{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:41:11Z","timestamp":1792298471352,"version":"4.4.0"},"reference-count":79,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T00:00:00Z","timestamp":1592352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013674","name":"College of Veterinary Medicine and Biomedical Sciences","doi-asserted-by":"publisher","award":["College Research Council"],"award-info":[{"award-number":["College Research Council"]}],"id":[{"id":"10.13039\/100013674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013674","name":"College of Veterinary Medicine and Biomedical Sciences","doi-asserted-by":"publisher","award":["Department of Microbiology, Immunology and Pathology"],"award-info":[{"award-number":["Department of Microbiology, Immunology and Pathology"]}],"id":[{"id":"10.13039\/100013674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Dengue virus infection is associated with the upregulation of metabolic pathways within infected cells. This effect is common to infection by a broad array of viruses. These metabolic changes, including increased glucose metabolism, oxidative phosphorylation and autophagy, support the demands of viral genome replication and infectious particle formation. The mechanisms by which these changes occur are known to be, in part, directed by viral nonstructural proteins that contact and control cellular structures and metabolic enzymes. We investigated the roles of host proteins with overarching control of metabolic processes, the transcriptional regulators, cyclin-dependent kinase 8 (CDK8) and its paralog, CDK19, as mediators of virally induced metabolic changes. Here, we show that expression of CDK8, but not CDK19, is increased during dengue virus infection in Huh7 human hepatocellular carcinoma cells, although both are required for efficient viral replication. Chemical inhibition of CDK8 and CDK19 with Senexin A during infection blocks virus-induced expression of select metabolic and autophagic genes, hexokinase 2 (HK2) and microtubule-associated protein 1 light chain 3 (LC3), and reduces viral genome replication and infectious particle production. The results further define the dependence of virus replication on increased metabolic capacity in target cells and identify CDK8 and CDK19 as master regulators of key metabolic genes. The common inhibition of CDK8 and CDK19 offers a host-directed therapeutic intervention that is unlikely to be overcome by viral evolution.<\/jats:p>","DOI":"10.3390\/v12060654","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T13:11:32Z","timestamp":1592399492000},"page":"654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cyclin-Dependent Kinases 8 and 19 Regulate Host Cell Metabolism during Dengue Virus Serotype 2 Infection"],"prefix":"10.3390","volume":"12","author":[{"given":"Molly","family":"Butler","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nunya","family":"Chotiwan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"},{"name":"Arthropod-borne Infectious Disease Laboratories, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie D.","family":"Brewster","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"DiLisio","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Ackart","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan K.","family":"Podell","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall J.","family":"Basaraba","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6798-2537","authenticated-orcid":false,"given":"Rushika","family":"Perera","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"},{"name":"Arthropod-borne Infectious Disease Laboratories, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra L.","family":"Quackenbush","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4518-9030","authenticated-orcid":false,"given":"Joel","family":"Rovnak","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,17]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2020, January 20). Dengue and Severe Dengue. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dengue-and-severe-dengue."},{"key":"ref_2","unstructured":"World Health Organization, and Pan American Health Organization (2019, November 13). Epidemiological Update: Dengue. Available online: http:\/\/www.paho.org."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.3389\/fimmu.2019.01533","article-title":"Hijacking the supplies: Metabolism as a novel facet of virus-host interaction","volume":"10","author":"Mayer","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fcimb.2019.00095","article-title":"Virus control of cell metabolism for replication and evasion of host immune responses","volume":"9","author":"Kolstoe","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Thaker, S.K., Ch\u2019ng, J., and Christofk, H.R. (2019). Viral hijacking of cellular metabolism. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0678-9"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chotiwan, N., Andre, B.G., Sanchez-Vargas, I., Islam, M.N., Grabowski, J.M., Hopf-Jannasch, A., Gough, E., Nakayasu, E., Blair, C.D., and Belisle, J.T. (2018). Dynamic remodeling of lipids coincides with dengue virus replication in the midgut of Aedes aegypti mosquitoes. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006853"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00458-17","DOI":"10.1128\/mSphere.00458-17","article-title":"Anaplerotic role of glucose in the oxidation of endogenous fatty acids during dengue virus infection","volume":"3","author":"Zeidler","year":"2018","journal-title":"mSphere"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1128\/JVI.02309-14","article-title":"Dengue virus induces and requires glycolysis for optimal replication","volume":"89","author":"Fontaine","year":"2015","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gullberg, R.C., Steel, J.J., Pujari, V., Rovnak, J., Crick, D.C., and Perera, R. (2018). Stearoly-CoA desaturase 1 differentiates early and advanced dengue virus infections and determines virus particle infectivity. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007261"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17345","DOI":"10.1073\/pnas.1010811107","article-title":"Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis","volume":"107","author":"Heaton","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.chom.2010.10.006","article-title":"Dengue virus-induced autophagy regulates lipid metabolism","volume":"8","author":"Heaton","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11826","DOI":"10.1038\/s41598-018-30385-x","article-title":"The role of lipids in the inception, maintenance and complications of dengue virus infection","volume":"8","author":"Melo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Perera, R., Riley, C., Isaac, G., Hopf-Jannasch, A.S., Moore, R.J., Weitz, K.W., Pasa-Tolic, L., Metz, T.O., Adamec, J., and Kuhn, R.J. (2012). Dengue virus infection perturbs lipid homeostasis in infected mosquito cells. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002584"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"362","DOI":"10.3389\/fcimb.2018.00362","article-title":"Autophagy, EVs, and Infections: A perfect question for a perfect time","volume":"8","author":"Pleet","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e79","DOI":"10.1016\/S1473-3099(16)30471-6","article-title":"Prevention and control of dengue-the light at the end of the tunnel","volume":"17","author":"Pang","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0140-6736(14)60572-9","article-title":"Dengue","volume":"385","author":"Guzman","year":"2015","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/S0140-6736(07)61687-0","article-title":"Dengue","volume":"370","author":"Halstead","year":"2007","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1038\/s41598-019-39157-7","article-title":"Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity","volume":"9","author":"Silva","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Abernathy, E., Mateo, R., Majzoub, K., van Buuren, N., Bird, S.W., Carette, J.E., and Kirkegaard, K. (2019). Differential and convergent utilization of autophagy components by positive-strand RNA viruses. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.2006926"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chen, H.R., Chuang, Y.C., Lin, Y.S., Liu, H.S., Liu, C.C., Perng, G.C., and Yeh, T.M. (2016). Dengue virus nonstructural protein 1 induces vascular leakage through macrophage migration inhibitory factor and autophagy. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004828"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e02020-16","DOI":"10.1128\/JVI.02020-16","article-title":"Dengue virus activates the AMP kinase-mTOR axis to stimulate a proviral lipophagy","volume":"91","author":"Jordan","year":"2017","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.virol.2008.02.016","article-title":"Autophagic machinery activated by dengue virus enhances virus replication","volume":"374","author":"Lee","year":"2008","journal-title":"Virology"},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"11871","DOI":"10.1128\/JVI.01342-15","article-title":"Dengue virus NS1 protein modulates cellular energy metabolism by increasing glyceraldehyde-3-phosphate dehydrogenase activity","volume":"89","author":"Allonso","year":"2015","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.immuni.2012.10.017","article-title":"CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response","volume":"38","author":"Bancerek","year":"2013","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nsmb.1752","article-title":"CDK8 is a positive regulator of transcriptional elongation within the serum response network","volume":"17","author":"Donner","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.cell.2013.04.048","article-title":"HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia","volume":"153","author":"Galbraith","year":"2013","journal-title":"Cell"},{"key":"ref_29","first-page":"1447","article-title":"Cooperative activity of cdk8 and GCN5L within Mediator directs tandem phosphoacetylation of histone H3","volume":"27","author":"Meyer","year":"2008","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1172\/JCI61462","article-title":"Regulation of lipogenesis by cyclin-dependent kinase 8-mediated control of SREBP-1","volume":"122","author":"Zhao","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5450","DOI":"10.1128\/JVI.00464-15","article-title":"Retroviral cyclin controls cyclin-dependent kinase 8-mediated transcription elongation and reinitiation","volume":"89","author":"Birkenheuer","year":"2015","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.1128\/JVI.07006-11","article-title":"Retroviral cyclin enhances cyclin-dependent kinase 8 activity","volume":"86","author":"Rovnak","year":"2012","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.celrep.2017.10.058","article-title":"CDK8 kinase activity promotes glycolysis","volume":"21","author":"Galbraith","year":"2017","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.cmet.2018.02.023","article-title":"The TORC1-regulated CPA complex rewires an RNA processing network to drive autophagy and metabolic reprogramming","volume":"27","author":"Tang","year":"2018","journal-title":"Cell Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.virol.2010.10.022","article-title":"The retroviral cyclin of walleye dermal sarcoma virus binds cyclin-dependent kinases 3 and 8","volume":"409","author":"Brewster","year":"2011","journal-title":"Virology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8031","DOI":"10.1128\/JVI.76.16.8031-8039.2002","article-title":"Walleye dermal sarcoma virus cyclin interacts with components of the Mediator complex and the RNA polymerase II holoenzyme","volume":"76","author":"Rovnak","year":"2002","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12558","DOI":"10.18632\/oncotarget.14894","article-title":"Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer","volume":"8","author":"McDermott","year":"2017","journal-title":"Oncotarget"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13799","DOI":"10.1073\/pnas.1206906109","article-title":"Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities","volume":"109","author":"Porter","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1006\/viro.1997.8500","article-title":"Construction of infectious cDNA clones for dengue 2 virus: Strain 16681 and its attenuated vaccine derivative, strain PDK-53","volume":"230","author":"Kinney","year":"1997","journal-title":"Virology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/1743-422X-4-130","article-title":"Determination of suitable housekeeping genes for normalisation of quantitative real time PCR analysis of cells infected with human immunodeficiency virus and herpes viruses","volume":"4","author":"Watson","year":"2007","journal-title":"Virol. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1128\/JCM.37.8.2543-2547.1999","article-title":"Detection of dengue virus RNA in patients after primary or secondary dengue infection by using the TaqMan automated amplification system","volume":"37","author":"Laue","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1084\/jem.20101470","article-title":"Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme","volume":"208","author":"Wolf","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1080\/15548627.2015.1061849","article-title":"Thyroid hormone induction of mitochondrial activity is coupled to mitophagy via ROS-AMPK-ULK1 signaling","volume":"11","author":"Sinha","year":"2015","journal-title":"Autophagy"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/s41467-017-00906-9","article-title":"Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis","volume":"8","author":"Lee","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Haas, R., Smith, J., Rocher-Ros, V., Nadkarni, S., Montero-Melendez, T., D\u2019Acquisto, F., Bland, E.J., Bombardieri, M., Pitzalis, C., and Perretti, M. (2015). Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions. PLoS Biol., 13.","DOI":"10.1371\/journal.pbio.1002202"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"pdb top074542","DOI":"10.1101\/pdb.top074542","article-title":"Isolation of mitochondria from cells and tissues","volume":"2014","author":"Clayton","year":"2014","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1080\/21541264.2018.1556915","article-title":"Regulatory functions of the Mediator kinases CDK8 and CDK19","volume":"10","author":"Fant","year":"2019","journal-title":"Transcription"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.molcel.2019.07.034","article-title":"Transcriptional responses to IFN-gamma require mediator kinase-dependent pause release and mechanistically distinct CDK8 and CDK19 functions","volume":"76","author":"Steinparzer","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4161\/trns.1.1.12373","article-title":"CDK8: A positive regulator of transcription","volume":"1","author":"Galbraith","year":"2010","journal-title":"Transcription"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"De Maio, F.A., Risso, G., Iglesias, N.G., Shah, P., Pozzi, B., Gebhard, L.G., Mammi, P., Mancini, E., Yanovsky, M.J., and Andino, R. (2016). The dengue virus NS5 protein intrudes in the cellular spliceosome and modulates splicing. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005841"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"22621","DOI":"10.1074\/jbc.M113.481382","article-title":"Serotype-specific differences in dengue virus non-structural protein 5 nuclear localization","volume":"288","author":"Hannemann","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.1128\/JVI.03083-12","article-title":"Nuclear localization of dengue virus nonstructural protein 5 does not strictly correlate with efficient viral RNA replication and inhibition of type I interferon signaling","volume":"87","author":"Kumar","year":"2013","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.antiviral.2013.06.002","article-title":"Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin","volume":"99","author":"Tay","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e00626-16","DOI":"10.1128\/MCB.00626-16","article-title":"A kinase-independent role for cyclin-dependent kinase 19 in p53 response","volume":"37","author":"Audetat","year":"2017","journal-title":"Mol. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature07179","article-title":"CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity","volume":"455","author":"Firestein","year":"2008","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.2967\/jnumed.108.060780","article-title":"Evaluation of the role of hexokinase type II in cellular proliferation and apoptosis using human hepatocellular carcinoma cell lines","volume":"50","author":"Ahn","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"John, S., Weiss, J.N., and Ribalet, B. (2011). Subcellular localization of hexokinases I and II directs the metabolic fate of glucose. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017674"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/cdd.2014.173","article-title":"Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy","volume":"22","author":"Roberts","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.virol.2016.10.022","article-title":"Dengue virus induces mitochondrial elongation through impairment of Drp1-triggered mitochondrial fission","volume":"500","author":"Barbier","year":"2017","journal-title":"Virology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nature07976","article-title":"Autophagy regulates lipid metabolism","volume":"458","author":"Singh","year":"2009","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1146\/annurev-nutr-071813-105336","article-title":"Autophagy and lipid droplets in the liver","volume":"35","author":"Singh","year":"2015","journal-title":"Annu. Rev. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e01766-17","DOI":"10.1128\/JVI.01766-17","article-title":"Dengue virus selectively annexes endoplasmic reticulum-associated translation machinery as a strategy for co-opting host cell protein synthesis","volume":"92","author":"Reid","year":"2018","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.virol.2009.03.025","article-title":"Cholesterol biosynthesis modulation regulates dengue viral replication","volume":"389","author":"Rothwell","year":"2009","journal-title":"Virology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.3389\/fmicb.2018.01951","article-title":"Methods for lipid droplet biophysical characterization in flaviviridae infections","volume":"9","author":"Martins","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/ncb1631","article-title":"The lipid droplet is an important organelle for hepatitis C virus production","volume":"9","author":"Miyanari","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.tim.2018.05.010","article-title":"Lipid droplet metabolism during dengue virus infection","volume":"26","author":"Randall","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Samsa, M.M., Mondotte, J.A., Iglesias, N.G., Assuncao-Miranda, I., Barbosa-Lima, G., Da Poian, A.T., Bozza, P.T., and Gamarnik, A.V. (2009). Dengue virus capsid protein usurps lipid droplets for viral particle formation. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000632"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e2127","DOI":"10.1038\/cddis.2015.409","article-title":"Dengue-induced autophagy, virus replication and protection from cell death require ER stress (PERK) pathway activation","volume":"7","author":"Datan","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_69","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":"Blazquez","year":"2015","journal-title":"Autophagy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1128\/JVI.02177-12","article-title":"Inhibition of cellular autophagy deranges dengue virion maturation","volume":"87","author":"Mateo","year":"2013","journal-title":"J. Virol."},{"key":"ref_71","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_72","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.4161\/auto.29455","article-title":"Japanese encephalitis virus replication is negatively regulated by autophagy and occurs on LC3-I- and EDEM1-containing membranes","volume":"10","author":"Sharma","year":"2014","journal-title":"Autophagy"},{"key":"ref_73","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_74","doi-asserted-by":"crossref","first-page":"e47425","DOI":"10.15252\/embr.201847425","article-title":"Mitochondrial translocation of cyclin C stimulates intrinsic apoptosis through Bax recruitment","volume":"20","author":"Jezek","year":"2019","journal-title":"EMBO Rep."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Jezek, J., Smethurst, D.G.J., Stieg, D.C., Kiss, Z.A.C., Hanley, S.E., Ganesan, V., Chang, K.T., Cooper, K.F., and Strich, R. (2019). Cyclin C: The story of a non-cycling cyclin. Biology, 8.","DOI":"10.3390\/biology8010003"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1091\/mbc.E17-08-0493","article-title":"A complex molecular switch directs stress-induced cyclin C nuclear release through SCF(Grr1)-mediated degradation of Med13","volume":"29","author":"Stieg","year":"2018","journal-title":"Mol. Biol. Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.bbadis.2007.08.003","article-title":"Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus","volume":"1772","author":"Midlej","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/infdis\/jiz618","article-title":"Antibody-dependent enhancement of severe disease is mediated by serum viral load in pediatric dengue virus infections","volume":"221","author":"Waggoner","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9072","DOI":"10.1073\/pnas.1303395110","article-title":"Host and viral features of human dengue cases shape the population of infected and infectious Aedes aegypti mosquitoes","volume":"110","author":"Nguyen","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/6\/654\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:40:00Z","timestamp":1760175600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/6\/654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,17]]},"references-count":79,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["v12060654"],"URL":"https:\/\/doi.org\/10.3390\/v12060654","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,17]]}}}