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Many RNA viruses, particularly flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), and Japanese encephalitis virus (JEV), extensively remodel the ER to establish replication compartments and assemble progeny virions. This massive reorganization disrupts ER homeostasis, leading to UPR activation. Emerging evidence reveals that flaviviruses not only trigger but also manipulate the three UPR branches\u2014PERK, IRE1, and ATF6\u2014to optimize viral translation, replication, and egress. In parallel, flavivirus infection profoundly alters host lipid metabolism and promotes dynamic changes in lipid droplets (LDs), key organelles that mediate lipid storage and serve as scaffolds for viral replication and assembly. The UPR intimately connects to LD biogenesis through transcriptional and translational programs mediated by XBP1, ATF4, and ATF6, thereby coupling ER stress responses to lipid remodeling and energy homeostasis. This intricate crosstalk between UPR and LDs creates a metabolic and structural niche favorable for viral replication but detrimental to host cell integrity. This review provides a comprehensive analysis of the molecular mechanisms by which flaviviruses exploit ER stress and the UPR to reprogram lipid metabolism and LD dynamics. We highlight the dual role of UPR signaling in promoting adaptive lipid synthesis and initiating cell death under prolonged stress, discuss recent insights into ER\u2013LD interactions during flavivirus infection, and explore therapeutic opportunities targeting UPR\u2013lipid metabolic pathways as broad-spectrum antiviral strategies. Understanding this interconnected network will advance our knowledge of viral pathogenesis and identify new avenues for host-directed antiviral intervention.<\/jats:p>","DOI":"10.3390\/v18050493","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:08:02Z","timestamp":1777018082000},"page":"493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Flavivirus-Induced ER Stress and Unfolded Protein Response: A Central Hub Linking Lipid Droplet Remodeling and Viral Replication"],"prefix":"10.3390","volume":"18","author":[{"given":"Imaan","family":"Muhammad","sequence":"first","affiliation":[{"name":"Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaci","family":"Craft","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaokai","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Cruz-Cosme","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6487-2356","authenticated-orcid":false,"given":"Qiyi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.3390\/v7041927","article-title":"Insect-specific flaviviruses: A systematic review of their discovery, host range, mode of transmission, superinfection exclusion potential and genomic organization","volume":"7","author":"Blitvich","year":"2015","journal-title":"Viruses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrmicro1067","article-title":"A structural perspective of the flavivirus life cycle","volume":"3","author":"Mukhopadhyay","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.coviro.2012.02.011","article-title":"Degrees of maturity: The complex structure and biology of flaviviruses","volume":"2","author":"Pierson","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"van den Elsen, K., Quek, J.P., and Luo, D. (2021). Molecular Insights into the Flavivirus Replication Complex. Viruses, 13.","DOI":"10.3390\/v13060956"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Brand, C., Bisaillon, M., and Geiss, B.J. (2017). Organization of the Flavivirus RNA replicase complex. Wiley Interdiscip. Rev. RNA, 8.","DOI":"10.1002\/wrna.1437"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wong, H.H., Crudgington, D.R.K., Siu, L., and Sanyal, S. (2024). Flaviviruses induce ER-specific remodelling of protein synthesis. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012766"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/B978-0-12-385114-7.00004-0","article-title":"Measuring ER stress and the unfolded protein response using mammalian tissue culture system","volume":"490","author":"Oslowski","year":"2011","journal-title":"Methods Enzymol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/febs.14608","article-title":"Endoplasmic reticulum stress signalling\u2014From basic mechanisms to clinical applications","volume":"286","author":"Almanza","year":"2019","journal-title":"FEBS J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"114463","DOI":"10.1016\/j.yexcr.2025.114463","article-title":"Endoplasmic reticulum stress and unfolded protein response in renal lipid metabolism","volume":"446","author":"Zhou","year":"2025","journal-title":"Exp. Cell Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Read, A., and Schroder, M. (2021). The Unfolded Protein Response: An Overview. Biology, 10.","DOI":"10.3390\/biology10050384"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2438-7_1","article-title":"Coronaviruses: An overview of their replication and pathogenesis","volume":"1282","author":"Fehr","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-0716-0900-2_1","article-title":"Coronaviruses: An Updated Overview of Their Replication and Pathogenesis","volume":"2203","author":"Wang","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10849","DOI":"10.1128\/JVI.01151-07","article-title":"West Nile virus infection activates the unfolded protein response, leading to CHOP induction and apoptosis","volume":"81","author":"Medigeshi","year":"2007","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.virol.2009.06.039","article-title":"Hepatitis C virus NS4B induces unfolded protein response and endoplasmic reticulum overload response-dependent NF-kappaB activation","volume":"391","author":"Li","year":"2009","journal-title":"Virology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"14226","DOI":"10.1074\/jbc.M111.222703","article-title":"Dengue virus modulates the unfolded protein response in a time-dependent manner","volume":"286","author":"Pena","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1099\/jgv.0.000792","article-title":"Japanese encephalitis virus activates autophagy through XBP1 and ATF6 ER stress sensors in neuronal cells","volume":"98","author":"Sharma","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1186\/s12974-018-1311-5","article-title":"ZIKV infection activates the IRE1-XBP1 and ATF6 pathways of unfolded protein response in neural cells","volume":"15","author":"Tan","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mufrrih, M., Chen, B., and Chan, S.W. (2021). Zika Virus Induces an Atypical Tripartite Unfolded Protein Response with Sustained Sensor and Transient Effector Activation and a Blunted BiP Response. mSphere, 6.","DOI":"10.1128\/mSphere.00876-21"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chen, Q., Fang, W., Cui, K., Chen, Q., Xiang, X., Zhang, J., Zhang, Y., Mai, K., and Ai, Q. (2021). Endoplasmic reticulum stress induces hepatic steatosis by transcriptional upregulating lipid droplet protein perilipin2. FASEB J., 35.","DOI":"10.1096\/fj.202100739RR"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1091\/mbc.e16-10-0717","article-title":"Phospholipase Lpl1 links lipid droplet function with quality control protein degradation","volume":"28","author":"Weisshaar","year":"2017","journal-title":"Mol. Biol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hsia, J.Z., Liu, D., Haynes, L., Cruz-Cosme, R., and Tang, Q. (2024). Lipid Droplets: Formation, Degradation, and Their Role in Cellular Responses to Flavivirus Infections. Microorganisms, 12.","DOI":"10.3390\/microorganisms12040647"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.chom.2018.05.005","article-title":"Flaviviruses Exploit the Lipid Droplet Protein AUP1 to Trigger Lipophagy and Drive Virus Production","volume":"23","author":"Zhang","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s44298-024-00031-7","article-title":"The endoplasmic reticulum (ER): A crucial cellular hub in flavivirus infection and potential target site for antiviral interventions","volume":"2","author":"Verhaegen","year":"2024","journal-title":"npj Viruses"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Figueroa-Juarez, E., Noriega, L.G., Perez-Monter, C., Aleman, G., Hernandez-Pando, R., Correa-Rotter, R., Ramirez, V., Tovar, A.R., Torre-Villalvazo, I., and Tovar-Palacio, C. (2021). The Role of the Unfolded Protein Response on Renal Lipogenesis in C57BL\/6 Mice. Biomolecules, 11.","DOI":"10.3390\/biom11010073"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"203","DOI":"10.4254\/wjh.v2.i6.203","article-title":"Role of unfolded protein response in lipogenesis","volume":"2","author":"Zheng","year":"2010","journal-title":"World J. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Angara, R.K., Sladek, M.F., and Gilk, S.D. (2024). ER-LD Membrane Contact Sites: A Budding Area in the Pathogen Survival Strategy. Contact, 7.","DOI":"10.1177\/25152564241304196"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sorouri, M., Chang, T., and Hancks, D.C. (2022). Mitochondria and Viral Infection: Advances and Emerging Battlefronts. mBio, 13.","DOI":"10.1128\/mbio.02096-21"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev-pathol-012513-104649","article-title":"The role of endoplasmic reticulum stress in human pathology","volume":"10","author":"Oakes","year":"2015","journal-title":"Annu. Rev. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102061","DOI":"10.1016\/j.jbc.2022.102061","article-title":"Regulation of calcium homeostasis and flux between the endoplasmic reticulum and the cytosol","volume":"298","author":"Prols","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1007\/s11033-022-08065-x","article-title":"Progesterone regulates the endoplasmic reticulum-associated degradation and Unfolded Protein Response axis by mimicking the androgenic stimulation in prostate cancer cells","volume":"50","author":"Erzurumlu","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1177\/1947601910383011","article-title":"The Unfolded Protein Response, Degradation from Endoplasmic Reticulum and Cancer","volume":"1","author":"Tsai","year":"2010","journal-title":"Genes Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.4103\/1673-5374.393105","article-title":"The physiological role of the unfolded protein response in the nervous system","volume":"19","author":"Wu","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Braakman, I., and Hebert, D.N. (2013). Protein folding in the endoplasmic reticulum. Cold Spring Harb. Perspect. Biol., 5.","DOI":"10.1101\/cshperspect.a013201"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5343","DOI":"10.1007\/s00216-015-8694-2","article-title":"Identification of known drugs targeting the endoplasmic reticulum stress response","volume":"407","author":"Bi","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1091\/mbc.e13-09-0511","article-title":"Interaction of Nck1 and PERK phosphorylated at Y561 negatively modulates PERK activity and PERK regulation of pancreatic beta-cell proinsulin content","volume":"25","author":"Yamani","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wek, R.C. (2018). Role of eIF2alpha Kinases in Translational Control and Adaptation to Cellular Stress. Cold Spring Harb. Perspect. Biol., 10.","DOI":"10.1101\/cshperspect.a032870"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Neill, G., and Masson, G.R. (2023). A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1112253"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tem.2009.05.008","article-title":"ATF4-dependent transcription mediates signaling of amino acid limitation","volume":"20","author":"Kilberg","year":"2009","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"35106","DOI":"10.1074\/jbc.M806874200","article-title":"C\/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene","volume":"283","author":"Su","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12985-020-01362-6","article-title":"The role of host eIF2alpha in viral infection","volume":"17","author":"Liu","year":"2020","journal-title":"Virol. J."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Guan, Y., Wang, Y., Fu, X., Bai, G., Li, X., Mao, J., Yan, Y., and Hu, L. (2023). Multiple functions of stress granules in viral infection at a glance. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1138864"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Luo, X., Alfason, L., Wei, M., Wu, S., and Kasim, V. (2022). Spliced or Unspliced, That Is the Question: The Biological Roles of XBP1 Isoforms in Pathophysiology. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052746"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Park, S.M., Kang, T.I., and So, J.S. (2021). Roles of XBP1s in Transcriptional Regulation of Target Genes. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070791"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/cbin.11533","article-title":"X-box binding protein 1 (XBP1) function in diseases","volume":"45","author":"Xu","year":"2021","journal-title":"Cell Biol. Int."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Han, S. (2025). Stress, plasticity, and fibrosis: Unfolding the role of the IRE1alpha\/RIDD\/Fgfr2 axis. J. Clin. Investig., 135.","DOI":"10.1172\/JCI196740"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/S1097-2765(00)00133-7","article-title":"ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs","volume":"6","author":"Ye","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lei, Y., Yu, H., Ding, S., Liu, H., Liu, C., and Fu, R. (2024). Molecular mechanism of ATF6 in unfolded protein response and its role in disease. Heliyon, 10.","DOI":"10.1016\/j.heliyon.2024.e25937"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S1534-5807(02)00203-4","article-title":"ER stress regulation of ATF6 localization by dissociation of BiP\/GRP78 binding and unmasking of Golgi localization signals","volume":"3","author":"Shen","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Shen, Y., Li, R., Yu, S., Zhao, Q., Wang, Z., Sheng, H., and Yang, W. (2021). Activation of the ATF6 (Activating Transcription Factor 6) Signaling Pathway in Neurons Improves Outcome After Cardiac Arrest in Mice. J. Am. Heart Assoc., 10.","DOI":"10.1161\/JAHA.120.020216"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s12250-019-00131-2","article-title":"Proteomics Profiling of Host Cell Response via Protein Expression and Phosphorylation upon Dengue Virus Infection","volume":"34","author":"Miao","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12929-020-0618-6","article-title":"Endoplasmic reticulum: A focal point of Zika virus infection","volume":"27","author":"Khazali","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tian, J.N., Yang, C.C., Chuang, C.K., Tsai, M.H., Wu, R.H., Chen, C.T., and Yueh, A. (2019). A Dengue Virus Type 2 (DENV-2) NS4B-Interacting Host Factor, SERP1, Reduces DENV-2 Production by Suppressing Viral RNA Replication. Viruses, 11.","DOI":"10.3390\/v11090787"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8226","DOI":"10.4049\/jimmunol.175.12.8226","article-title":"E2 of hepatitis C virus inhibits apoptosis","volume":"175","author":"Lee","year":"2005","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1515\/revneuro-2017-0071","article-title":"Mechanisms of disordered neurodegenerative function: Concepts and facts about the different roles of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)","volume":"29","author":"Taalab","year":"2018","journal-title":"Rev. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zhao, N., Li, N., and Wang, T. (2023). PERK prevents rhodopsin degradation during retinitis pigmentosa by inhibiting IRE1-induced autophagy. J. Cell Biol., 222.","DOI":"10.1083\/jcb.202208147"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1091\/mbc.E17-10-0594","article-title":"Dynamic changes in complexes of IRE1alpha, PERK, and ATF6alpha during endoplasmic reticulum stress","volume":"29","author":"Sundaram","year":"2018","journal-title":"Mol. Biol. Cell"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Blazquez, A.B., Escribano-Romero, E., Merino-Ramos, T., Saiz, J.C., and Martin-Acebes, M.A. (2014). Stress responses in flavivirus-infected cells: Activation of unfolded protein response and autophagy. Front. Microbiol., 5.","DOI":"10.3389\/fmicb.2014.00266"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5501\/wjv.v6.i1.1","article-title":"Biological and historical overview of Zika virus","volume":"6","author":"Armstrong","year":"2017","journal-title":"World J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Vue, D., and Tang, Q. (2021). Zika Virus Overview: Transmission, Origin, Pathogenesis, Animal Model and Diagnosis. Zoonoses, 1.","DOI":"10.15212\/ZOONOSES-2021-0017"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.gene.2017.07.049","article-title":"Molecular cloning and characterization of the genes encoding the proteins of Zika virus","volume":"628","author":"Hou","year":"2017","journal-title":"Gene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.mib.2016.05.003","article-title":"(+) RNA virus replication compartments: A safe home for (most) viral replication","volume":"32","author":"Shulla","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00018-022-04469-x","article-title":"The double-membrane vesicle (DMV): A virus-induced organelle dedicated to the replication of SARS-CoV-2 and other positive-sense single-stranded RNA viruses","volume":"79","author":"Roingeard","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.coviro.2011.09.008","article-title":"Virus factories, double membrane vesicles and viroplasm generated in animal cells","volume":"1","author":"Netherton","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.biochi.2020.05.011","article-title":"Zika virus subversion of chaperone GRP78\/BiP expression in A549 cells during UPR activation","volume":"175","author":"Turpin","year":"2020","journal-title":"Biochimie"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Oyarzun-Arrau, A., Alonso-Palomares, L., Valiente-Echeverria, F., Osorio, F., and Soto-Rifo, R. (2020). Crosstalk between RNA Metabolism and Cellular Stress Responses during Zika Virus Replication. Pathogens, 9.","DOI":"10.3390\/pathogens9030158"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hou, S., Kumar, A., Xu, Z., Airo, A.M., Stryapunina, I., Wong, C.P., Branton, W., Tchesnokov, E., Gotte, M., and Power, C. (2017). Zika virus hijacks stress granule proteins and modulates the host stress response. J. Virol., 91.","DOI":"10.1128\/JVI.00474-17"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1021\/acsinfecdis.9b00526","article-title":"Targeting the Inositol-Requiring Enzyme-1 Pathway Efficiently Reverts Zika Virus-Induced Neurogenesis and Spermatogenesis Marker Perturbations","volume":"6","author":"Chu","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Huang, Y., Lin, Q., Huo, Z., Chen, C., Zhou, S., Ma, X., Gao, H., Lin, Y., Li, X., and He, J. (2020). Inositol-Requiring Enzyme 1alpha Promotes Zika Virus Infection through Regulation of Stearoyl Coenzyme A Desaturase 1-Mediated Lipid Metabolism. J. Virol., 94.","DOI":"10.1128\/JVI.01229-20"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.stem.2016.07.019","article-title":"Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy","volume":"19","author":"Liang","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kolpikova, E.P., Tronco, A.R., Hartigh, A.B.D., Jackson, K.J., Iwawaki, T., and Fink, S.L. (2020). IRE1alpha Promotes Zika Virus Infection via XBP1. Viruses, 12.","DOI":"10.3390\/v12030278"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Guzman-Rodriguez, M., Hernandez-Diaz, T., Lisboa, P., Lopez-Schettini, J., Sanhueza, S., Leyton, L., Iwawaki, T., Soto-Rifo, R., and Osorio, F. (2025). The IRE1\/XBP1s Axis Regulates Innate Immune Responses in Conventional Dendritic Cells During ZIKV Infection. FASEB J., 39.","DOI":"10.1096\/fj.202501186R"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Wu, X., Zhang, L., Liu, C., Cheng, Q., Zhao, W., Chen, P., Qin, Y., and Chen, M. (2024). The NS2B-PP1alpha-eIF2alpha axis: Inhibiting stress granule formation and Boosting Zika virus replication. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012355"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Blazquez, A.B., Martin-Acebes, M.A., Poderoso, T., and Saiz, J.C. (2021). Relevance of oxidative stress in inhibition of eIF2 alpha phosphorylation and stress granules formation during Usutu virus infection. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009072"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"11868","DOI":"10.1128\/JVI.00879-06","article-title":"Flavivirus infection activates the XBP1 pathway of the unfolded protein response to cope with endoplasmic reticulum stress","volume":"80","author":"Yu","year":"2006","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Datan, E., Roy, S.G., Germain, G., Zali, N., McLean, J.E., Golshan, G., Harbajan, S., Lockshin, R.A., and Zakeri, Z. (2016). Dengue-induced autophagy, virus replication and protection from cell death require ER stress (PERK) pathway activation. Cell Death Dis., 7.","DOI":"10.1038\/cddis.2015.409"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Reid, D.W., Campos, R.K., Child, J.R., Zheng, T., Chan, K.W.K., Bradrick, S.S., Vasudevan, S.G., Garcia-Blanco, M.A., and Nicchitta, C.V. (2018). Dengue Virus Selectively Annexes Endoplasmic Reticulum-Associated Translation Machinery as a Strategy for Co-opting Host Cell Protein Synthesis. J. Virol., 92.","DOI":"10.1128\/JVI.01766-17"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/s41598-017-18909-3","article-title":"Dengue virus-induced ER stress is required for autophagy activation, viral replication, and pathogenesis both in vitro and in vivo","volume":"8","author":"Lee","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Tabata, K., Arakawa, M., Ishida, K., Kobayashi, M., Nara, A., Sugimoto, T., Okada, T., Mori, K., and Morita, E. (2021). Endoplasmic Reticulum-Associated Degradation Controls Virus Protein Homeostasis, Which Is Required for Flavivirus Propagation. J. Virol., 95.","DOI":"10.1128\/JVI.02234-20"},{"key":"ref_79","first-page":"291","article-title":"BiP: Master Regulator of the Unfolded Protein Response and Crucial Factor in Flavivirus Biology","volume":"90","author":"Lewy","year":"2017","journal-title":"Yale J. Biol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Perera, N., Miller, J.L., and Zitzmann, N. (2017). The role of the unfolded protein response in dengue virus pathogenesis. Cell. Microbiol., 19.","DOI":"10.1111\/cmi.12734"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1093\/abbs\/gmv108","article-title":"Effect of modulation of unfolded protein response pathway on dengue virus infection","volume":"47","author":"Diwaker","year":"2015","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Thepparit, C., Khakpoor, A., Khongwichit, S., Wikan, N., Fongsaran, C., Chingsuwanrote, P., Panraksa, P., and Smith, D.R. (2013). Dengue 2 infection of HepG2 liver cells results in endoplasmic reticulum stress and induction of multiple pathways of cell death. BMC Res. Notes, 6.","DOI":"10.1186\/1756-0500-6-372"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.1038\/s41467-019-11663-2","article-title":"Viral priming of cell intrinsic innate antiviral signaling by the unfolded protein response","volume":"10","author":"Carletti","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.1128\/JVI.03453-14","article-title":"Characterization of dengue virus NS4A and NS4B protein interaction","volume":"89","author":"Zou","year":"2015","journal-title":"J. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Liu, H., Zhang, L., Sun, J., Chen, W., Li, S., Wang, Q., Yu, H., Xia, Z., Jin, X., and Wang, C. (2017). Endoplasmic Reticulum Protein SCAP Inhibits Dengue Virus NS2B3 Protease by Suppressing Its K27-Linked Polyubiquitylation. J. Virol., 91.","DOI":"10.1128\/JVI.02234-16"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Ci, Y., Liu, Z.Y., Zhang, N.N., Niu, Y., Yang, Y., Xu, C., Yang, W., Qin, C.F., and Shi, L. (2020). Zika NS1-induced ER remodeling is essential for viral replication. J. Cell Biol., 219.","DOI":"10.1083\/jcb.201903062"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1128\/JVI.02782-13","article-title":"Dimerization of flavivirus NS4B protein","volume":"88","author":"Zou","year":"2014","journal-title":"J. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Almasy, K.M., Davies, J.P., Lisy, S.M., Tirgar, R., Tran, S.C., and Plate, L. (2021). Small-molecule endoplasmic reticulum proteostasis regulator acts as a broad-spectrum inhibitor of dengue and Zika virus infections. Proc. Natl. Acad. Sci. USA, 118.","DOI":"10.1073\/pnas.2012209118"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1042\/BSR20100078","article-title":"Unfolded protein response (UPR) gene expression during antibody-dependent enhanced infection of cultured monocytes correlates with dengue disease severity","volume":"31","author":"Paradkar","year":"2011","journal-title":"Biosci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.antiviral.2011.10.002","article-title":"Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model","volume":"92","author":"Rathore","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/1743-422X-4-91","article-title":"Dengue virus serotype infection specifies the activation of the unfolded protein response","volume":"4","author":"Umareddy","year":"2007","journal-title":"Virol. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1128\/JVI.02050-10","article-title":"West Nile virus differentially modulates the unfolded protein response to facilitate replication and immune evasion","volume":"85","author":"Ambrose","year":"2011","journal-title":"J. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1128\/JVI.02097-12","article-title":"ATF6 signaling is required for efficient West Nile virus replication by promoting cell survival and inhibition of innate immune responses","volume":"87","author":"Ambrose","year":"2013","journal-title":"J. Virol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Wang, Q., Xin, X., Wang, T., Wan, J., Ou, Y., Yang, Z., Yu, Q., Zhu, L., Guo, Y., and Wu, Y. (2019). Japanese Encephalitis Virus Induces Apoptosis and Encephalitis by Activating the PERK Pathway. J. Virol., 93.","DOI":"10.1128\/JVI.00887-19"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Blazquez, A.B., Martin-Acebes, M.A., and Saiz, J.C. (2014). Amino acid substitutions in the non-structural proteins 4A or 4B modulate the induction of autophagy in West Nile virus infected cells independently of the activation of the unfolded protein response. Front. Microbiol., 5.","DOI":"10.3389\/fmicb.2014.00797"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.virusres.2013.10.012","article-title":"Tick-borne encephalitis virus triggers inositol-requiring enzyme 1 (IRE1) and transcription factor 6 (ATF6) pathways of unfolded protein response","volume":"178","author":"Yu","year":"2013","journal-title":"Virus Res."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Breitkopf, V.J.M., Dobler, G., Claus, P., Naim, H.Y., and Steffen, I. (2021). IRE1-Mediated Unfolded Protein Response Promotes the Replication of Tick-Borne Flaviviruses in a Virus and Cell-Type Dependent Manner. Viruses, 13.","DOI":"10.3390\/v13112164"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Lewy, T.G., Offerdahl, D.K., Grabowski, J.M., Kellman, E., Mlera, L., Chiramel, A., and Bloom, M.E. (2020). PERK-Mediated Unfolded Protein Response Signaling Restricts Replication of the Tick-Borne Flavivirus Langat Virus. Viruses, 12.","DOI":"10.3390\/v12030328"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.1128\/JVI.76.9.4162-4171.2002","article-title":"Japanese encephalitis virus infection initiates endoplasmic reticulum stress and an unfolded protein response","volume":"76","author":"Su","year":"2002","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12985-015-0269-5","article-title":"Constant up-regulation of BiP\/GRP78 expression prevents virus-induced apoptosis in BHK-21 cells with Japanese encephalitis virus persistent infection","volume":"12","author":"Lyoo","year":"2015","journal-title":"Virol. J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.bbrc.2017.02.006","article-title":"The host cell response to tick-borne encephalitis virus","volume":"492","author":"Carletti","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1099\/vir.0.057265-0","article-title":"Regulated IRE1-dependent decay pathway is activated during Japanese encephalitis virus-induced unfolded protein response and benefits viral replication","volume":"95","author":"Bhattacharyya","year":"2014","journal-title":"J. Gen. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"102269","DOI":"10.1016\/j.ttbdis.2023.102269","article-title":"Cellular stress is triggered by tick-borne encephalitis virus and limits the virus replication in PMJ2-R mouse macrophage cell line","volume":"15","author":"Berankova","year":"2024","journal-title":"Ticks Tick Borne Dis."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Wang, S., Yang, K., Li, C., Liu, W., Gao, T., Yuan, F., Guo, R., Liu, Z., Tan, Y., and Hu, X. (2023). 4-Phenyl-butyric Acid Inhibits Japanese Encephalitis Virus Replication via Inhibiting Endoplasmic Reticulum Stress Response. Viruses, 15.","DOI":"10.3390\/v15020534"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Blazquez, A.B., Escribano-Romero, E., Merino-Ramos, T., Saiz, J.C., and Martin-Acebes, M.A. (2013). Infection with Usutu virus induces an autophagic response in mammalian cells. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002509"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"7453","DOI":"10.1128\/JVI.76.15.7453-7459.2002","article-title":"Hepatitis C virus subgenomic replicons induce endoplasmic reticulum stress activating an intracellular signaling pathway","volume":"76","author":"Tardif","year":"2002","journal-title":"J. Virol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"17158","DOI":"10.1074\/jbc.M312144200","article-title":"Hepatitis C virus suppresses the IRE1-XBP1 pathway of the unfolded protein response","volume":"279","author":"Tardif","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1096\/fj.04-3455fje","article-title":"Hepatitis C virus envelope proteins regulate CHOP via induction of the unfolded protein response","volume":"19","author":"Chan","year":"2005","journal-title":"FASEB J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1007\/s00705-009-0495-5","article-title":"Effects of hepatitis C virus envelope glycoprotein unfolded protein response activation on translation and transcription","volume":"154","author":"Chan","year":"2009","journal-title":"Arch. Virol."},{"key":"ref_110","first-page":"529","article-title":"Hepatitis C virus non-structural protein NS4B can modulate an unfolded protein response","volume":"43","author":"Zheng","year":"2005","journal-title":"J. Microbiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/hep.22464","article-title":"Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response","volume":"48","author":"Sir","year":"2008","journal-title":"Hepatology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1172\/JCI41474","article-title":"Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro","volume":"121","author":"Ke","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"766","DOI":"10.4161\/auto.27954","article-title":"Hepatitis C virus core protein activates autophagy through EIF2AK3 and ATF6 UPR pathway-mediated MAP1LC3B and ATG12 expression","volume":"10","author":"Wang","year":"2014","journal-title":"Autophagy"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"10724","DOI":"10.1128\/JVI.01667-12","article-title":"Hepatitis C virus-induced autophagy is independent of the unfolded protein response","volume":"86","author":"Mohl","year":"2012","journal-title":"J. Virol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/j.1478-3231.2010.02210.x","article-title":"Hepatitis C virus protein and iron overload induce hepatic steatosis through the unfolded protein response in mice","volume":"30","author":"Nishina","year":"2010","journal-title":"Liver Int."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/path.2703","article-title":"In vivo hepatic endoplasmic reticulum stress in patients with chronic hepatitis C","volume":"221","author":"Asselah","year":"2010","journal-title":"J. Pathol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1440-1746.2010.06368.x","article-title":"No evidence of the unfolded protein response in patients with chronic hepatitis C virus infection","volume":"26","author":"McPherson","year":"2011","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"33466","DOI":"10.1074\/jbc.M109.019810","article-title":"Hepatitis C virus proteins induce lipogenesis and defective triglyceride secretion in transgenic mice","volume":"284","author":"Lerat","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"da Fonseca, F.G., Serufo, A.V., Leao, T.L., and Lourenco, K.L. (2024). Viral Infections and Their Ability to Modulate Endoplasmic Reticulum Stress Response Pathways. Viruses, 16.","DOI":"10.3390\/v16101555"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3109\/1040841X.2013.813899","article-title":"The expanding roles of endoplasmic reticulum stress in virus replication and pathogenesis","volume":"41","author":"Li","year":"2015","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Turpin, J., El-Safadi, D., Lebeau, G., Frumence, E., Despres, P., Viranaicken, W., and Krejbich-Trotot, P. (2021). CHOP Pro-Apoptotic Transcriptional Program in Response to ER Stress Is Hacked by Zika Virus. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073750"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Ricciardi-Jorge, T., da Rocha, E.L., Gonzalez-Kozlova, E., Rodrigues-Luiz, G.F., Ferguson, B.J., Sweeney, T., Irigoyen, N., and Mansur, D.S. (2023). PKR-mediated stress response enhances dengue and Zika virus replication. mBio, 14.","DOI":"10.1128\/mbio.00934-23"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"103930","DOI":"10.1016\/j.ibmb.2023.103930","article-title":"The chaperone BiP promotes dengue virus replication and mosquito vitellogenesis in Aedes aegypti","volume":"155","author":"Yeh","year":"2023","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/s41419-020-2297-3","article-title":"Lipid droplets: Platforms with multiple functions in cancer hallmarks","volume":"11","author":"Cruz","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.bbalip.2015.12.010","article-title":"Lipid droplets, lipophagy, and beyond","volume":"1861","author":"Wang","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Kumar, A., Yadav, S., and Choudhary, V. (2024). The evolving landscape of ER-LD contact sites. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1483902"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.jmb.2019.12.031","article-title":"RAB18 Loss Interferes with Lipid Droplet Catabolism and Provokes Autophagy Network Adaptations","volume":"432","author":"Bekbulat","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1038\/s41467-018-05278-2","article-title":"Seipin and the membrane-shaping protein Pex30 cooperate in organelle budding from the endoplasmic reticulum","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Neefjes, J., and Cabukusta, B. (2021). What the VAP: The Expanded VAP Family of Proteins Interacting with FFAT and FFAT-Related Motifs for Interorganellar Contact. Contact, 4.","DOI":"10.1177\/25152564211012246"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1083\/jcb.201704184","article-title":"Rab18 promotes lipid droplet (LD) growth by tethering the ER to LDs through SNARE and NRZ interactions","volume":"217","author":"Xu","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cmet.2012.09.003","article-title":"IRE1alpha-XBP1s induces PDI expression to increase MTP activity for hepatic VLDL assembly and lipid homeostasis","volume":"16","author":"Wang","year":"2012","journal-title":"Cell Metab."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1091\/mbc.E16-01-0039","article-title":"Transcription factor ATF4 directs basal and stress-induced gene expression in the unfolded protein response and cholesterol metabolism in the liver","volume":"27","author":"Fusakio","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/j.bbagrm.2016.07.010","article-title":"ATF4 regulates SREBP1c expression to control fatty acids synthesis in 3T3-L1 adipocytes differentiation","volume":"1859","author":"Chen","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12974-023-02736-7","article-title":"Metabolic reprogramming and lipid droplets are involved in Zika virus replication in neural cells","volume":"20","author":"Dias","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1074\/mcp.R116.065649","article-title":"Protein Interactions during the Flavivirus and Hepacivirus Life Cycle","volume":"16","author":"Gerold","year":"2017","journal-title":"Mol. Cell Proteom."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Zhang, J., Lan, Y., and Sanyal, S. (2017). Modulation of Lipid Droplet Metabolism-A Potential Target for Therapeutic Intervention in Flaviviridae Infections. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.02286"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Qin, Z.L., Yao, Q.F., Ren, H., Zhao, P., and Qi, Z.T. (2022). Lipid Droplets and Their Participation in Zika Virus Infection. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012584"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Rothan, H.A., and Kumar, M. (2019). Role of Endoplasmic Reticulum-Associated Proteins in Flavivirus Replication and Assembly Complexes. Pathogens, 8.","DOI":"10.3390\/pathogens8030148"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1080\/1040841X.2023.2224424","article-title":"Interplay between lipid metabolism, lipid droplets and RNA virus replication","volume":"50","author":"Farias","year":"2024","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1002\/1873-3468.14819","article-title":"Lipid Droplets in Virus Replication","volume":"598","author":"Herker","year":"2024","journal-title":"FEBS Lett."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4303","DOI":"10.1038\/s41467-021-24632-5","article-title":"Intracellular lipid droplet accumulation occurs early following viral infection and is required for an efficient interferon response","volume":"12","author":"Monson","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"11513","DOI":"10.1074\/jbc.REV120.012784","article-title":"Viperin: An ancient radical SAM enzyme finds its place in modern cellular metabolism and innate immunity","volume":"295","author":"Ghosh","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Liao, P.C., Yang, E.J., Borgman, T., Boldogh, I.R., Sing, C.N., Swayne, T.C., and Pon, L.A. (2022). Touch and Go: Membrane Contact Sites Between Lipid Droplets and Other Organelles. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.852021"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"105423","DOI":"10.1016\/j.antiviral.2022.105423","article-title":"Flavivirus NS4B protein: Structure, function, and antiviral discovery","volume":"207","author":"Wang","year":"2022","journal-title":"Antivir. Res."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Klaitong, P., and Smith, D.R. (2021). Roles of Non-Structural Protein 4A in Flavivirus Infection. Viruses, 13.","DOI":"10.3390\/v13102077"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"6793","DOI":"10.1128\/JVI.00045-14","article-title":"Rab18 facilitates dengue virus infection by targeting fatty acid synthase to sites of viral replication","volume":"88","author":"Tang","year":"2014","journal-title":"J. Virol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"E869","DOI":"10.1073\/pnas.1115623109","article-title":"The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule","volume":"109","author":"Cross","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2016.03.006","article-title":"Novel dengue virus inhibitor 4-HPR activates ATF4 independent of protein kinase R-like Endoplasmic Reticulum Kinase and elevates levels of eIF2alpha phosphorylation in virus infected cells","volume":"130","author":"Fraser","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Dias, S.S.G., Cunha-Fernandes, T., Soares, V.C., de Almeida, C.J., and Bozza, P.T. (2023). Lipid droplets in Zika neuroinfection: Potential targets for intervention?. Mem. Inst. Oswaldo Cruz, 118.","DOI":"10.1590\/0074-02760230044"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.4049\/jimmunol.1901310","article-title":"AMP-Activated Protein Kinase Restricts Zika Virus Replication in Endothelial Cells by Potentiating Innate Antiviral Responses and Inhibiting Glycolysis","volume":"204","author":"Singh","year":"2020","journal-title":"J. Immunol."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Datey, A., Chatterjee, S., Ghosh, S., Kumar, P.S., De, S., Ghorai, U., Hota, D., Subudhi, B.B., and Chattopadhyay, S. (2025). Telmisartan, an anti-hypertensive drug, impedes JEV infection, possibly via the AT1\/PPARgamma axis. Microbiol. Spectr., 13.","DOI":"10.1128\/spectrum.03003-24"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/s41467-023-36298-2","article-title":"The p97-UBXD8 complex regulates ER-Mitochondria contact sites by altering membrane lipid saturation and composition","volume":"14","author":"Ganji","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"22147","DOI":"10.1074\/jbc.M110.192500","article-title":"Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication","volume":"286","author":"McLean","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"S319","DOI":"10.1093\/infdis\/jiw270","article-title":"FAM134B, the Selective Autophagy Receptor for Endoplasmic Reticulum Turnover, Inhibits Replication of Ebola Virus Strains Makona and Mayinga","volume":"214","author":"Chiramel","year":"2016","journal-title":"J. Infect. 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