, a major cytokine in the central nervous system","volume":"8","author":"Erta","year":"2012","journal-title":"Int. J. Biol. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.it.2014.12.008","article-title":"Versatile functions for IL-6 in metabolism and cancer","volume":"36","author":"Mauer","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.bbamcr.2016.03.018","article-title":"The role of interleukin-6 signaling in nervous tissue","volume":"1863","author":"Rothaug","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"155252","DOI":"10.1016\/j.cyto.2020.155252","article-title":"Negative regulation of IL-8 in human astrocytes depends on \u03b2-catenin while positive regulation is mediated by TCFs\/LEF\/ATF2 interaction","volume":"136","author":"Robinson","year":"2020","journal-title":"Cytokine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1215\/S1152851704001061","article-title":"The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis","volume":"7","author":"Brat","year":"2005","journal-title":"Neuro-Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1089\/107999099313866","article-title":"Regulation of interleukin-8 gene expression","volume":"19","author":"Roebuck","year":"1999","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1111\/acel.12593","article-title":"HIV and drug abuse mediate astrocyte senescence in a beta-catenin-dependent manner leading to neuronal toxicity","volume":"16","author":"Yu","year":"2017","journal-title":"Aging Cell"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Hou, J., Kim, S., Sung, C., and Choi, C. (2017). Ginsenoside Rg3 prevents oxidative stress-induced astrocytic senescence and ameliorates senescence paracrine effects on glioblastoma. Molecules, 22.","DOI":"10.3390\/molecules22091516"},{"key":"ref_80","first-page":"58","article-title":"Wnt\/\u03b2-Catenin Signaling in Neural Stem Cell Homeostasis and Neurological Diseases","volume":"27","author":"Gao","year":"2020","journal-title":"Neurosci. Rev. J. Bringing Neurobiol. Neurol. Psychiatry"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Gonzalez, H., Narasipura, S.D., Shull, T., Shetty, A., Teppen, T.L., Naqib, A., and Al-Harthi, L. (2023). An Efficient and Cost-Effective Approach to Generate Functional Human Inducible Pluripotent Stem Cell-Derived Astrocytes. Cells, 12.","DOI":"10.3390\/cells12192357"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Chang, C.-Y., Liang, M.-Z., Wu, C.-C., Huang, P.-Y., Chen, H.-I., Yet, S.-F., Tsai, J.-W., Kao, C.-F., and Chen, L. (2020). WNT3A Promotes Neuronal Regeneration upon Traumatic Brain Injury. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041463"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1177\/0271678X17702669","article-title":"Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice","volume":"38","author":"Wei","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.celrep.2017.06.009","article-title":"Exosomes Mediate Mobilization of Autocrine Wnt10b to Promote Axonal Regeneration in the Injured CNS","volume":"20","author":"Tassew","year":"2017","journal-title":"Cell Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.3389\/fimmu.2019.02872","article-title":"Wnt Signaling and Its Significance Within the Tumor Microenvironment: Novel Therapeutic Insights","volume":"10","author":"Patel","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/glia.22763","article-title":"Dynamic interaction between astrocytes and infiltrating PBMCs in context of neuroAIDS","volume":"63","author":"Richards","year":"2015","journal-title":"Glia"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e2101181","DOI":"10.1002\/advs.202101181","article-title":"Reduced Oligodendrocyte Precursor Cell Impairs Astrocytic Development in Early Life Stress","volume":"8","author":"Wang","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41590-023-01724-6","article-title":"Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2","volume":"25","author":"Yin","year":"2024","journal-title":"Nat. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"104552","DOI":"10.1016\/j.ebiom.2023.104552","article-title":"Cellular and molecular biomarkers of long COVID: A scoping review","volume":"91","author":"Yang","year":"2023","journal-title":"eBioMedicine"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41590-021-01113-x","article-title":"Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection","volume":"23","author":"Phetsouphanh","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0165-5728(02)00097-8","article-title":"Multiple sclerosis: A study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system","volume":"127","author":"Sorensen","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6873","DOI":"10.1073\/pnas.96.12.6873","article-title":"CCR5+ and CXCR3+ T cells are increased in multiple sclerosis and their ligands MIP-1\u03b1 and IP-10 are expressed in demyelinating brain lesions","volume":"96","author":"Balashov","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S0165-5728(01)00261-2","article-title":"Serum and CSF levels of MCP-1 and IP-10 in multiple sclerosis patients with acute and stable disease and undergoing immunomodulatory therapies","volume":"115","author":"Franciotta","year":"2001","journal-title":"J. Neuroimmunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.neurobiolaging.2017.11.009","article-title":"Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance","volume":"63","author":"Bradburn","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"9214","DOI":"10.1128\/JVI.74.19.9214-9221.2000","article-title":"Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes","volume":"74","author":"Kutsch","year":"2000","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S0165-5728(98)00223-9","article-title":"Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1-infected individuals as interferon-\u03b3 inducible protein 10","volume":"93","author":"Kolb","year":"1999","journal-title":"J. Neuroimmunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1097\/00002030-199809000-00009","article-title":"Chemokines and receptors in HIV encephalitis","volume":"12","author":"Sanders","year":"1998","journal-title":"Aids"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Oh, S.J., Kumari, P., Auroni, T.T., Stone, S., Pathak, H., Elsharkawy, A., Natekar, J.P., Shin, O.S., and Kumar, M. (2024). Upregulation of Neuroinflammation-Associated Genes in the Brain of SARS-CoV-2-Infected Mice. Pathogens, 13.","DOI":"10.3390\/pathogens13070528"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kumari, P., Rothan, H.A., Natekar, J.P., Stone, S., Pathak, H., Strate, P.G., Arora, K., Brinton, M.A., and Kumar, M. (2021). Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice. Viruses, 13.","DOI":"10.1101\/2020.12.14.422714"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Carossino, M., Kenney, D., O\u2019Connell, A.K., Montanaro, P., Tseng, A.E., Gertje, H.P., Grosz, K.A., Ericsson, M., Huber, B.R., and Kurnick, S.A. (2022). Fatal Neurodissemination and SARS-CoV-2 Tropism in K18-hACE2 Mice Is Only Partially Dependent on hACE2 Expression. Viruses, 14.","DOI":"10.3390\/v14030535"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Seehusen, F., Clark, J.J., Sharma, P., Bentley, E.G., Kirby, A., Subramaniam, K., Wunderlin-Giuliani, S., Hughes, G.L., Patterson, E.I., and Michael, B.D. (2022). Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse. Viruses, 14.","DOI":"10.3390\/v14051020"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Rothan, H.A., Kumari, P., Stone, S., Natekar, J.P., Arora, K., Auroni, T.T., and Kumar, M. (2022). SARS-CoV-2 Infects Primary Neurons from Human ACE2 Expressing Mice and Upregulates Genes Involved in the Inflammatory and Necroptotic Pathways. Pathogens, 11.","DOI":"10.3390\/pathogens11020257"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/10\/994\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T04:13:46Z","timestamp":1759551226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/10\/994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":102,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["pathogens14100994"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14100994","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,2]]}}}