{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:06:44Z","timestamp":1788394004345,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA11810040"],"award-info":[{"award-number":["HDTRA11810040"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-23-1-0003"],"award-info":[{"award-number":["HDTRA1-23-1-0003"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["UH3TR002097"],"award-info":[{"award-number":["UH3TR002097"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA11810040"],"award-info":[{"award-number":["HDTRA11810040"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-23-1-0003"],"award-info":[{"award-number":["HDTRA1-23-1-0003"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["UH3TR002097"],"award-info":[{"award-number":["UH3TR002097"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Center for Advancing Translational Sciences of the National Institutes of Health","doi-asserted-by":"publisher","award":["HDTRA11810040"],"award-info":[{"award-number":["HDTRA11810040"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Center for Advancing Translational Sciences of the National Institutes of Health","doi-asserted-by":"publisher","award":["HDTRA1-23-1-0003"],"award-info":[{"award-number":["HDTRA1-23-1-0003"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Center for Advancing Translational Sciences of the National Institutes of Health","doi-asserted-by":"publisher","award":["UH3TR002097"],"award-info":[{"award-number":["UH3TR002097"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The blood brain barrier (BBB) is a multicellular microenvironment that plays an important role in regulating bidirectional transport to and from the central nervous system (CNS). Infections by many acutely infectious viruses such as alphaviruses and flaviviruses are known to impact the integrity of the endothelial lining of the BBB. Infection by Venezuelan Equine Encephalitis Virus (VEEV) through the aerosol route causes significant damage to the integrity of the BBB, which contributes to long-term neurological sequelae. An effective therapeutic intervention strategy should ideally not only control viral load in the host, but also prevent and\/or reverse deleterious events at the BBB. Two dimensional monocultures, including trans-well models that use endothelial cells, do not recapitulate the intricate multicellular environment of the BBB. Complex in vitro organ-on-a-chip models (OOC) provide a great opportunity to introduce human-like experimental models to understand the mechanistic underpinnings of the disease state and evaluate the effectiveness of therapeutic candidates in a highly relevant manner. Here we demonstrate the utility of a neurovascular unit (NVU) in analyzing the dynamics of infection and proinflammatory response following VEEV infection and therapeutic effectiveness of omaveloxolone to preserve BBB integrity and decrease viral and inflammatory load.<\/jats:p>","DOI":"10.3390\/v14122799","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T04:25:26Z","timestamp":1671078326000},"page":"2799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2678-6481","authenticated-orcid":false,"given":"Niloufar A.","family":"Boghdeh","sequence":"first","affiliation":[{"name":"Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6999-7564","authenticated-orcid":false,"given":"Kenneth H.","family":"Risner","sequence":"additional","affiliation":[{"name":"Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA"},{"name":"College of Science, School of Systems Biology, George Mason University, Manassas, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Barrera","sequence":"additional","affiliation":[{"name":"Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA"},{"name":"College of Science, School of Systems Biology, George Mason University, Manassas, VA 20110, USA"},{"name":"College of Science, Department of Biology, George Mason University, Fairfax, VA 22030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton M.","family":"Britt","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37212, USA"},{"name":"Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Schaffer","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37212, USA"},{"name":"Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-2502","authenticated-orcid":false,"given":"Farhang","family":"Alem","sequence":"additional","affiliation":[{"name":"Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37212, USA"},{"name":"Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Wikswo","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37212, USA"},{"name":"Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235, USA"},{"name":"Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA"},{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarthi","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Biomedical Research Laboratory, Institute of Biohealth Innovation, George Mason University, Manassas, VA 20110, USA"},{"name":"College of Science, Department of Biology, George Mason University, Fairfax, VA 22030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev.ento.49.061802.123422","article-title":"Venezuelan equine encephalitis","volume":"49","author":"Weaver","year":"2004","journal-title":"Annu. Rev. Entomol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.2042-3306.1976.tb03293.x","article-title":"Equine viral encephalitis","volume":"8","author":"Gibbs","year":"1976","journal-title":"Equine Vet. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.vetmic.2013.07.012","article-title":"Pathogenesis of Venezuelan equine encephalitis","volume":"167","author":"Taylor","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.tmaid.2017.02.007","article-title":"Venezuelan equine encephalitis: How likely are we to see the next epidemic","volume":"17","author":"Blohm","year":"2017","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20412","DOI":"10.1101\/cshperspect.a020412","article-title":"The blood-brain barrier","volume":"7","author":"Daneman","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood-brain barrier","volume":"37","author":"Abbott","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial interactions at the blood-brain barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00401-018-1815-1","article-title":"Functional morphology of the blood-brain barrier in health and disease","volume":"135","author":"Liebner","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1084\/jem.20190062","article-title":"The blood-barrier in health and disease: Important unanswered questions","volume":"217","author":"Profaci","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1007\/s10753-021-01501-3","article-title":"Sepsis-Associated Encephalopathy and Blood-Brain Barrier Dysfunction","volume":"44","author":"Gao","year":"2021","journal-title":"Inflammation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1038\/s41423-021-00757-x","article-title":"The blood-brain barrier in systemic infection and inflammation","volume":"18","author":"Galea","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10682","DOI":"10.1128\/JVI.05032-11","article-title":"The role of the blood-brain barrier during Venezuelan equine encephalitis virus infection","volume":"85","author":"Brooke","year":"2011","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jneuroim.2017.04.008","article-title":"Virus entry and replication in the brain precedes blood-brain barrier disruption during intranasal alphavirus infection","volume":"308","author":"Cain","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1080\/21505594.2020.1870834","article-title":"Toll-like receptor 4 mediates blood-brain barrier permeability and disease in C3H mice during Venezuelan equine encephalitis virus infection","volume":"12","author":"Hollidge","year":"2021","journal-title":"Virulence"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.3390\/v11111052","article-title":"Characterization of Brain Inflammation, Apoptosis, Hypoxia, Blood-Brain Barrier Integrity and Metabolism in Venezuelan Equine Encephalitis Virus (VEEV TC-83) Exposed Mice by in Vivo Positron Emission Tomography Imaging","volume":"11","author":"Bocan","year":"2019","journal-title":"Viruses"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1177\/0300985810372508","article-title":"Pathology of animal models of alphavirus encephalitis","volume":"47","author":"Steele","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.tim.2016.06.002","article-title":"Neuroteratogenic Viruses and Lessons for Zika Virus Models","volume":"24","author":"Kim","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"380","DOI":"10.30802\/AALAS-CM-18-000027","article-title":"Comparison of Aerosol- and Percutaneous-acquired Venezuelan Equine Encephalitis in Humans and Nonhuman Primates for Suitability in Predicting Clinical Efficacy under the Animal Rule","volume":"68","author":"Rusnak","year":"2018","journal-title":"Comp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1186\/scrt379","article-title":"Neurovascular unit on a chip: Implications for translational applications","volume":"4","author":"Alcendor","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"54124","DOI":"10.1063\/1.4934713","article-title":"Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor","volume":"9","author":"Brown","year":"2015","journal-title":"Biomicrofluidics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/s12974-016-0760-y","article-title":"Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the huma neurovascular unit","volume":"13","author":"Brown","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12987-020-00200-9","article-title":"Advances in blood-brain barrier modeling in organ on a chips highlight critical differences in opioid transport due to cortisol exposure","volume":"17","author":"Brown","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4564471","DOI":"10.1155\/2022\/4564471","article-title":"The Novel Nrf2 Activator Omaveloxolone Regulates Microglia Phenotype and Ameliorates Secondary Brain Injury after Intracerebral Hemorrhage in Mice","volume":"2022","author":"Hu","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1080\/17435390.2021.1919330","article-title":"Stabilization of Nrf2 leading to HO-1 activation protects against zinc oxide nanoparticles-induced endothelial cell death","volume":"15","author":"Zhang","year":"2021","journal-title":"Nanotoxicology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4239","DOI":"10.2147\/OTT.S136992","article-title":"Safety, pharmacokinetics, and pharmacodynamics of oral omaveloxolone (RTA 408), a synthetic triterpenoid, in a first-in-human trial of patients with advanced solid tumors","volume":"10","author":"Creelan","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bakovic, A., Bhalla, N., Alem, F., Campbell, C., Zhou, W., and Narayanan, A. (2021). Inhibitors of Venezuelan Equine Encephalitis Virus Identified Based on Host Interaction Partners of Viral Non-Structural Protein 3. Viruses, 13.","DOI":"10.3390\/v13081533"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Risner, K., Ahmed, A., Bakovic, A., Kortchak, S., Bhalla, N., and Narayanan, A. (2019). Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection. Viruses, 11.","DOI":"10.3390\/v11121151"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bakovic, A., Bhalla, N., Kortchak, S., Sun, C., Zhou, W., Ahmed, A., Risner, K., Klimstra, W.B., and Narayanan, A. (2020). Venezuelan Equine Encephalitis Virus nsP3 Phosphorylation Can Be Mediated by IKK\u03b2 Kinase Activity and Abrogation of Phosphorylation Inhibits Negative-Strand Synthesis. Viruses, 12.","DOI":"10.3390\/v12091021"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Amaya, M., Keck, F., Lindquist, M., Voss, K., Scavone, L., Kehn-Hall, K., Roberts, B., Bailey, C., Schmaljohn, C., and Narayanan, A. (2015). The ubiquitin proteasome system plays a role in venezuelan equine encephalitis virus infection. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124792"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.virol.2014.09.005","article-title":"Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells","volume":"468\u2013470","author":"Voss","year":"2014","journal-title":"Virology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12941-020-00360-4","article-title":"Venezuelan equine encephalitis virus: The problem is 185 not over for tropical America","volume":"19","author":"Mattar","year":"2020","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103140","DOI":"10.1016\/j.jevs.2020.103140","article-title":"National Seroprevalence and Risk Factors for Eastern Equine Encephalitis and Venezuelan Equine Encephalitis in Costa Rica","volume":"92","author":"Hutter","year":"2020","journal-title":"J. Equine Vet. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"454","DOI":"10.3201\/eid1403.070816","article-title":"Molecular epidemiology of eastern equine encephalitis virus","volume":"14","author":"Young","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1089\/vbz.2020.2671","article-title":"Eastern Equine Encephalitis Virus: A Scoping Review of the Global Evidence","volume":"21","author":"Corrin","year":"2021","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jme\/tjab077","article-title":"Ecology and Epidemiology of Eastern Equine Encephalitis Virus in the Northeastern United States: An Historical Perspective","volume":"59","author":"Armstrong","year":"2022","journal-title":"J. Med. Entomol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.tips.2020.11.009","article-title":"Organ-on-a-Chip: A New Paradigm for Drug Development","volume":"42","author":"Ma","year":"2021","journal-title":"Trends Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.dmpk.2017.11.003","article-title":"Organ\/body-on-a-chip based on microfluidic technology for drug discovery","volume":"33","author":"Kimura","year":"2017","journal-title":"Drug Metab. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Cong, Y., Han, X., Wang, Y., Chen, Z., Lu, Y., Liu, T., Wu, Z., Jin, Y., Luo, Y., and Zhang, X. (2020). Drug Toxicity Evaluation Based on Organ-on-a-chip technology: A Review. Micromachines, 11.","DOI":"10.3390\/mi11040381"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1080\/07388551.2019.1710458","article-title":"Long-on-a-chip: The future of respiratory disease models and pharmacological studies","volume":"40","author":"Shrestha","year":"2020","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2002928","DOI":"10.1002\/advs.202002928","article-title":"Biomimetic Human Disease Model of SARS-CoV-2-Induced Lung Injury and Immune Responses on Organ Chip System","volume":"8","author":"Zhang","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.stem.2019.05.011","article-title":"Human iPSC-Derived Blood-Brain Barrier Chips Enable Disease Modeling and Personalized Medicine Applications","volume":"24","author":"Vatine","year":"2019","journal-title":"Cell Stem. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.tim.2020.06.005","article-title":"Human Organs-on-Chips for Virology","volume":"28","author":"Tang","year":"2020","journal-title":"Trends Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"583373","DOI":"10.3389\/fimmu.2020.583373","article-title":"The Inflammasome in Times of COVID-19: A Review","volume":"11","author":"Vaccari","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.3389\/fimmu.2020.01446","article-title":"The COVID-19 Cytokine Storm; What We Know So Far","volume":"11","author":"Ragab","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1053\/j.semdp.2007.07.002","article-title":"The pathology of dengue hemorrhagic fever","volume":"24","author":"Leong","year":"2007","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"452","DOI":"10.3389\/fimmu.2019.00452","article-title":"Contribution of Cytokines to Tissue Damage During Human Respiratory Syncytial Virus Infection","volume":"10","author":"Bohmwald","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s12974-019-1596-z","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":"Palus","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bass, A., Liu, Y., and Dakshanamurthy, S. (2021). Single-Cell and Bulk RNASeq Profiling of COVID-19 Patients Reveal Immune and Inflammatory Mechanisms of Infection-Induced Organ Damage. Viruses, 13.","DOI":"10.3390\/v13122418"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0966-842X(01)02200-4","article-title":"Recent insights into poliovirus pathogenesis","volume":"9","author":"Ohka","year":"2001","journal-title":"Trends Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4016","DOI":"10.1038\/sj.emboj.7601831","article-title":"Poliovirus entry into human brain microvascular cells requires receptor-induced activation of SHP-2","volume":"26","author":"Coyne","year":"2007","journal-title":"EMBO J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.3389\/fmicb.2019.01435","article-title":"Dengue Virus Infection of Blood-Brain Barrier Cells: Consequences of Severe Disease","volume":"10","author":"Castellanos","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1007\/s00705-019-04175-3","article-title":"Invasion of a murine in vitro blood-brain barrier co-culture model by dengue virus serotypes 1 to 4","volume":"164","author":"Idris","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.virol.2018.10.021","article-title":"Vascular permeability in the brain is a late pathogenic event during Rift Valley fever virus encephalitis in rats","volume":"526","author":"Walters","year":"2019","journal-title":"Virology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1099\/0022-1317-72-4-859","article-title":"Breakdown of the blood-brain barrier during dengue virus infection of mice","volume":"72","author":"Chaturvedi","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1099\/jgv.0.001522","article-title":"Development of Rift valley fever encephalitis in rats is mediated by early infection of olfactory epithelium and neuroinvasion across the cribriform plate","volume":"102","author":"Boyles","year":"2021","journal-title":"J. Gen. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"27670","DOI":"10.1038\/srep27670","article-title":"Microglia retard dengue virus-induced acute viral encephalitis","volume":"6","author":"Tsai","year":"2016","journal-title":"Sci. Rep."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/12\/2799\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:50Z","timestamp":1760146910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/12\/2799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,15]]},"references-count":56,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["v14122799"],"URL":"https:\/\/doi.org\/10.3390\/v14122799","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,15]]}}}