{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:01:12Z","timestamp":1781820072816,"version":"3.54.5"},"reference-count":108,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the \u201c2nd Call for H.F.R.I. Research Projects to Support Faculty Members &amp; Re-searchers\u201d","award":["03609"],"award-info":[{"award-number":["03609"]}]},{"name":"State Scholarships Foundation (IKY)","award":["03609"],"award-info":[{"award-number":["03609"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Subgenomic flaviviral RNAs (sfRNAs) are small non-coding products of the incomplete degradation of viral genomic RNA. They accumulate during flaviviral infection and have been associated with many functional roles inside the host cell. Studies so far have demonstrated that sfRNA plays a crucial role in determining West Nile virus (WNV) pathogenicity. However, its modulatory role on neuronal homeostasis has not been studied in depth. In this study, we investigated the mechanism of sfRNA biosynthesis and its importance for WNV replication in neuronal cells. We found that sfRNA1 is functionally redundant for both replication and translation of WNV. However, the concurrent absence of sfRNA1 and sfRNA2 species is detrimental for the survival of the virus. Differential expression analysis on RNA-seq data from WT and \u0394sfRNA replicon cell lines revealed transcriptional changes induced by sfRNA and identified a number of putative targets. Overall, it was shown that sfRNA contributes to the viral evasion by suppressing the interferon-mediated antiviral response. An additional differential expression analysis among replicon and control Neuro2A cells also clarified the transcriptional changes that support WNV replication in neuronal cells. Increased levels of translation and oxidative phosphorylation, post-translational modification processes, and activated DNA repair pathways were observed in replicon cell lines, while developmental processes such as axonal growth were deficient.<\/jats:p>","DOI":"10.3390\/v16050812","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T03:26:27Z","timestamp":1716261987000},"page":"812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["West Nile Virus Subgenomic RNAs Modulate Gene Expression in a Neuronal Cell Line"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9995-8283","authenticated-orcid":false,"given":"Maria","family":"Bampali","sequence":"first","affiliation":[{"name":"Laboratory of Biology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-2349","authenticated-orcid":false,"given":"Adamantia","family":"Kouvela","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3179-1066","authenticated-orcid":false,"given":"Nikolaos","family":"Kesesidis","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2235-8586","authenticated-orcid":false,"given":"Katerina","family":"Kassela","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3832-9939","authenticated-orcid":false,"given":"Nikolas","family":"Dovrolis","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3004-8104","authenticated-orcid":false,"given":"Ioannis","family":"Karakasiliotis","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-3670-0_1","article-title":"A Brief Review of West Nile Virus Biology","volume":"Volume 1435","author":"Colpitts","year":"2016","journal-title":"West Nile Virus: Methods and Protocols"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bampali, M., Konstantinidis, K., Kellis, E.E., Pouni, T., Mitroulis, I., Kottaridi, C., Mathioudakis, A.G., Beloukas, A., and Karakasiliotis, I. (2022). West Nile Disease Symptoms and Comorbidities: A Systematic Review and Analysis of Cases. Trop. Med. Infect. Dis., 7.","DOI":"10.3390\/tropicalmed7090236"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chancey, C., Grinev, A., Volkova, E., and Rios, M. (2015). The Global Ecology and Epidemiology of West Nile Virus. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/376230"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1017\/S0950268818000687","article-title":"Morbidity, Mortality and Long-Term Sequelae of West Nile Virus Disease in Qu\u00e9bec","volume":"146","author":"Ouhoumanne","year":"2018","journal-title":"Epidemiol. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gwon, Y.-D., Strand, M., Lindqvist, R., Nilsson, E., Saleeb, M., Elofsson, M., \u00d6verby, A.K., and Evander, M. (2020). Antiviral Activity of Benzavir-2 against Emerging Flaviviruses. Viruses, 12.","DOI":"10.3390\/v12030351"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ronca, S.E., Ruff, J.C., and Murray, K.O. (2021). A 20-Year Historical Review of West Nile Virus since Its Initial Emergence in North America: Has West Nile Virus Become a Neglected Tropical Disease?. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009190"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ng, W.C., Soto-Acosta, R., Bradrick, S.S., Garcia-Blanco, M.A., and Ooi, E.E. (2017). The 5\u2019 and 3\u2019 Untranslated Regions of the Flaviviral Genome. Viruses, 9.","DOI":"10.3390\/v9060137"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2092","DOI":"10.1002\/rmv.2092","article-title":"Structure and Function of Cis-Acting RNA Elements of Flavivirus","volume":"30","author":"Liu","year":"2020","journal-title":"Rev. Med. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1021\/acs.chemrev.7b00719","article-title":"Biochemistry and Molecular Biology of Flaviviruses","volume":"118","author":"Barrows","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"199340","DOI":"10.1016\/j.virusres.2024.199340","article-title":"Recruitment of the 40S Ribosomal Subunit by the West Nile Virus 3\u2019 UTR Promotes the Cross-Talk between the Viral Genomic Ends for Translation Regulation","volume":"343","year":"2024","journal-title":"Virus Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.tim.2016.01.002","article-title":"RNA Structure Duplications and Flavivirus Host Adaptation","volume":"24","author":"Villordo","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Villordo, S.M., Filomatori, C.V., S\u00e1nchez-Vargas, I., Blair, C.D., and Gamarnik, A.V. (2015). Dengue Virus RNA Structure Specialization Facilitates Host Adaptation. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004604"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Romero-L\u00f3pez, C., Roda-Herreros, M., Berzal-Herranz, B., Ramos-Lorente, S.E., and Berzal-Herranz, A. (2023). Inter- and Intramolecular RNA-RNA Interactions Modulate the Regulation of Translation Mediated by the 3\u2019 UTR in West Nile Virus. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065337"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41467-017-02604-y","article-title":"Mechanism and Structural Diversity of Exoribonuclease-Resistant RNA Structures in Flaviviral RNAs","volume":"9","author":"MacFadden","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.antiviral.2018.09.006","article-title":"Subgenomic Flaviviral RNAs: What Do We Know after the First Decade of Research","volume":"159","author":"Slonchak","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.chom.2008.10.007","article-title":"A Highly Structured, Nuclease-Resistant, Noncoding RNA Produced by Flaviviruses Is Required for Pathogenicity","volume":"4","author":"Pijlman","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11407","DOI":"10.1128\/JVI.01159-10","article-title":"RNA Structures Required for Production of Subgenomic Flavivirus RNA","volume":"84","author":"Funk","year":"2010","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.vetmic.2013.04.026","article-title":"Japanese Encephalitis Virus Non-Coding RNA Inhibits Activation of Interferon by Blocking Nuclear Translocation of Interferon Regulatory Factor 3","volume":"166","author":"Chang","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bidet, K., Dadlani, D., and Garcia-Blanco, M.A. (2014). G3BP1, G3BP2 and CAPRIN1 Are Required for Translation of Interferon Stimulated mRNAs and Are Targeted by a Dengue Virus Non-Coding RNA. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004242"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1126\/science.aab3369","article-title":"Dengue Subgenomic RNA Binds TRIM25 to Inhibit Interferon Expression for Epidemiological Fitness","volume":"350","author":"Manokaran","year":"2015","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.coviro.2015.10.001","article-title":"Arbovirus-Mosquito Interactions: RNAi Pathway","volume":"15","author":"Olson","year":"2015","journal-title":"Curr. Opin. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13486","DOI":"10.1128\/JVI.01104-12","article-title":"Noncoding Flavivirus RNA Displays RNA Interference Suppressor Activity in Insect and Mammalian Cells","volume":"86","author":"Schnettler","year":"2012","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.virol.2005.10.030","article-title":"A Rapid and Quantitative Assay for Measuring Antibody-Mediated Neutralization of West Nile Virus Infection","volume":"346","author":"Pierson","year":"2006","journal-title":"Virology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e01892","DOI":"10.7554\/eLife.01892","article-title":"RNA Structures That Resist Degradation by Xrn1 Produce a Pathogenic Dengue Virus RNA","volume":"3","author":"Chapman","year":"2014","journal-title":"eLife"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D792","DOI":"10.1093\/nar\/gkp1005","article-title":"PrimerBank: A Resource of Human and Mouse PCR Primer Pairs for Gene Expression Detection and Quantification","volume":"38","author":"Spandidos","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_26","unstructured":"Li, H. (2013). Aligning Sequence Reads, Clone Sequences and Assembly Contigs with BWA-MEM. arXiv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"1000 Genome Project Data Processing Subgroup The Sequence Alignment\/Map Format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative Genomics Viewer (IGV): High-Performance Genomics Data Visualization and Exploration","volume":"14","author":"Robinson","year":"2013","journal-title":"Brief. Bioinform."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon Provides Fast and Bias-Aware Quantification of Transcript Expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_30","unstructured":"(2023, June 06). R Core Team. R: A Language and Environment for Statistical Computing; R Foundation for Statistical Computing, Vienna, Austria. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.12688\/f1000research.7563.1","article-title":"Differential Analyses for RNA-Seq: Transcript-Level Estimates Improve Gene-Level Inferences","volume":"4","author":"Soneson","year":"2015","journal-title":"F1000Research"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fabregat, A., Sidiropoulos, K., Viteri, G., Forner, O., Marin-Garcia, P., Arnau, V., D\u2019Eustachio, P., Stein, L., and Hermjakob, H. (2017). Reactome Pathway Analysis: A High-Performance in-Memory Approach. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1559-2"},{"key":"ref_34","first-page":"100141","article-title":"clusterProfiler 4.0: A Universal Enrichment Tool for Interpreting Omics Data","volume":"2","author":"Wu","year":"2021","journal-title":"Innov. Camb. Mass"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9169146","DOI":"10.1155\/2017\/9169146","article-title":"Differential Alterations of the Mitochondrial Morphology and Respiratory Chain Complexes during Postnatal Development of the Mouse Lung","volume":"2017","author":"Pilatz","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_36","unstructured":"Hierholzer, J.C., and Killington, R.A. (1996). Virology Methods Manual, Elsevier."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jinf.2021.12.004","article-title":"MAMDC2, a Gene Highly Expressed in Microglia in Experimental Models of Alzheimers Disease, Positively Regulates the Innate Antiviral Response during Neurotropic Virus Infection","volume":"84","author":"Wang","year":"2022","journal-title":"J. Infect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.neuron.2011.05.029","article-title":"Ank3-Dependent SVZ Niche Assembly Is Required for the Continued Production of New Neurons","volume":"71","author":"Abdi","year":"2011","journal-title":"Neuron"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/ng.209","article-title":"Collaborative Genome-Wide Association Analysis Supports a Role for ANK3 and CACNA1C in Bipolar Disorder","volume":"40","author":"Ferreira","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8262","DOI":"10.1128\/JVI.00226-08","article-title":"West Nile Virus Nonstructural Protein 1 Inhibits TLR3 Signal Transduction","volume":"82","author":"Wilson","year":"2008","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12225","DOI":"10.1128\/JVI.78.22.12225-12235.2004","article-title":"Analysis of Adaptive Mutations in Kunjin Virus Replicon RNA Reveals a Novel Role for the Flavivirus Nonstructural Protein NS2A in Inhibition of Beta Interferon Promoter-Driven Transcription","volume":"78","author":"Liu","year":"2004","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1128\/JVI.01161-09","article-title":"The NS5 Protein of the Virulent West Nile Virus NY99 Strain Is a Potent Antagonist of Type I Interferon-Mediated JAK-STAT Signaling","volume":"84","author":"Boer","year":"2010","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5708","DOI":"10.1128\/JVI.00207-12","article-title":"West Nile Virus Noncoding Subgenomic RNA Contributes to Viral Evasion of the Type I Interferon-Mediated Antiviral Response","volume":"86","author":"Schuessler","year":"2012","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e01175-19","DOI":"10.1128\/JVI.01175-19","article-title":"Short Direct Repeats in the 3\u2019 Untranslated Region Are Involved in Subgenomic Flaviviral RNA Production","volume":"94","author":"Zhang","year":"2020","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10145","DOI":"10.1128\/JVI.00930-16","article-title":"Noncoding Subgenomic Flavivirus RNA Is Processed by the Mosquito RNA Interference Machinery and Determines West Nile Virus Transmission by Culex Pipiens Mosquitoes","volume":"90","author":"Fros","year":"2016","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1042\/BJ20140456","article-title":"Flaviviral RNAs: Weapons and Targets in the War between Virus and Host","volume":"462","author":"Bidet","year":"2014","journal-title":"Biochem. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.virol.2013.09.016","article-title":"Dengue Virus Subgenomic RNA Induces Apoptosis through the Bcl-2-Mediated PI3k\/Akt Signaling Pathway","volume":"448","author":"Liu","year":"2014","journal-title":"Virology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11395","DOI":"10.1128\/JVI.01047-10","article-title":"An RNA Pseudoknot Is Required for Production of Yellow Fever Virus Subgenomic RNA by the Host Nuclease XRN1","volume":"84","author":"Silva","year":"2010","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/s41467-022-28977-3","article-title":"Structural Analysis of 3\u2019UTRs in Insect Flaviviruses Reveals Novel Determinants of sfRNA Biogenesis and Provides New Insights into Flavivirus Evolution","volume":"13","author":"Slonchak","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1038\/s41467-020-16086-y","article-title":"Zika Virus Noncoding RNA Suppresses Apoptosis and Is Required for Virus Transmission by Mosquitoes","volume":"11","author":"Slonchak","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eadd8095","DOI":"10.1126\/sciadv.add8095","article-title":"Zika Virus Noncoding RNA Cooperates with the Viral Protein NS5 to Inhibit STAT1 Phosphorylation and Facilitate Viral Pathogenesis","volume":"8","author":"Slonchak","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tremblay, N., Freppel, W., Sow, A.A., and Chatel-Chaix, L. (2019). The Interplay between Dengue Virus and the Human Innate Immune System: A Game of Hide and Seek. Vaccines, 7.","DOI":"10.3390\/vaccines7040145"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Donald, C.L., Brennan, B., Cumberworth, S.L., Rezelj, V.V., Clark, J.J., Cordeiro, M.T., Freitas De Oliveira Fran\u00e7a, R., Pena, L.J., Wilkie, G.S., and Da Silva Filipe, A. (2016). Full Genome Sequence and sfRNA Interferon Antagonist Activity of Zika Virus from Recife, Brazil. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0005048"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Slonchak, A., Chaggar, H., Aguado, J., Wolvetang, E., and Khromykh, A.A. (2023). Noncoding RNA of Zika Virus Affects Interplay between Wnt-Signaling and Pro-Apoptotic Pathways in the Developing Brain Tissue. Viruses, 15.","DOI":"10.3390\/v15051062"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.chom.2015.07.009","article-title":"Dengue Non-Coding RNA: TRIMmed for Transmission","volume":"18","author":"Pijlman","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101979","DOI":"10.1016\/j.npep.2019.101979","article-title":"Overexpression of Neuropeptide Y Decreases Responsiveness to Neuropeptide Y","volume":"79","author":"Corder","year":"2020","journal-title":"Neuropeptides"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.npep.2012.09.001","article-title":"Multifaces of Neuropeptide Y in the Brain\u2014Neuroprotection, Neurogenesis and Neuroinflammation","volume":"46","author":"Malva","year":"2012","journal-title":"Neuropeptides"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"41921","DOI":"10.1074\/jbc.M110.164020","article-title":"Neuropeptide Y Modulation of Interleukin-1{\u03b2} (IL-1{\u03b2})-Induced Nitric Oxide Production in Microglia","volume":"285","author":"Ferreira","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.2174\/1570159X19666210906120302","article-title":"Neuroprotective Effects of Neuropeptide Y against Neurodegenerative Disease","volume":"20","author":"Pain","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1128\/JVI.02934-15","article-title":"Neuropeptide Y Negatively Influences Monocyte Recruitment to the Central Nervous System during Retrovirus Infection","volume":"90","author":"Woods","year":"2015","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11076","DOI":"10.1128\/JVI.01022-10","article-title":"Neuropeptide Y Has a Protective Role during Murine Retrovirus-Induced Neurological Disease","volume":"84","author":"Du","year":"2010","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/14712598.2018.1486817","article-title":"Anti-Inflammatory Potential of Thymosin \u03924 in the Central Nervous System: Implications for Progressive Neurodegenerative Diseases","volume":"18","author":"Pardon","year":"2018","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1517\/14712598.2015.1005596","article-title":"Thymosin \u03924 as a Restorative\/Regenerative Therapy for Neurological Injury and Neurodegenerative Diseases","volume":"15","author":"Chopp","year":"2015","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s12974-021-02166-3","article-title":"Thymosin \u03924 Reverses Phenotypic Polarization of Glial Cells and Cognitive Impairment via Negative Regulation of NF-\u03baB Signaling Axis in APP\/PS1 Mice","volume":"18","author":"Wang","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1007\/s11064-008-9712-y","article-title":"The Promotive Effects of Thymosin \u03924 on Neuronal Survival and Neurite Outgrowth by Upregulating L1 Expression","volume":"33","author":"Yang","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8721","DOI":"10.1128\/JVI.00144-10","article-title":"Virus-Induced Ca2+ Influx Extends Survival of West Nile Virus-Infected Cells","volume":"84","author":"Scherbik","year":"2010","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1016\/j.febslet.2015.06.041","article-title":"Calpain Mediates Processing of the Translation Termination Factor eRF3 into the IAP-Binding Isoform p-eRF3","volume":"589","author":"Hashimoto","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/cbin.10043","article-title":"Polypeptide Chain Release Factor eRF3 Is a Novel Molecular Partner of Survivin","volume":"37","author":"Xiao","year":"2013","journal-title":"Cell Biol. Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.bbrc.2014.02.063","article-title":"The Processed Isoform of the Translation Termination Factor eRF3 Localizes to the Nucleus to Interact with the ARF Tumor Suppressor","volume":"445","author":"Hashimoto","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1128\/JVI.79.1.380-392.2005","article-title":"Kissing-Loop Interaction in the 3\u2019 End of the Hepatitis C Virus Genome Essential for RNA Replication","volume":"79","author":"Friebe","year":"2005","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"629","DOI":"10.3201\/eid1104.041076","article-title":"Molecular Mechanisms of West Nile Virus Pathogenesis in Brain Cell","volume":"11","author":"Koh","year":"2005","journal-title":"Emerg. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e62273","DOI":"10.7554\/eLife.62273","article-title":"Virus Infection of the CNS Disrupts the Immune-Neural-Synaptic Axis via Induction of Pleiotropic Gene Regulation of Host Responses","volume":"10","author":"Maximova","year":"2021","journal-title":"eLife"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Lim, S.M., van den Ham, H.-J., Oduber, M., Martina, E., Zaaraoui-Boutahar, F., Roose, J.M., van IJcken, W.F.J., 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_74","doi-asserted-by":"crossref","first-page":"e00902","DOI":"10.1128\/mBio.00902-14","article-title":"Virus-Induced Transcriptional Changes in the Brain Include the Differential Expression of Genes Associated with Interferon, Apoptosis, Interleukin 17 Receptor A, and Glutamate Signaling as Well as Flavivirus-Specific Upregulation of tRNA Synthetases","volume":"5","author":"Clarke","year":"2014","journal-title":"mBio"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"26350","DOI":"10.1038\/srep26350","article-title":"Identification of Host Genes Leading to West Nile Virus Encephalitis in Mice Brain Using RNA-Seq Analysis","volume":"6","author":"Kumar","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1128\/JVI.02944-13","article-title":"Death Receptor-Mediated Apoptotic Signaling Is Activated in the Brain Following Infection with West Nile Virus in the Absence of a Peripheral Immune Response","volume":"88","author":"Clarke","year":"2014","journal-title":"J. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.virol.2005.07.013","article-title":"Gene Expression in Mice Infected with West Nile Virus Strains of Different Neurovirulence","volume":"342","author":"Venter","year":"2005","journal-title":"Virology"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Bourgeois, M.A., Denslow, N.D., Seino, K.S., Barber, D.S., and Long, M.T. (2011). Gene Expression Analysis in the Thalamus and Cerebrum of Horses Experimentally Infected with West Nile Virus. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024371"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"630","DOI":"10.3389\/fimmu.2016.00630","article-title":"Effects of Interferons and Viruses on Metabolism","volume":"7","author":"Fritsch","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1128\/JVI.02649-13","article-title":"Beta Interferon Regulation of Glucose Metabolism Is PI3K\/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3","volume":"88","author":"Burke","year":"2014","journal-title":"J. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.immuni.2016.06.006","article-title":"Type 1 Interferons Induce Changes in Core Metabolism That Are Critical for Immune Function","volume":"44","author":"Wu","year":"2016","journal-title":"Immunity"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4960","DOI":"10.1021\/pr100219y","article-title":"The Ubiquitin-Proteasome Pathway Is Important for Dengue Virus Infection in Primary Human Endothelial Cells","volume":"9","author":"Kanlaya","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.virol.2008.11.034","article-title":"West Nile Virus Genome Amplification Requires the Functional Activities of the Proteasome","volume":"385","author":"Gilfoy","year":"2009","journal-title":"Virology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1128\/JVI.02483-10","article-title":"Appraising the Roles of CBLL1 and the Ubiquitin\/Proteasome System for Flavivirus Entry and Replication","volume":"85","author":"Meertens","year":"2011","journal-title":"J. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.virusres.2012.01.009","article-title":"A Small-Molecule Inhibitor of Deubiquitinating Enzyme USP14 Inhibits Dengue Virus Replication","volume":"165","author":"Nag","year":"2012","journal-title":"Virus Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Basters, A., Knobeloch, K.-P., and Fritz, G. (2018). USP18\u2014A Multifunctional Component in the Interferon Response. Biosci. Rep., 38.","DOI":"10.1042\/BSR20180250"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Fran\u00e7ois-Newton, V., Magno de Freitas Almeida, G., Payelle-Brogard, B., Monneron, D., Pichard-Garcia, L., Piehler, J., Pellegrini, S., and Uz\u00e9, G. (2011). USP18-Based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon \u03b1 Response. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022200"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e2444","DOI":"10.1038\/cddis.2016.326","article-title":"Multiple Functions of USP18","volume":"7","author":"Honke","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Ye, H., Duan, X., Yao, M., Kang, L., Li, Y., Li, S., Li, B., and Chen, L. (2021). USP18 Mediates Interferon Resistance of Dengue Virus Infection. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.682380"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"19465","DOI":"10.1073\/pnas.2006492117","article-title":"RTP4 Inhibits IFN-I Response and Enhances Experimental Cerebral Malaria and Neuropathology","volume":"117","author":"He","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1002\/hep.24576","article-title":"Up-Regulation of Hedgehog Pathway Is Associated with Cellular Permissiveness for Hepatitis C Virus Replication","volume":"54","author":"Choi","year":"2011","journal-title":"Hepatology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1080\/15548627.2015.1037062","article-title":"Reconciling West Nile Virus with the Autophagic Pathway","volume":"11","author":"Saiz","year":"2015","journal-title":"Autophagy"},{"key":"ref_93","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_94","doi-asserted-by":"crossref","unstructured":"B\u0119bnowska, D., and Nied\u017awiedzka-Rystwej, P. (2022). The Interplay between Autophagy and Virus Pathogenesis\u2014The Significance of Autophagy in Viral Hepatitis and Viral Hemorrhagic Fevers. Cells, 11.","DOI":"10.3390\/cells11050871"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.virol.2012.08.016","article-title":"West Nile Virus Growth Is Independent of Autophagy Activation","volume":"433","author":"Beatman","year":"2012","journal-title":"Virology"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Vandergaast, R., and Fredericksen, B.L. (2012). West Nile Virus (WNV) Replication Is Independent of Autophagy in Mammalian Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045800"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Kobayashi, S., Yoshii, K., Phongphaew, W., Muto, M., Hirano, M., Orba, Y., Sawa, H., and Kariwa, H. (2020). West Nile Virus Capsid Protein Inhibits Autophagy by AMP-Activated Protein Kinase Degradation in Neurological Disease Development. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008238"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"9458","DOI":"10.1128\/JVI.01323-14","article-title":"West Nile Virus-Induced Activation of Mammalian Target of Rapamycin Complex 1 Supports Viral Growth and Viral Protein Expression","volume":"88","author":"Shives","year":"2014","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"8388","DOI":"10.1128\/JVI.79.13.8388-8399.2005","article-title":"Flavivirus Activates Phosphatidylinositol 3-Kinase Signaling to Block Caspase-Dependent Apoptotic Cell Death at the Early Stage of Virus Infection","volume":"79","author":"Lee","year":"2005","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Le Sage, V., Cinti, A., Amorim, R., and Mouland, A.J. (2016). Adapting the Stress Response: Viral Subversion of the mTOR Signaling Pathway. Viruses, 8.","DOI":"10.3390\/v8060152"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4161\/cc.22912","article-title":"mTORC1 and P53: Clash of the Gods?","volume":"12","author":"Hasty","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.tcb.2010.03.004","article-title":"The Regulation of Energy Metabolism and the IGF-1\/mTOR Pathways by the P53 Protein","volume":"20","author":"Feng","year":"2010","journal-title":"Trends Cell Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1007\/s12035-018-1263-x","article-title":"Zika Virus and the Metabolism of Neuronal Cells","volume":"56","author":"Rothan","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Cui, D., Qu, R., Liu, D., Xiong, X., Liang, T., and Zhao, Y. (2021). The Cross Talk Between P53 and mTOR Pathways in Response to Physiological and Genotoxic Stresses. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.775507"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Fraisier, C., Camoin, L., Lim, S.M., Bakli, M., Belghazi, M., Fourquet, P., Granjeaud, S., Osterhaus, A.D.M.E., Koraka, P., and Martina, B. (2013). Altered Protein Networks and Cellular Pathways in Severe West Nile Disease in Mice. PLoS ONE, 8.","DOI":"10.1371\/annotation\/a01d68f4-f23d-4c0a-a0f8-f32432b0efa7"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Huang, B., West, N., Vider, J., Zhang, P., Griffiths, R.E., Wolvetang, E., Burtonclay, P., and Warrilow, D. (2019). Inflammatory Responses to a Pathogenic West Nile Virus Strain. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4471-8"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1523\/JNEUROSCI.4889-04.2005","article-title":"Ca2+-Dependent Regulation of Rho GTPases Triggers Turning of Nerve Growth Cones","volume":"25","author":"Jin","year":"2005","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nn1869","article-title":"Rho Mediates Calcium-Dependent Activation of P38alpha and Subsequent Excitotoxic Cell Death","volume":"10","author":"Semenova","year":"2007","journal-title":"Nat. Neurosci."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/5\/812\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:45:20Z","timestamp":1760107520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/5\/812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,20]]},"references-count":108,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["v16050812"],"URL":"https:\/\/doi.org\/10.3390\/v16050812","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,20]]}}}