{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:27:40Z","timestamp":1788319660061,"version":"build-2803163510"},"reference-count":63,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"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, USA","doi-asserted-by":"publisher","award":["HDTRA117-CBMB-05-2-0008"],"award-info":[{"award-number":["HDTRA117-CBMB-05-2-0008"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Venezuelan equine encephalitis virus (VEEV) is a disease typically confined to South and Central America, whereby human disease is characterised by a transient systemic infection and occasionally severe encephalitis, which is associated with lethality. Using an established mouse model of VEEV infection, the encephalitic aspects of the disease were analysed to identify biomarkers associated with inflammation. Sequential sampling of lethally challenged mice (infected subcutaneously) confirmed a rapid onset systemic infection with subsequent spread to the brain within 24 h of the challenge. Changes in inflammatory biomarkers (TNF-\u03b1, CCL-2, and CCL-5) and CD45+ cell counts were found to correlate strongly to pathology (R&gt;0.9) and present previously unproven biomarkers for disease severity in the model, more so than viral titre. The greatest level of pathology was observed within the olfactory bulb and midbrain\/thalamus. The virus was distributed throughout the brain\/encephalon, often in areas not associated with pathology. The principal component analysis identified five principal factors across two independent experiments, with the first two describing almost half of the data: (1) confirmation of a systemic Th1-biased inflammatory response to VEEV infection, and (2) a clear correlation between specific inflammation of the brain and clinical signs of disease. Targeting strongly associated biomarkers of deleterious inflammation may ameliorate or even eliminate the encephalitic syndrome of this disease.<\/jats:p>","DOI":"10.3390\/v15061307","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T01:40:56Z","timestamp":1685583656000},"page":"1307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Tumour Necrosis Factor-\u03b1, Chemokines, and Leukocyte Infiltrate Are Biomarkers for Pathology in the Brains of Venezuelan Equine Encephalitis (VEEV)-Infected Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Amanda L.","family":"Phelps","sequence":"first","affiliation":[{"name":"Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Salguero","sequence":"additional","affiliation":[{"name":"UK Health Security Agency, Salisbury SP4 0JG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8698-8280","authenticated-orcid":false,"given":"Laura","family":"Hunter","sequence":"additional","affiliation":[{"name":"UK Health Security Agency, Salisbury SP4 0JG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander L.","family":"Stoll","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic C.","family":"Jenner","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyn M.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0322-5972","authenticated-orcid":false,"given":"E. Diane","family":"Williamson","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Stephen","family":"Lever","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0142-9162","authenticated-orcid":false,"given":"Thomas R.","family":"Laws","sequence":"additional","affiliation":[{"name":"Defence Science and Technology Laboratory, Salisbury SP4 0JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"ref_1","first-page":"721","article-title":"Venezuelan equine encephalitis\u2014Colombia, 1995","volume":"44","author":"Daza","year":"1995","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1126\/science.158.3806.1283","article-title":"Arbovirus infections of laboratory workers. Extent of problem emphasizes the need for more effective measures to reduce hazards","volume":"158","author":"Hanson","year":"1967","journal-title":"Science"},{"key":"ref_3","unstructured":"Bozue, J., Cote, C.K., and Glass, P.J. (2018). Medical Aspects of Biological Warfare, Borden Institute."},{"key":"ref_4","unstructured":"(2023, April 20). Special Immunizations Program. Available online: https:\/\/www.usammda.army.mil\/index.cfm\/fhp\/immunizations_program."},{"key":"ref_5","unstructured":"Bozue, J., Cote, C.K., and Glass, P.J. (2018). Medical Aspects of Biological Warfare, Borden Institute."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Stromberg, Z.R., Fischer, W., Bradfute, S.B., Kubicek-Sutherland, J.Z., and Hraber, P. (2020). Vaccine Advances against Venezuelan, Eastern, and Western Equine Encephalitis Viruses. Vaccines, 8.","DOI":"10.3390\/vaccines8020273"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Burke, C.W., Erwin-Cohen, R.A., Goodson, A.I., Wilhelmsen, C., Edmundson, J.A., White, C.E., and Glass, P.J. (2022). Efficacy of Western, Eastern, and Venezuelan Equine Encephalitis (WEVEE) Virus-Replicon Particle (VRP) Vaccine against WEEV in a Non-Human Primate Animal Model. Viruses, 14.","DOI":"10.3390\/v14071502"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3378","DOI":"10.1016\/j.vaccine.2020.02.007","article-title":"Venezuelan equine encephalitis vaccine with rearranged genome resists reversion and protects non-human primates from viremia after aerosol challenge","volume":"38","author":"Tretyakova","year":"2020","journal-title":"Vaccine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12077","DOI":"10.1128\/JVI.01406-14","article-title":"Combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses","volume":"88","author":"Reed","year":"2014","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/S1473-3099(22)00052-4","article-title":"Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: A phase 1, open-label, dose-escalation, randomised clinical trial","volume":"22","author":"Coates","year":"2022","journal-title":"Lancet. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1016\/j.vaccine.2016.04.077","article-title":"A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation","volume":"34","author":"Hannaman","year":"2016","journal-title":"Vaccine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/S0264-410X(01)00505-9","article-title":"Monoclonal antibody protects mice against infection and disease when given either before or up to 24 h after airborne challenge with virulent Venezuelan equine encephalitis virus","volume":"20","author":"Phillpotts","year":"2002","journal-title":"Vaccine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1089\/10799900360520441","article-title":"Antibody and interleukin-12 treatment in murine models of encephalitogenic flavivirus (St. Louis encephalitis, tick-borne encephalitis) and alphavirus (Venezuelan equine encephalitis) infection","volume":"23","author":"Phillpotts","year":"2003","journal-title":"J. Interferon Cytokine Res. Off. J. Int. Soc. Interferon Cytokine Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1099\/vir.0.81925-0","article-title":"A humanized murine monoclonal antibody protects mice either before or after challenge with virulent Venezuelan equine encephalomyelitis virus","volume":"87","author":"Hunt","year":"2006","journal-title":"J. Gen. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.virusres.2006.02.003","article-title":"Venezuelan equine encephalitis virus complex-specific monoclonal antibody provides broad protection, in murine models, against airborne challenge with viruses from serogroups I, II and III","volume":"120","author":"Phillpotts","year":"2006","journal-title":"Virus Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/1743-422X-6-206","article-title":"Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains","volume":"6","author":"Goodchild","year":"2009","journal-title":"Virol. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5558","DOI":"10.1016\/j.vaccine.2010.06.038","article-title":"A recombinant humanized monoclonal antibody completely protects mice against lethal challenge with Venezuelan equine encephalitis virus","volume":"28","author":"Hu","year":"2010","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12683","DOI":"10.1128\/JVI.01345-10","article-title":"Antibody to the E3 glycoprotein protects mice against lethal venezuelan equine encephalitis virus infection","volume":"84","author":"Parker","year":"2010","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2011.01.010","article-title":"A humanised murine monoclonal antibody with broad serogroup specificity protects mice from challenge with Venezuelan equine encephalitis virus","volume":"90","author":"Goodchild","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.virol.2011.03.016","article-title":"Treatment of mice with human monoclonal antibody 24h after lethal aerosol challenge with virulent Venezuelan equine encephalitis virus prevents disease but not infection","volume":"414","author":"Hunt","year":"2011","journal-title":"Virology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.virol.2012.01.038","article-title":"A humanised murine monoclonal antibody protects mice from Venezuelan equine encephalitis virus, Everglades virus and Mucambo virus when administered up to 48 h after airborne challenge","volume":"426","author":"Goodchild","year":"2012","journal-title":"Virology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Burke, C.W., Froude, J.W., Rossi, F., White, C.E., Moyer, C.L., Ennis, J., Pitt, M.L., Streatfield, S., Jones, R.M., and Musiychuk, K. (2019). Therapeutic monoclonal antibody treatment protects nonhuman primates from severe Venezuelan equine encephalitis virus disease after aerosol exposure. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1008157"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e20212532","DOI":"10.1084\/jem.20212532","article-title":"Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge","volume":"219","author":"Kafai","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5006","DOI":"10.1128\/JVI.74.11.5006-5015.2000","article-title":"Pegylated alpha interferon is an effective treatment for virulent venezuelan equine encephalitis virus and has profound effects on the host immune response to infection","volume":"74","author":"Lukaszewski","year":"2000","journal-title":"J. Virol."},{"key":"ref_25","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_26","unstructured":"(2023, April 20). RECOVERY Randomised Evaluation of COVID-19 Therapy. Available online: https:\/\/www.recoverytrial.net\/."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1177\/2040206616660851","article-title":"Melatonin decreases brain apoptosis, oxidative stress, and CD200 expression and increased survival rate in mice infected by Venezuelan equine encephalitis virus","volume":"24","author":"Montiel","year":"2016","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s12974-016-0683-7","article-title":"Type-1 angiotensin receptor signaling in central nervous system myeloid cells is pathogenic during fatal alphavirus encephalitis in mice","volume":"13","author":"Blakely","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1097\/01.jnen.0000263867.46070.e2","article-title":"Neuroprotective interventions targeting detrimental host immune responses protect mice from fatal alphavirus encephalitis","volume":"66","author":"Irani","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_30","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":"Schafer","year":"2011","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sharma, A., Bhattacharya, B., Puri, R.K., and Maheshwari, R.K. (2008). Venezuelan equine encephalitis virus infection causes modulation of inflammatory and immune response genes in mouse brain. BMC Genom., 9.","DOI":"10.1186\/1471-2164-9-289"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/1743-422X-8-197","article-title":"Role of adhesion molecules and inflammation in Venezuelan equine encephalitis virus infected mouse brain","volume":"8","author":"Sharma","year":"2011","journal-title":"Virol. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/S0165-5728(00)00290-3","article-title":"Inflammation is a component of neurodegeneration in response to Venezuelan equine encephalitis virus infection in mice","volume":"109","author":"Schoneboom","year":"2000","journal-title":"J. Neuroimmunol."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","unstructured":"Bocan, T.M., Stafford, R.G., Brown, J.L., Akuoku Frimpong, J., Basuli, F., Hollidge, B.S., Zhang, X., Raju, N., Swenson, R.E., and Smith, D.R. (2019). 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. Viruses, 11.","DOI":"10.3390\/v11111052"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1006\/viro.2001.0878","article-title":"Immunopathogenesis and immune modulation of Venezuelan equine encephalitis virus-induced disease in the mouse","volume":"284","author":"Charles","year":"2001","journal-title":"Virology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1177\/0300985810372508","article-title":"REVIEW PAPER: Pathology of animal models of alphavirus encephalitis","volume":"47","author":"Steele","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1600-065X.2006.00441.x","article-title":"CNS immune privilege: Hiding in plain sight","volume":"213","author":"Carson","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1016\/j.vaccine.2004.06.056","article-title":"Intranasal immunisation with defective adenovirus serotype 5 expressing the Venezuelan equine encephalitis virus E2 glycoprotein protects against airborne challenge with virulent virus","volume":"23","author":"Phillpotts","year":"2005","journal-title":"Vaccine"},{"key":"ref_40","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_41","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_42","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.4049\/jimmunol.1202246","article-title":"IL-4 in the Brain: A Cytokine to Remember","volume":"189","author":"Gadani","year":"2012","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1056\/NEJMra0707449","article-title":"Interleukin-17 and type 17 helper T cells","volume":"361","author":"Miossec","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e01476-14","DOI":"10.1128\/mBio.01476-14","article-title":"Viral pathogen-associated molecular patterns regulate blood-brain barrier integrity via competing innate cytokine signals","volume":"5","author":"Daniels","year":"2014","journal-title":"mBio"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1021\/acschemneuro.6b00043","article-title":"The Olfactory Bulb: An Immunosensory Effector Organ during Neurotropic Viral Infections","volume":"7","author":"Durrant","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1080\/14787210.2018.1496330","article-title":"The treatment of melioidosis: Is there a role for repurposed drugs? A proposal and review","volume":"17","author":"Laws","year":"2019","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"RECOVERY Collaborative Group (2020). Dexamethasone in Hospitalized Patients with COVID-19. N. Engl. J. Med., 384, 693\u2013704.","DOI":"10.1056\/NEJMoa2021436"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1124\/mol.107.038794","article-title":"Separating transrepression and transactivation: A distressing divorce for the glucocorticoid receptor?","volume":"72","author":"Newton","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/S0140-6736(21)00676-0","article-title":"Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial","volume":"397","author":"Consortia","year":"2021","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1136\/conmed-2018-000005","article-title":"Interleukin 6: The biology behind the therapy","volume":"2","author":"Jones","year":"2018","journal-title":"Consid. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"45789","DOI":"10.18632\/oncotarget.9953","article-title":"Impaired lymphatic function accelerates cancer growth","volume":"7","author":"Steinskog","year":"2016","journal-title":"Oncotarget"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1093\/infdis\/jir266","article-title":"The combination of a tumor necrosis factor inhibitor and antibiotic alleviates staphylococcal arthritis and sepsis in mice","volume":"204","author":"Fei","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4161\/mabs.2.1.10328","article-title":"Canakinumab","volume":"2","author":"Dhimolea","year":"2010","journal-title":"MAbs"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0955-2235(90)90018-F","article-title":"Interleukin-1 receptor antagonist: Discovery, structure and properties","volume":"2","author":"Arend","year":"1990","journal-title":"Prog. Growth Factor Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ceballos-Olvera, I., Sahoo, M., Miller, M.A., Del Barrio, L., and Re, F. (2011). Inflammasome-dependent pyroptosis and IL-18 protect against Burkholderia pseudomallei lung infection while IL-1beta is deleterious. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002452"},{"key":"ref_56","first-page":"655","article-title":"Selective COX-2 Inhibitors: A Review of Their Structure-Activity Relationships","volume":"10","author":"Zarghi","year":"2011","journal-title":"Iran. J. Pharm. Res. IJPR"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0140-6736(21)01825-0","article-title":"Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial","volume":"399","author":"Consortia","year":"2022","journal-title":"Lancet"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Bedoui, Y., Septembre-Malaterre, A., Giry, C., Jaffar-Bandjee, M.C., Selambarom, J., Guiraud, P., and Gasque, P. (2021). Robust COX-2-mediated prostaglandin response may drive arthralgia and bone destruction in patients with chronic inflammation post-chikungunya. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009115"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Lehman, C.W., Smith, A., Kelly, J., Jacobs, J.L., Dinman, J.D., and Kehn-Hall, K. (2022). EGR1 Upregulation during Encephalitic Viral Infections Contributes to Inflammation and Cell Death. Viruses, 14.","DOI":"10.3390\/v14061210"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0140-6736(22)01109-6","article-title":"Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial and updated meta-analysis","volume":"400","author":"Consortia","year":"2022","journal-title":"Lancet"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1097\/BOR.0b013e32835fd828","article-title":"Small molecular compounds in development for rheumatoid arthritis","volume":"25","year":"2013","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nrd.2017.267","article-title":"JAK inhibition as a therapeutic strategy for immune and inflammatory diseases","volume":"17","author":"Schwartz","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"114690","DOI":"10.1016\/j.bcp.2021.114690","article-title":"The JAK1\/2 inhibitor baricitinib suppresses eosinophil effector function and restricts allergen-induced airway eosinophilia","volume":"192","author":"Luschnig","year":"2021","journal-title":"Biochem. Pharmacol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/6\/1307\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:46:42Z","timestamp":1760125602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/6\/1307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,31]]},"references-count":63,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["v15061307"],"URL":"https:\/\/doi.org\/10.3390\/v15061307","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,31]]}}}