{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T03:35:35Z","timestamp":1770521735160,"version":"3.49.0"},"reference-count":110,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000015","name":"U.S. Department of Energy","doi-asserted-by":"crossref","award":["LDRD 23-ERD-012"],"award-info":[{"award-number":["LDRD 23-ERD-012"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Micronutrient status is recognized to influence host susceptibility to viral infections, yet its impact on Zika virus (ZIKV) pathogenesis remains incompletely understood. We investigated the effects of dietary selenium and combined selenium plus vitamin E deficiency on ZIKV infection outcomes in a type I interferon \u03b1\/\u03b2 receptor knockout (Ifnar1\u2212\/\u2212) murine model. Mice maintained on deficient diets exhibited significantly lower neutralizing antibody titers and reduced levels of key antiviral cytokines (IFN-\u03b3, TNF-\u03b1, IFN-\u03b1, IFN-\u03b2, IL-12p70, CCL5) compared to controls. Correspondingly, higher viral RNA loads were detected in the brains of double-deficient mice, which also experienced greater weight loss and increased mortality. Deep sequencing revealed no major differences in overall viral genome diversity across diet groups; however, specific mutations, including V330L and D67E in the E gene, and V360I in the NS3 gene, were enriched or detected in nutritionally deficient animals. These findings suggest that antioxidant micronutrient deficiency impairs both humoral and cellular immune responses to ZIKV, potentially facilitating enhanced neuroinvasion. While the functional consequences of the identified mutations warrant further investigation, our results underscore the importance of adequate micronutrient intake for optimal antiviral defense. Further studies are needed to clarify the epidemiological significance of these observations.<\/jats:p>","DOI":"10.3390\/v18020177","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:04:46Z","timestamp":1769612686000},"page":"177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Selenium and Vitamin E Deficiency on Zika Virus Pathogenesis and Immune Response in Mice"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0647-498X","authenticated-orcid":false,"given":"Olukunle O.","family":"Oluwasemowo","sequence":"first","affiliation":[{"name":"Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94550, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica E.","family":"Graham","sequence":"additional","affiliation":[{"name":"Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94550, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James B.","family":"Thissen","sequence":"additional","affiliation":[{"name":"Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94550, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aram","family":"Avila-Herrera","sequence":"additional","affiliation":[{"name":"Global Security Computing Applications Division, Computing Directorate, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94550, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-9392","authenticated-orcid":false,"given":"Jeffrey A.","family":"Kimbrel","sequence":"additional","affiliation":[{"name":"Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94550, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepa K.","family":"Murugesh","sequence":"additional","affiliation":[{"name":"Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94550, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-4702","authenticated-orcid":false,"given":"Dina R.","family":"Weilhammer","sequence":"additional","affiliation":[{"name":"Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94550, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6390-9543","authenticated-orcid":false,"given":"Tanya","family":"Tanner","sequence":"additional","affiliation":[{"name":"Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94550, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9068-8712","authenticated-orcid":false,"given":"Nicole M.","family":"Collette","sequence":"additional","affiliation":[{"name":"Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94550, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2924-2313","authenticated-orcid":false,"given":"Monica K.","family":"Borucki","sequence":"additional","affiliation":[{"name":"Biosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, P.O. 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China Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1126\/science.179.4073.588","article-title":"Selenium: Biochemical role as a component of glutathione peroxidase","volume":"179","author":"Rotruck","year":"1973","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1463S","DOI":"10.1093\/jn\/133.5.1463S","article-title":"Selenium deficiency and viral infection","volume":"133","author":"Beck","year":"2003","journal-title":"J. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1089\/ars.2013.5246","article-title":"Toward Understanding Success and Failures in the Use of Selenium for Cancer Prevention","volume":"19","author":"Steinbrenner","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1093\/jn\/137.5.1338","article-title":"Selenium and vitamin E status: Impact on viral pathogenicity","volume":"137","author":"Beck","year":"2007","journal-title":"J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"966S","DOI":"10.1093\/jn\/127.5.966S","article-title":"Increased virulence of coxsackievirus B3 in mice due to vitamin E or selenium deficiency","volume":"127","author":"Beck","year":"1997","journal-title":"J. Nutr."},{"key":"ref_9","first-page":"211","article-title":"Role of Micronutrients in the Response to SARS-CoV-2 Infection in Pediatric Patients","volume":"4","author":"Crespo","year":"2024","journal-title":"Immuno"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Martinez, S.S., Huang, Y., Acuna, L., Laverde, E., Trujillo, D., Barbieri, M.A., Tamargo, J., Campa, A., and Baum, M.K. (2021). Role of Selenium in Viral Infections with a Major Focus on SARS-CoV-2. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010280"},{"key":"ref_11","first-page":"87","article-title":"Effect of Selenium and\/or Vitamin E on Bovine Herpes Type 1 Infection In Vitro Cultured Cells","volume":"61","author":"Mansour","year":"2015","journal-title":"AVMJ"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.34297\/AJBSR.2024.24.003176","article-title":"Critical Analysis of Selenium Deficiency Diseases: An Overview","volume":"24","author":"Gowder","year":"2024","journal-title":"Am. J. Biomed. Sci. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhang, H.Y., Zhang, A.R., Lu, Q.B., Zhang, X.A., Zhang, Z.J., Guan, X.G., Che, T.L., Yang, Y., Li, H., and Liu, W. (2021). Association between fatality rate of COVID-19 and selenium deficiency in China. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06167-8"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3390\/v7010333","article-title":"The association between hantavirus infection and selenium deficiency in mainland China","volume":"7","author":"Fang","year":"2015","journal-title":"Viruses"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"259S","DOI":"10.1093\/ajcn\/57.2.259S","article-title":"The epidemiology of selenium deficiency in the etiological study of endemic diseases in China","volume":"57","author":"Ge","year":"1993","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"144103","DOI":"10.1016\/j.scitotenv.2020.144103","article-title":"Status and risks of selenium deficiency in a traditional selenium-deficient area in Northeast China","volume":"762","author":"Yang","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/S0140-6736(11)61452-9","article-title":"Selenium and human health","volume":"379","author":"Rayman","year":"2012","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1017\/S0007114507832971","article-title":"Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses","volume":"98","author":"Maggini","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1536\/ihj.23-628","article-title":"Recent Advances on Selenium Nutrition and Keshan Disease","volume":"65","author":"Li","year":"2024","journal-title":"Int. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1126\/science.1083516","article-title":"Characterization of mammalian selenoproteomes","volume":"300","author":"Kryukov","year":"2003","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1152\/physrev.00039.2013","article-title":"Selenoproteins: Molecular pathways and physiological roles","volume":"94","author":"Labunskyy","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1089\/ars.2007.1528","article-title":"From selenium to selenoproteins: Synthesis, identity, and their role in human health","volume":"9","author":"Papp","year":"2007","journal-title":"Antioxid. Redox Signal"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.freeradbiomed.2007.03.024","article-title":"Vitamin E, antioxidant and nothing more","volume":"43","author":"Traber","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1093\/jn\/129.11.1951","article-title":"High levels of dietary vitamin E do not replace cellular glutathione peroxidase in protecting mice from acute oxidative stress","volume":"129","author":"Cheng","year":"1999","journal-title":"J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"948S","DOI":"10.1093\/jn\/127.5.948S","article-title":"Nutrition and newly emerging viral diseases: An overview","volume":"127","author":"Levander","year":"1997","journal-title":"J. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1161\/CIRCRESAHA.113.279984","article-title":"Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice","volume":"113","author":"Wortmann","year":"2013","journal-title":"Circ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1073\/pnas.1611576114","article-title":"Selenium deficiency risk predicted to increase under future climate change","volume":"114","author":"Jones","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.3390\/nu7064199","article-title":"Selenium cycling across soil-plant-atmosphere interfaces: A critical review","volume":"7","author":"Winkel","year":"2015","journal-title":"Nutrients"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1086\/315918","article-title":"Host nutritional status and its effect on a viral pathogen","volume":"182","author":"Beck","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1126\/science.7041255","article-title":"Rapid evolution of RNA genomes","volume":"215","author":"Holland","year":"1982","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1128\/MMBR.05023-11","article-title":"Viral quasispecies evolution","volume":"76","author":"Domingo","year":"2012","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6967","DOI":"10.1073\/pnas.97.13.6967","article-title":"The evolution of RNA viruses: A population genetics view","volume":"97","author":"Moya","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s12011-021-02716-z","article-title":"A Comprehensive Review on Selenium and Its Effects on Human Health and Distribution in Middle Eastern Countries","volume":"200","author":"Kieliszek","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1128\/CMR.00072-15","article-title":"Zika Virus","volume":"29","author":"Musso","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1056\/NEJMra1602113","article-title":"Zika Virus","volume":"374","author":"Petersen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nature04388","article-title":"Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population","volume":"439","author":"Vignuzzi","year":"2006","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1038\/s41598-017-02652-w","article-title":"Quasispecies composition and evolution of a typical Zika virus clinical isolate from Suriname","volume":"7","author":"Tas","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"16038","DOI":"10.1073\/pnas.1111650108","article-title":"Arbovirus high fidelity variant loses fitness in mosquitoes and mice","volume":"108","author":"Coffey","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.chom.2016.03.002","article-title":"Genetic Drift during Systemic Arbovirus Infection of Mosquito Vectors Leads to Decreased Relative Fitness during Host Switching","volume":"19","author":"Grubaugh","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1056\/NEJMoa1602412","article-title":"Zika Virus Infection in Pregnant Women in Rio de Janeiro","volume":"375","author":"Brasil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/S0140-6736(16)00562-6","article-title":"Guillain-Barre 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_42","doi-asserted-by":"crossref","first-page":"837","DOI":"10.3201\/eid2804.211949","article-title":"Zika Virus after the Public Health Emergency of International Concern Period, Brazil","volume":"28","author":"Yakob","year":"2022","journal-title":"Emerg. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1056\/NEJMra1808246","article-title":"Zika Virus Infection\u2014After the Pandemic","volume":"381","author":"Musso","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S135","DOI":"10.1111\/j.1753-4887.1998.tb01631.x","article-title":"Micronutrient status in relationship to mortality in HIV-1 disease","volume":"56","author":"Baum","year":"1998","journal-title":"Nutr. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e0162424","DOI":"10.1128\/spectrum.01624-24","article-title":"Improved Zika virus plaque assay using Vero\/TMPRSS2 cell line","volume":"13","author":"Oluwasemowo","year":"2025","journal-title":"Microbiol. Spectr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1096\/fj.01-0108com","article-title":"Host nutritional selenium status as a driving force for Influenza virus mutations","volume":"15","author":"Nelson","year":"2001","journal-title":"FASEB J."},{"key":"ref_47","unstructured":"Ross, A.C., Caballero, B., Cousins, R.J., Tucker, K.L., and Ziegler, T.R. (2016). Selenium. Modern Nutrition in Health and Disease, Wolters Kluwer. [11th ed.]."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"EFSA NDA Panel (EFSA Panel on Dietetic Products, N.a.A.) (2014). Scientific Opinion on Dietary Reference Values for selenium. EFSA J., 12, 3846.","DOI":"10.2903\/j.efsa.2014.3846"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/imm.12883","article-title":"Using immunocompromised mice to identify mechanisms of Zika virus transmission and pathogenesis","volume":"153","author":"Winkler","year":"2018","journal-title":"Immunology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"veaa092","DOI":"10.1093\/ve\/veaa092","article-title":"Mapping the evolutionary landscape of Zika virus infection in immunocompromised mice","volume":"6","author":"Johnson","year":"2020","journal-title":"Virus Evol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1128\/IAI.01017-10","article-title":"The pathogenicity of an enteric Citrobacter rodentium Infection is enhanced by deficiencies in the antioxidants selenium and vitamin E","volume":"79","author":"Smith","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.3201\/eid1408.080287","article-title":"Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007","volume":"14","author":"Lanciotti","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e28700","DOI":"10.1002\/jmv.28700","article-title":"Performance assessment and validation of a plaque reduction neutralization test (PRNT) in support to yellow fever diagnostic and vaccine clinical trials","volume":"95","author":"Dia","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/nprot.2017.066","article-title":"Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples","volume":"12","author":"Quick","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13059-018-1618-7","article-title":"An amplicon-based sequencing framework for accurately measuring intrahost virus diversity using PrimalSeq and iVar","volume":"20","author":"Grubaugh","year":"2019","journal-title":"Genome Biol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kimbrel, J., Moon, J., Avila-Herrera, A., Marti, J.M., Thissen, J., Mulakken, N., Sandholtz, S.H., Ferrell, T., Daum, C., and Hall, S. (2022). Multiple Mutations Associated with Emergent Variants Can Be Detected as Low-Frequency Mutations in Early SARS-CoV-2 Pandemic Clinical Samples. Viruses, 14.","DOI":"10.3390\/v14122775"},{"key":"ref_57","unstructured":"R Core Team (2023). R: A Language and Environment for Statistical Computing, 4.5.0., R Foundation for Statistical Computing."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1007\/PL00000664","article-title":"The glutathione peroxidases","volume":"57","author":"Arthur","year":"2001","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.chom.2016.03.010","article-title":"A Mouse Model of Zika Virus Pathogenesis","volume":"19","author":"Lazear","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Aliota, M.T., Caine, E.A., Walker, E.C., Larkin, K.E., Camacho, E., and Osorio, J.E. (2016). Characterization of Lethal Zika Virus Infection in AG129 Mice. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004750"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nm0595-433","article-title":"Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates","volume":"1","author":"Beck","year":"1995","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ball, E.E., Pesavento, P.A., Van Rompay, K.K.A., Keel, M.K., Singapuri, A., Gomez-Vazquez, J.P., Dudley, D.M., O\u2019Connor, D.H., Breitbach, M.E., and Maness, N.J. (2022). Zika virus persistence in the male macaque reproductive tract. PLoS Negl. Trop. Dis., 16.","DOI":"10.1101\/2022.03.03.482872"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3201\/eid2303.161499","article-title":"Zika Virus RNA Replication and Persistence in Brain and Placental Tissue","volume":"23","author":"Bhatnagar","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1016\/j.celrep.2017.01.056","article-title":"Frequent Zika Virus Sexual Transmission and Prolonged Viral RNA Shedding in an Immunodeficient Mouse Model","volume":"18","author":"Duggal","year":"2017","journal-title":"Cell Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e2113015118","DOI":"10.1073\/pnas.2113015118","article-title":"A mutation-mediated evolutionary adaptation of Zika virus in mosquito and mammalian host","volume":"118","author":"Yu","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1126\/science.aam7120","article-title":"A single mutation in the prM protein of Zika virus contributes to fetal microcephaly","volume":"358","author":"Yuan","year":"2017","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Aziz, A., Suleman, M., Shah, A., Ullah, A., Rashid, F., Khan, S., Iqbal, A., Luo, S., Xie, L., and Xie, Z. (2023). Comparative mutational analysis of the Zika virus genome from different geographical locations and its effect on the efficacy of Zika virus-specific neutralizing antibodies. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1098323"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.00618-20","article-title":"Two Genetic Differences between Closely Related Zika Virus Strains Determine Pathogenic Outcome in Mice","volume":"94","author":"Carbaugh","year":"2020","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.virs.2022.01.021","article-title":"A single nonsynonymous mutation on ZIKV E protein-coding sequences leads to markedly increased neurovirulence in vivo","volume":"37","author":"Liu","year":"2022","journal-title":"Virol. Sin."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Collette, N.M., Lao, V.H.I., Weilhammer, D.R., Zingg, B., Cohen, S.D., Hwang, M., Coffey, L.L., Grady, S.L., Zemla, A.T., and Borucki, M.K. (2020). Single Amino Acid Mutations Affect Zika Virus Replication In Vitro and Virulence In Vivo. Viruses, 12.","DOI":"10.3390\/v12111295"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/iub.1976","article-title":"Regulatory role of vitamin E in the immune system and inflammation","volume":"71","author":"Lewis","year":"2019","journal-title":"IUBMB Life"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Lee, G.Y., and Han, S.N. (2018). The Role of Vitamin E in Immunity. Nutrients, 10.","DOI":"10.3390\/nu10111614"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1146\/annurev-immunol-042617-053142","article-title":"Immune Response to Dengue and Zika","volume":"36","author":"Ngono","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Doaei, S., Mardi, A., and Zare, M. (2023). Role of micronutrients in the modulation of immune system and platelet activating factor in patients with COVID-19; a narrative review. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1207237"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Pecora, F., Persico, F., Argentiero, A., Neglia, C., and Esposito, S. (2020). The Role of Micronutrients in Support of the Immune Response against Viral Infections. Nutrients, 12.","DOI":"10.3390\/nu12103198"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.immuni.2006.08.007","article-title":"Type I interferons in host defense","volume":"25","author":"Stetson","year":"2006","journal-title":"Immunity"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons in infectious disease","volume":"15","author":"McNab","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-virology-092818-015756","article-title":"Interferon-Stimulated Genes: What Do They All Do?","volume":"6","author":"Schoggins","year":"2019","journal-title":"Annu. Rev. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1093\/jn\/131.6.1798","article-title":"Combined selenium and vitamin E deficiency causes fatal myopathy in guinea pigs","volume":"131","author":"Hill","year":"2001","journal-title":"J. Nutr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1079\/BJN20041110","article-title":"Selenium and iodine intakes and status in New Zealand and Australia","volume":"91","author":"Thomson","year":"2004","journal-title":"Br. J. Nutr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1093\/jn\/138.1.130","article-title":"The immune response to herpes simplex virus encephalitis in mice is modulated by dietary vitamin E","volume":"138","author":"Sheridan","year":"2008","journal-title":"J. Nutr."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1089\/ars.2011.4145","article-title":"The role of selenium in inflammation and immunity: From molecular mechanisms to therapeutic opportunities","volume":"16","author":"Huang","year":"2012","journal-title":"Antioxid. Redox Signal"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1007\/s12035-023-03761-6","article-title":"Molecular Mechanisms Associated with Neurodegeneration of Neurotropic Viral Infection","volume":"61","author":"Wongchitrat","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1038\/s41598-020-57914-x","article-title":"Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes","volume":"10","author":"Ledur","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"198084","DOI":"10.1016\/j.virusres.2020.198084","article-title":"Zika virus induces oxidative stress and decreases antioxidant enzyme activities in vitro and in vivo","volume":"286","author":"Almeida","year":"2020","journal-title":"Virus Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1096\/fasebj.13.10.1145","article-title":"Vitamin E: Function and metabolism","volume":"13","author":"Traber","year":"1999","journal-title":"FASEB J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrn2038","article-title":"Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms","volume":"8","author":"Block","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nrn3898","article-title":"Astrocyte barriers to neurotoxic inflammation","volume":"16","author":"Sofroniew","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuron.2008.01.003","article-title":"The blood-brain barrier in health and chronic neurodegenerative disorders","volume":"57","author":"Zlokovic","year":"2008","journal-title":"Neuron"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0301-0082(99)00060-X","article-title":"Metabolism and functions of glutathione in brain","volume":"62","author":"Dringen","year":"2000","journal-title":"Prog. Neurobiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.immuni.2019.03.025","article-title":"Shared and Distinct Functions of Type I and Type III Interferons","volume":"50","author":"Lazear","year":"2019","journal-title":"Immunity"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/path.2287","article-title":"TNF-mediated inflammatory disease","volume":"214","author":"Bradley","year":"2008","journal-title":"J. Pathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1189\/jlb.0603252","article-title":"Interferon-gamma: An overview of signals, mechanisms and functions","volume":"75","author":"Schroder","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"20181","DOI":"10.1074\/jbc.M802559200","article-title":"Selenoproteins mediate T cell immunity through an antioxidant mechanism","volume":"283","author":"Shrimali","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e0258224","DOI":"10.1128\/mbio.02582-24","article-title":"Interference without interferon: Interferon-independent induction of interferon-stimulated genes and its role in cellular innate immunity","volume":"15","author":"Swaraj","year":"2024","journal-title":"mBio"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e2166","DOI":"10.1002\/rmv.2166","article-title":"The innate immune response in Zika virus infection","volume":"31","author":"Azevedo","year":"2021","journal-title":"Rev. Med. Virol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41586-023-06816-9","article-title":"Dictionary of immune responses to cytokines at single-cell resolution","volume":"625","author":"Cui","year":"2024","journal-title":"Nature"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1126\/science.8009221","article-title":"Functional role of type I and type II interferons in antiviral defense","volume":"264","author":"Steinhoff","year":"1994","journal-title":"Science"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Hiffler, L., and Rakotoambinina, B. (2020). Selenium and RNA Virus Interactions: Potential Implications for SARS-CoV-2 Infection (COVID-19). Front. Nutr., 7.","DOI":"10.3389\/fnut.2020.00164"},{"key":"ref_100","unstructured":"Graham, M.E., Oluwasemowo, O.O., Murugesh, D.K., Avila-Herrera, A., Kimbrel, J.A., Thissen, J.B., Zemla, A., Phillips, A.M., Collette, N.M., and Weilhammer, D.R. (2025, January 14\u201317). Impacts of Climate-drive Host Selenium Status on SARS-CoV-2 Pathogenesis and Variant Emergence. Proceedings of the 44th Annual Meeting, American Society for Virology, Montreal, QC, Canada."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1056\/NEJMsr1604338","article-title":"Zika Virus and Birth Defects\u2014Reviewing the Evidence for Causality","volume":"374","author":"Rasmussen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1056\/NEJMoa1600651","article-title":"Zika Virus Associated with Microcephaly","volume":"374","author":"Mlakar","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e01605","DOI":"10.1128\/JVI.01605-20","article-title":"Two Sides of a Coin: A Zika Virus Mutation Selected in Pregnant Rhesus Macaques Promotes Fetal Infection in Mice but at a Cost of Reduced Fitness in Nonpregnant Macaques and Diminished Transmissibility by Vectors","volume":"94","author":"Lemos","year":"2020","journal-title":"J. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.tim.2004.07.007","article-title":"Host nutritional status: The neglected virulence factor","volume":"12","author":"Beck","year":"2004","journal-title":"Trends Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"vom Steeg, L.G., and Klein, S.L. (2016). SeXX Matters in Infectious Disease Pathogenesis. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005374"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.00623-17","article-title":"Zika Virus Infects Human Sertoli Cells and Modulates the Integrity of the In Vitro Blood-Testis Barrier Model","volume":"91","author":"Siemann","year":"2017","journal-title":"J. Virol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.cell.2016.11.016","article-title":"Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice","volume":"167","author":"Ma","year":"2016","journal-title":"Cell"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.virol.2019.02.004","article-title":"Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice","volume":"530","author":"Duggal","year":"2019","journal-title":"Virology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1007\/s13238-016-0275-4","article-title":"The crystal structure of Zika virus helicase: Basis for antiviral drug design","volume":"7","author":"Tian","year":"2016","journal-title":"Protein Cell"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/2\/177\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T05:13:41Z","timestamp":1770441221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/2\/177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":110,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["v18020177"],"URL":"https:\/\/doi.org\/10.3390\/v18020177","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]}}}