{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:12:06Z","timestamp":1790475126743,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"POE FEDER 2014-20 of the Conseil R\u00e9gional de La R\u00e9union","award":["ZIKAlert program, n\u25e6 SYNERGIE RE00001902"],"award-info":[{"award-number":["ZIKAlert program, n\u25e6 SYNERGIE RE00001902"]}]},{"name":"BioST F\u00e9d\u00e9ration of La R\u00e9union University","award":["X926FEDE-26"],"award-info":[{"award-number":["X926FEDE-26"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mosquito-borne Zika virus (ZIKV) became a real threat to human health due to the lack of vaccine and effective antiviral treatment. The virus has recently been responsible for a global outbreak leading to millions of infected cases. ZIKV complications were highlighted in adults with Guillain\u2013Barr\u00e9 syndrome and in newborns with increasing numbers of congenital disorders ranging from mild developmental delays to fatal conditions. The ability of ZIKV to establish a long-term infection in diverse organs including the kidneys has been recently documented but the consequences of such a viral infection are still debated. Our study aimed to determine whether the efficiency of ZIKV growth in kidney cells relates to glucose concentration. Human kidney HK-2 cells were infected with different ZIKV strains in presence of normal and high glucose concentrations. Virological assays showed a decrease in viral replication without modifying entry steps (viral binding, internalization, fusion) under high glucose conditions. This decrease replication was associated with a lower virus progeny and increased cell viability when compared to ZIKV-infected HK-2 cells in normal glucose concentration. In conclusion, we showed for the first time that an elevated glucose level influences ZIKV replication level with an effect on kidney cell survival.<\/jats:p>","DOI":"10.3390\/ijms22052495","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T10:36:37Z","timestamp":1614681397000},"page":"2495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Zika Virus Growth in Human Kidney Cells Is Restricted by an Elevated Glucose Level"],"prefix":"10.3390","volume":"22","author":[{"given":"Alawiya","family":"Reslan","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, Universit\u00e9 de la R\u00e9union, INSERM U1187, CNRS UMR 9192, IRD UMR 249, 94791 Sainte Clotilde, La R\u00e9union, France"},{"name":"Unit\u00e9 Mixte Diab\u00e8te ath\u00e9rothrombose Th\u00e9rapies R\u00e9union Oc\u00e9an Indien, Plateforme Technologique CYROI, Universit\u00e9 de la R\u00e9union, INSERM U1188, 94791 Sainte Clotilde, La R\u00e9union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5035-0162","authenticated-orcid":false,"given":"Juliano G.","family":"Haddad","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, Universit\u00e9 de la R\u00e9union, INSERM U1187, CNRS UMR 9192, IRD UMR 249, 94791 Sainte Clotilde, La R\u00e9union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liadrine","family":"Moukendza Koundi","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, Universit\u00e9 de la R\u00e9union, INSERM U1187, CNRS UMR 9192, IRD UMR 249, 94791 Sainte Clotilde, La R\u00e9union, France"},{"name":"Unit\u00e9 Mixte Diab\u00e8te ath\u00e9rothrombose Th\u00e9rapies R\u00e9union Oc\u00e9an Indien, Plateforme Technologique CYROI, Universit\u00e9 de la R\u00e9union, INSERM U1188, 94791 Sainte Clotilde, La R\u00e9union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8926-4050","authenticated-orcid":false,"given":"Philippe","family":"Despr\u00e8s","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, Universit\u00e9 de la R\u00e9union, INSERM U1187, CNRS UMR 9192, IRD UMR 249, 94791 Sainte Clotilde, La R\u00e9union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1667-5913","authenticated-orcid":false,"given":"Jean-Loup","family":"Bascands","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte Diab\u00e8te ath\u00e9rothrombose Th\u00e9rapies R\u00e9union Oc\u00e9an Indien, Plateforme Technologique CYROI, Universit\u00e9 de la R\u00e9union, INSERM U1188, 94791 Sainte Clotilde, La R\u00e9union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6325-4866","authenticated-orcid":false,"given":"Gilles","family":"Gadea","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, Universit\u00e9 de la R\u00e9union, INSERM U1187, CNRS UMR 9192, IRD UMR 249, 94791 Sainte Clotilde, La R\u00e9union, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1056\/NEJMoa0805715","article-title":"Zika Virus Outbreak on Yap Island, Federated States of Micronesia","volume":"360","author":"Duffy","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1099\/jgv.0.000381","article-title":"Zika Virus: A Previously Slow Pandemic Spreads Rapidly through the Americas","volume":"97","author":"Gatherer","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/S0140-6736(16)00562-6","article-title":"Guillain-Barr\u00e9 Syndrome Outbreak Associated with Zika Virus Infection in French Polynesia: A Case-Control Study","volume":"387","author":"Blake","year":"2016","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Merfeld, E., Ben-Avi, L., Kennon, M., and Cerveny, K.L. (2017). Potential Mechanisms of Zika-Linked Microcephaly: Zika-Linked Microcephaly. Wiley Interdiscip. Rev. Dev. Biol., 6.","DOI":"10.1002\/wdev.273"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1056\/NEJMoa1605564","article-title":"Guillain\u2013Barr\u00e9 Syndrome Associated with Zika Virus Infection in Colombia","volume":"375","author":"Parra","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1056\/NEJMc1604449","article-title":"Evidence of Sexual Transmission of Zika Virus","volume":"374","author":"Matheron","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1016\/S0140-6736(16)30428-7","article-title":"Zika Virus: A New Challenge for Blood Transfusion","volume":"387","author":"Musso","year":"2016","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1056\/NEJMc1607262","article-title":"Evidence for Transmission of Zika Virus by Platelet Transfusion","volume":"375","author":"Motta","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3390\/v3020160","article-title":"Flavivirus Cell Entry and Membrane Fusion","volume":"3","author":"Smit","year":"2011","journal-title":"Viruses"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s00726-009-0370-4","article-title":"Molecular Mechanisms of Flavivirus Membrane Fusion","volume":"41","author":"Stiasny","year":"2011","journal-title":"Amino Acids"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1086\/648731","article-title":"Persistent Infection with West Nile Virus Years after Initial Infection","volume":"201","author":"Murray","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1053\/j.ackd.2019.01.002","article-title":"Flaviviruses and Kidney Diseases","volume":"26","author":"Burdmann","year":"2019","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s00109-018-1692-z","article-title":"Zika Virus Infection and Implications for Kidney Disease","volume":"96","author":"Alcendor","year":"2018","journal-title":"J. Mol. Med."},{"key":"ref_14","unstructured":"(2021, January 06). Available online: Www.Who.Int\/News-Room\/Fact-Sheets\/Details\/Diabetes."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S0140-6736(13)60439-0","article-title":"Evolving Importance of Kidney Disease: From Subspecialty to Global Health Burden","volume":"382","author":"Eckardt","year":"2013","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"A7","DOI":"10.1053\/j.ajkd.2013.11.001","article-title":"US Renal Data System 2013 Annual Data Report","volume":"63","author":"Collins","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1681\/ASN.2012070718","article-title":"Kidney Disease and Increased Mortality Risk in Type 2 Diabetes","volume":"24","author":"Afkarian","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1093\/infdis\/jix171","article-title":"Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis","volume":"216","author":"Alcendor","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"F401","DOI":"10.1152\/ajprenal.00408.2004","article-title":"High Ambient Glucose Is Effect Neutral on Cell Death and Proliferation in Human Proximal Tubular Epithelial Cells","volume":"289","author":"Morais","year":"2005","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.virol.2016.07.015","article-title":"A Robust Method for the Rapid Generation of Recombinant Zika Virus Expressing the GFP Reporter Gene","volume":"497","author":"Gadea","year":"2016","journal-title":"Virology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.virol.2017.12.003","article-title":"The Structural Proteins of Epidemic and Historical Strains of Zika Virus Differ in Their Ability to Initiate Viral Infection in Human Host Cells","volume":"516","author":"Bos","year":"2018","journal-title":"Virology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bos, S., Viranaicken, W., Frumence, E., Li, G., Despr\u00e8s, P., Zhao, R.Y., and Gadea, G. (2019). The Envelope Residues E152\/156\/158 of Zika Virus Influence the Early Stages of Virus Infection in Human Cells. Cells, 8.","DOI":"10.3390\/cells8111444"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.micinf.2010.09.005","article-title":"Molecular Mechanisms Involved in the Early Steps of Flavivirus Cell Entry","volume":"13","author":"Kaufmann","year":"2011","journal-title":"Microbes Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.ijbiomac.2017.06.105","article-title":"Epigallocatechin Gallate, an Active Green Tea Compound Inhibits the Zika Virus Entry into Host Cells via Binding the Envelope Protein","volume":"104","author":"Sharma","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gaudry, A., Bos, S., Viranaicken, W., Roche, M., Krejbich-Trotot, P., Gadea, G., Despr\u00e8s, P., and El-Kalamouni, C. (2018). The Flavonoid Isoquercitrin Precludes Initiation of Zika Virus Infection in Human Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041093"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Roth, H., Magg, V., Uch, F., Mutz, P., Klein, P., Haneke, K., Lohmann, V., Bartenschlager, R., Fackler, O.T., and Locker, N. (2017). Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses. mBio, 8.","DOI":"10.1128\/mBio.02150-16"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"F219","DOI":"10.1152\/ajprenal.00207.2010","article-title":"Ribosomal Biogenesis Induction by High Glucose Requires Activation of Upstream Binding Factor in Kidney Glomerular Epithelial Cells","volume":"300","author":"Mariappan","year":"2011","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.micinf.2010.04.005","article-title":"West Nile Virus Capsid Protein Interaction with Importin and HDM2 Protein Is Regulated by Protein Kinase C-Mediated Phosphorylation","volume":"12","author":"Bhuvanakantham","year":"2010","journal-title":"Microbes Infect."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.virol.2006.01.022","article-title":"Analysis of the Endocytic Pathway Mediating the Infectious Entry of Mosquito-Borne Flavivirus West Nile into Aedes Albopictus Mosquito (C6\/36) Cells","volume":"349","author":"Chu","year":"2006","journal-title":"Virology"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"(2018). Ana Bl\u00e1zquez; \u00c1ngela V\u00e1zquez-Calvo; Miguel Mart\u00edn-Acebes; Juan-Carlos Saiz Pharmacological Inhibition of Protein Kinase C Reduces West Nile Virus Replication. Viruses, 10.","DOI":"10.3390\/v10020091"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12985-016-0494-6","article-title":"Inhibition of Protein Kinase C Promotes Dengue Virus Replication","volume":"13","author":"Noppakunmongkolchai","year":"2016","journal-title":"Virol. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"667","DOI":"10.2337\/diab.39.6.667","article-title":"Increase in Diacylglycerol Mass in Isolated Glomeruli by Glucose From De Novo Synthesis of Glycerolipids","volume":"39","author":"Craven","year":"1990","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"F571","DOI":"10.1152\/ajprenal.1991.261.4.F571","article-title":"High Glucose Increases Diacylglycerol Mass and Activates Protein Kinase C in Mesangial Cell Cultures","volume":"261","author":"Ayo","year":"1991","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/ki.1993.213","article-title":"Activation of Protein Kinase C Reduces Thromboxane Receptors in Glomeruli and Mesangial Cells","volume":"44","author":"Studer","year":"1993","journal-title":"Kidney Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1681\/ASN.2007121313","article-title":"Proteinuria and Hyperglycemia Induce Endoplasmic Reticulum Stress","volume":"19","author":"Lindenmeyer","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1016\/j.celrep.2017.02.014","article-title":"Ultrastructural Characterization of Zika Virus Replication Factories","volume":"18","author":"Cortese","year":"2017","journal-title":"Cell Rep."},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ejphar.2018.10.026","article-title":"Nrf2, a Novel Molecular Target to Reduce Type 1 Diabetes Associated Secondary Complications: The Basic Considerations","volume":"843","author":"Negi","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yoh, K., Hirayama, A., Ishizaki, K., Yamada, A., Takeuchi, M., Yamagishi, S., Morito, N., Nakano, T., Ojima, M., and Shimohata, H. (2008). Hyperglycemia Induces Oxidative and Nitrosative Stress and Increases Renal Functional Impairment in Nrf2-Deficient Mice. Genes Cells.","DOI":"10.1111\/j.1365-2443.2008.01234.x"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"850","DOI":"10.2337\/db09-1342","article-title":"The Protective Role of Nrf2 in Streptozotocin-Induced Diabetic Nephropathy","volume":"59","author":"Jiang","year":"2010","journal-title":"Diabetes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.3892\/etm.2016.3033","article-title":"Grape Seed Proanthocyanidin Extract Protects the Retina against Early Diabetic Injury by Activating the Nrf2 Pathway","volume":"11","author":"Sun","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4938","DOI":"10.1038\/s41467-020-18764-3","article-title":"SARS-CoV2-Mediated Suppression of NRF2-Signaling Reveals Potent Antiviral and Anti-Inflammatory Activity of 4-Octyl-Itaconate and Dimethyl Fumarate","volume":"11","author":"Olagnier","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1093\/infdis\/jis221","article-title":"Evaluation for West Nile Virus (WNV) RNA in Urine of Patients Within 5 Months of WNV Infection","volume":"205","author":"Baty","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jviromet.2016.07.014","article-title":"Detection of Zika Virus by SYBR Green One-Step Real-Time RT-PCR","volume":"236","author":"Xu","year":"2016","journal-title":"J. Virol. 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