{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:42:30Z","timestamp":1792806150326,"version":"4.5.0"},"reference-count":116,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RCMI Program in Health Disparities Research at Meharry Medical College","award":["NIH U54MD007586"],"award-info":[{"award-number":["NIH U54MD007586"]}],"id":[{"id":"https:\/\/ror.org\/00k63dq23","id-type":"ROR","asserted-by":"crossref"}]},{"name":"RCMI Program in Health Disparities Research at Meharry Medical College","award":["NIH P30AI110527"],"award-info":[{"award-number":["NIH P30AI110527"]}],"id":[{"id":"https:\/\/ror.org\/00k63dq23","id-type":"ROR","asserted-by":"crossref"}]},{"name":"RCMI Program in Health Disparities Research at Meharry Medical College","award":["NIH SC1GM089269"],"award-info":[{"award-number":["NIH SC1GM089269"]}],"id":[{"id":"https:\/\/ror.org\/00k63dq23","id-type":"ROR","asserted-by":"crossref"}]},{"name":"RCMI Program in Health Disparities Research at Meharry Medical College","award":["NIH R25GM059994"],"award-info":[{"award-number":["NIH R25GM059994"]}],"id":[{"id":"https:\/\/ror.org\/00k63dq23","id-type":"ROR","asserted-by":"crossref"}]},{"name":"RCMI Program in Health Disparities Research at Meharry Medical College","award":["NIH T32HL007737"],"award-info":[{"award-number":["NIH T32HL007737"]}],"id":[{"id":"https:\/\/ror.org\/00k63dq23","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Tennessee Center for AIDS Research (TN-CFAR)","award":["NIH U54MD007586"],"award-info":[{"award-number":["NIH U54MD007586"]}],"id":[{"id":"https:\/\/ror.org\/05n52x113","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Tennessee Center for AIDS Research (TN-CFAR)","award":["NIH P30AI110527"],"award-info":[{"award-number":["NIH P30AI110527"]}],"id":[{"id":"https:\/\/ror.org\/05n52x113","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Tennessee Center for AIDS Research (TN-CFAR)","award":["NIH SC1GM089269"],"award-info":[{"award-number":["NIH SC1GM089269"]}],"id":[{"id":"https:\/\/ror.org\/05n52x113","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Tennessee Center for AIDS Research (TN-CFAR)","award":["NIH R25GM059994"],"award-info":[{"award-number":["NIH R25GM059994"]}],"id":[{"id":"https:\/\/ror.org\/05n52x113","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Tennessee Center for AIDS Research (TN-CFAR)","award":["NIH T32HL007737"],"award-info":[{"award-number":["NIH T32HL007737"]}],"id":[{"id":"https:\/\/ror.org\/05n52x113","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Meharry RISE Initiative","award":["NIH U54MD007586"],"award-info":[{"award-number":["NIH U54MD007586"]}]},{"name":"Meharry RISE Initiative","award":["NIH P30AI110527"],"award-info":[{"award-number":["NIH P30AI110527"]}]},{"name":"Meharry RISE Initiative","award":["NIH SC1GM089269"],"award-info":[{"award-number":["NIH SC1GM089269"]}]},{"name":"Meharry RISE Initiative","award":["NIH R25GM059994"],"award-info":[{"award-number":["NIH R25GM059994"]}]},{"name":"Meharry RISE Initiative","award":["NIH T32HL007737"],"award-info":[{"award-number":["NIH T32HL007737"]}]},{"name":"T-32 Research Training in Cardiovascular Biology at Meharry grant","award":["NIH U54MD007586"],"award-info":[{"award-number":["NIH U54MD007586"]}]},{"name":"T-32 Research Training in Cardiovascular Biology at Meharry grant","award":["NIH P30AI110527"],"award-info":[{"award-number":["NIH P30AI110527"]}]},{"name":"T-32 Research Training in Cardiovascular Biology at Meharry grant","award":["NIH SC1GM089269"],"award-info":[{"award-number":["NIH SC1GM089269"]}]},{"name":"T-32 Research Training in Cardiovascular Biology at Meharry grant","award":["NIH R25GM059994"],"award-info":[{"award-number":["NIH R25GM059994"]}]},{"name":"T-32 Research Training in Cardiovascular Biology at Meharry grant","award":["NIH T32HL007737"],"award-info":[{"award-number":["NIH T32HL007737"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Zika virus (ZIKV) is an emerging flavivirus that causes congenital birth defects and neurological compilations in the human host. Although ZIKV is primarily transmitted through infected mosquitos, recent studies reveal sexual contact as a potential transmission route. In vagina-bearing individuals, the vaginal epithelium constitutes the first line of defense against viruses. However, it is unclear how ZIKV interacts with the vaginal epithelium to initiate ZIKV transmission. In this study, we demonstrate that exposing ZIKV to human vaginal epithelial cells (hVECs) resulted in de novo viral RNA replication, increased envelope viral protein production, and a steady, extracellular release of infectious viral particles. Interestingly, our data show that, despite an increase in viral load, the hVECs did not exhibit significant cytopathology in culture as other cell types typically do. Furthermore, our data reveal that the innate antiviral state of hVECs plays a crucial role in preventing viral cytopathology. For the first time, our data show that interferon epsilon inhibits ZIKV replication. Collectively, our results in this study provide a novel perspective on the viral susceptibility and replication dynamics during ZIKV infection in the human vaginal epithelium. These findings will be instrumental towards developing therapeutic agents aimed at eliminating the pathology caused by the virus.<\/jats:p>","DOI":"10.3390\/pathogens11080853","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T04:04:00Z","timestamp":1659326640000},"page":"853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Interferon Epsilon Signaling Confers Attenuated Zika Replication in Human Vaginal Epithelial Cells"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-7862","authenticated-orcid":false,"suffix":"Jr.","given":"James W.","family":"Mungin","sequence":"first","affiliation":[{"name":"Centers for AIDS Health Disparity Research, Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN 37208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Centers for AIDS Health Disparity Research, Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN 37208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bindong","family":"Liu","sequence":"additional","affiliation":[{"name":"Centers for AIDS Health Disparity Research, Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN 37208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jneuroim.2017.03.001","article-title":"Zika virus: History, epidemiology, transmission, and clinical presentation","volume":"308","author":"Song","year":"2017","journal-title":"J. Neuroimmunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1139\/cjm-2019-0331","article-title":"Zika virus: An emerging challenge to public health worldwide","volume":"66","author":"Sharma","year":"2020","journal-title":"Can. J. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/tmi.13216","article-title":"Zika transmission patterns: A meta-review","volume":"24","author":"Morrison","year":"2019","journal-title":"Trop. Med. Int. Health"},{"key":"ref_4","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_5","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_6","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.virusres.2017.07.025","article-title":"Zika virus research models","volume":"254","author":"Kublin","year":"2018","journal-title":"Virus Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S868","DOI":"10.1093\/infdis\/jix434","article-title":"Epidemiology of Zika Virus Infection","volume":"216","author":"Hills","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1007\/s10815-017-0988-1","article-title":"Impact of Zika virus for infertility specialists: Current literature, guidelines, and resources","volume":"34","author":"Dubaut","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17055","DOI":"10.1038\/s41598-019-53062-z","article-title":"Impact of weather seasonality and sexual transmission on the spread of Zika fever","volume":"9","author":"Denes","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12978-017-0285-6","article-title":"Zika virus infection in pregnancy: A systematic review of disease course and complications","volume":"14","author":"Chibueze","year":"2017","journal-title":"Reprod. Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.micinf.2018.01.006","article-title":"An overview of mosquito vectors of Zika virus","volume":"20","author":"Boyer","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1021\/acs.chemrev.7b00719","article-title":"Biochemistry and Molecular Biology of Flaviviruses","volume":"118","author":"Barrows","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"606","DOI":"10.2105\/AJPH.2016.303112","article-title":"History, Epidemiology, and Clinical Manifestations of Zika: A Systematic Review","volume":"106","author":"Paixao","year":"2016","journal-title":"Am. J. Public Health"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"402","DOI":"10.2471\/BLT.17.201541","article-title":"Prevalence of asymptomatic Zika virus infection: A systematic review","volume":"96","author":"Haby","year":"2018","journal-title":"Bull. World Health Organ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1053\/j.semperi.2018.02.003","article-title":"Adverse outcomes of pregnancy-associated Zika virus infection","volume":"42","author":"Britt","year":"2018","journal-title":"Semin. Perinatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5092","DOI":"10.3934\/mbe.2019256","article-title":"Implication of sexual transmission of Zika on dengue and Zika outbreaks","volume":"16","author":"Tang","year":"2019","journal-title":"Math. Biosci. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Stassen, L., Armitage, C.W., van der Heide, D.J., Beagley, K.W., and Frentiu, F.D. (2018). Zika Virus in the Male Reproductive Tract. Viruses, 10.","DOI":"10.3390\/v10040198"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sakkas, H., Bozidis, P., Giannakopoulos, X., Sofikitis, N., and Papadopoulou, C. (2018). An Update on Sexual Transmission of Zika Virus. Pathogens, 7.","DOI":"10.3390\/pathogens7030066"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3201\/eid2301.161394","article-title":"Prolonged Detection of Zika Virus in Vaginal Secretions and Whole Blood","volume":"23","author":"Murray","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.cmi.2016.12.027","article-title":"Sexually acquired Zika virus: A systematic review","volume":"23","author":"Moreira","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"McDonald, E.M., Duggal, N.K., and Brault, A.C. (2017). Pathogenesis and sexual transmission of Spondweni and Zika viruses. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005990"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"i6500","DOI":"10.1136\/bmj.i6500","article-title":"First case of Zika virus spread through sexual contact is detected in UK","volume":"355","author":"Gulland","year":"2016","journal-title":"BMJ"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S875","DOI":"10.1093\/infdis\/jix396","article-title":"Modes of Transmission of Zika Virus","volume":"216","author":"Gregory","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_25","first-page":"325","article-title":"Zika Virus and Sexual Transmission: A New Route of Transmission for Mosquito-borne Flaviviruses","volume":"90","author":"Hastings","year":"2017","journal-title":"Yale J. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7253","DOI":"10.1038\/s41598-019-43651-3","article-title":"Understanding the survival of Zika virus in a vector interconnected sexual contact network","volume":"9","author":"Ferdousi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Counotte, M.J., Kim, C.R., Wang, J., Bernstein, K., Deal, C.D., Broutet, N.J.N., and Low, N. (2018). Sexual transmission of Zika virus and other flaviviruses: A living systematic review. PLoS Med., 15.","DOI":"10.1371\/journal.pmed.1002611"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Blitvich, B.J., Magalhaes, T., Laredo-Tiscare\u00f1o, S.V., and Foy, B.D. (2020). Sexual Transmission of Arboviruses: A Systematic Review. Viruses, 12.","DOI":"10.3390\/v12090933"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Allard, A., Althouse, B.M., H\u00e9bert-Dufresne, L., and Scarpino, S.V. (2017). The risk of sustained sexual transmission of Zika is underestimated. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006633"},{"key":"ref_30","unstructured":"(2019). WHO Guidelines for the Prevention of Sexual Transmission of Zika Virus: Executive Summary, World Health Organization (WHO)."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7176","DOI":"10.1038\/s41598-017-07099-7","article-title":"Sexual and Vertical Transmission of Zika Virus in anti-interferon receptor-treated Rag1-deficient mice","volume":"7","author":"Winkler","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"574054","DOI":"10.3389\/fmicb.2020.574054","article-title":"Potent Restriction of Sexual Zika Virus Infection by the Lipid Fraction of Extracellular Vesicles in Semen","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1080\/22221751.2021.1932606","article-title":"Extracellular acidosis enhances Zika virus infection both in human cells and ex-vivo tissue cultures from female re-productive tract","volume":"10","author":"Varese","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1093\/infdis\/jix204","article-title":"Fetal Growth Restriction Caused by Sexual Transmission of Zika Virus in Mice","volume":"215","author":"Uraki","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1016\/j.celrep.2016.11.070","article-title":"A Mouse Model of Zika Virus Sexual Transmission and Vaginal Viral Replication","volume":"17","author":"Tang","year":"2016","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e01372-19","DOI":"10.1128\/mBio.01372-19","article-title":"Axl Promotes Zika Virus Entry and Modulates the Antiviral State of Human Sertoli Cells","volume":"10","author":"Strange","year":"2019","journal-title":"mBio"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1093\/infdis\/jix436","article-title":"Replication of Zika Virus in Human Prostate Cells: A Potential Source of Sexually Transmitted Virus","volume":"217","author":"Spencer","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e00623-17","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_39","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.3389\/fmicb.2019.02250","article-title":"A Peptide-Based Virus Inactivator Protects Male Mice Against Zika Virus-Induced Damage of Testicular Tissue","volume":"10","author":"Si","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00038-18","DOI":"10.1128\/JVI.00038-18","article-title":"Cellular and Humoral Immunity Protect against Vaginal Zika Virus Infection in Mice","volume":"92","author":"Scott","year":"2018","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1038\/s41467-018-04444-w","article-title":"Male germ cells support long-term propagation of Zika virus","volume":"9","author":"Robinson","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e01434-19","DOI":"10.1128\/JVI.01434-19","article-title":"Zika Virus Infection, Reproductive Organ Targeting, and Semen Transmission in the Male Olive Baboon","volume":"94","author":"Peregrine","year":"2019","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"44286","DOI":"10.1038\/srep44286","article-title":"Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus","volume":"7","author":"Pagani","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1038\/s41467-018-04442-y","article-title":"Semen inhibits Zika virus infection of cells and tissues from the anogenital region","volume":"9","author":"Muller","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3390\/v11010042","article-title":"Differential Zika Virus Infection of Testicular Cell Lines","volume":"11","author":"Mlera","year":"2019","journal-title":"Viruses"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2019.06.010","article-title":"Duration of seminal Zika viral RNA shedding in immunocompetent mice inoculated with Asian and African genotype viruses","volume":"535","author":"McDonald","year":"2019","journal-title":"Virology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4697","DOI":"10.1172\/JCI121735","article-title":"Zika virus infects human testicular tissue and germ cells","volume":"128","author":"Matusali","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1038\/s41598-018-23899-x","article-title":"Human Sertoli cells support high levels of Zika virus replication and persistence","volume":"8","author":"Kumar","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hubert, M., Chiche, A., Legros, V., Jeannin, P., Montange, T., Gessain, A., Ceccaldi, P., and Vidy, A. (2019). Productive Infection of Mouse Mammary Glands and Human Mammary Epithelial Cells by Zika Virus. Viruses, 11.","DOI":"10.3390\/v11100950"},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"4510","DOI":"10.1038\/s41598-018-22840-6","article-title":"Sexual transmission of Zika virus enhances in utero transmission in a mouse model","volume":"8","author":"Duggal","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41467-018-07993-2","article-title":"Interferon lambda protects the female reproductive tract against Zika virus infection","volume":"10","author":"Caine","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_53","first-page":"3340","article-title":"Cultivated Human Vaginal Microbiome Communities Impact Zika and Herpes Simplex Virus Replication in ex vivo Vaginal Mucosal Cultures","volume":"9","author":"Miller","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_54","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_55","doi-asserted-by":"crossref","first-page":"825049","DOI":"10.3389\/fmicb.2021.825049","article-title":"HSV-2 Infection Enhances Zika Virus Infection of Primary Genital Epithelial Cells Independently of the Known Zika Virus Receptor AXL","volume":"12","author":"Gornalusse","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Carroll, T., Lo, M., Lanteri, M., Dutra, J., Zarbock, K., Silveira, P., Rourke, T., Ma, Z., Fritts, L., and O\u2019Connor, S. (2017). Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006537"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.cell.2016.05.008","article-title":"Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise","volume":"165","author":"Miner","year":"2016","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.cell.2016.08.004","article-title":"Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection","volume":"166","author":"Yockey","year":"2016","journal-title":"Cell"},{"key":"ref_59","first-page":"392","article-title":"Zika virus replicates in the vagina of mice with 1 intact interferon signaling","volume":"48","author":"Lopez","year":"2022","journal-title":"bioRxiv"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/cmi.2014.41","article-title":"Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection","volume":"11","author":"Nguyen","year":"2014","journal-title":"Cell. Mol. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nri2836","article-title":"Antiviral immune responses in the genital tract: Clues for vaccines","volume":"10","author":"Iwasaki","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kinlock, B.L., Wang, Y., Turner, T.M., Wang, C., and Liu, B. (2014). Transcytosis of HIV-1 through vaginal epithelial cells is dependent on trafficking to the endocytic recycling pathway. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096760"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.it.2021.09.003","article-title":"Differential roles of interferons in innate responses to mucosal viral infections","volume":"42","author":"Walker","year":"2021","journal-title":"Trends Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1172\/JCI136225","article-title":"Herpesvirus latency","volume":"130","author":"Cohen","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1128\/CMR.05028-11","article-title":"Epithelial cell responses to infection with human papillomavirus","volume":"25","author":"Stanley","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s40168-016-0203-0","article-title":"The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: What do we know and where are we going next?","volume":"4","author":"Mitra","year":"2016","journal-title":"Microbiome"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3389\/fimmu.2019.00208","article-title":"Oral Mucosal Epithelial Cells","volume":"10","author":"Groeger","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1016\/j.celrep.2016.05.074","article-title":"The IFITMs Inhibit Zika Virus Replication","volume":"15","author":"Savidis","year":"2016","journal-title":"Cell Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/s41564-019-0421-x","article-title":"Decoding type I and III interferon signalling during viral infection","volume":"4","author":"Mesev","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1159\/000495897","article-title":"Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection","volume":"51","author":"Li","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.15252\/embr.201642627","article-title":"Zika virus inhibits type-I interferon production and downstream signaling","volume":"17","author":"Kumar","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.chom.2016.05.009","article-title":"Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling","volume":"19","author":"Grant","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.bbrc.2017.05.146","article-title":"Antagonism of type I interferon by flaviviruses","volume":"492","author":"Miorin","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Thurmond, S., Wang, B., Song, J., and Hai, R. (2018). Suppression of Type I Interferon Signaling by Flavivirus NS5. Viruses, 10.","DOI":"10.3390\/v10120712"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/mi.2012.35","article-title":"Role of novel type I interferon epsilon in viral infection and mucosal immunity","volume":"5","author":"Xi","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e88255","DOI":"10.1172\/jci.insight.88255","article-title":"IFN-epsilon protects primary macrophages against HIV infection","volume":"1","author":"Tasker","year":"2016","journal-title":"JCI Insight"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1074\/jbc.M117.800755","article-title":"Defining the distinct, intrinsic properties of the novel type I interferon Epsilon","volume":"293","author":"Stifter","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.pep.2006.12.013","article-title":"Purification of recombinant human interferon-epsilon and oligonucleotide microarray analysis of interfer-on-epsilon-regulated genes","volume":"53","author":"Peng","year":"2007","journal-title":"Protein Expr. Purif."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.4049\/jimmunol.1201925","article-title":"Novel role for molecular transporter importin 9 in posttranscriptional regulation of IFN-epsilon expression","volume":"191","author":"Matsumiya","year":"2013","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4542","DOI":"10.4049\/jimmunol.179.7.4542","article-title":"IFN-epsilon mediates TNF-alpha-induced STAT1 phosphorylation and induction of retinoic acid-inducible gene-I in human cervical cancer cells","volume":"179","author":"Matsumiya","year":"2007","journal-title":"J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Hermant, P., Francius, C., Clotman, F., and Michiels, T. (2013). IFN-epsilon is constitutively expressed by cells of the reproductive tract and is inefficiently secreted by fibroblasts and cell lines. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071320"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"16057","DOI":"10.1074\/jbc.RA118.003617","article-title":"Human interferon- and interferon-kappa exhibit low potency and low affinity for cell-surface IFNAR and the poxvirus antagonist B18R","volume":"293","author":"Harris","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1189\/jlb.3A0214-088RRR","article-title":"The mucosal expression pattern of interferon-epsilon in rhesus macaques","volume":"96","author":"Demers","year":"2014","journal-title":"J. Leukoc. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7158","DOI":"10.4049\/jimmunol.180.11.7158","article-title":"Differential effects of the type I interferons alpha4, beta, and epsilon on antiviral activity and vaccine efficacy","volume":"180","author":"Day","year":"2008","journal-title":"J. Immunol."},{"key":"ref_85","first-page":"1979","article-title":"Interferon epsilon mRNA expression could represent a potential molecular marker in cervical cancer","volume":"11","author":"Mantilla","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Bourke, N.M., Achilles, S.L., Huang, S.U., Cumming, H.E., Papageorgio, I., Gearing, L.J., Thakore, S., Mangan, N.E., Mesiano, S., and Hertzog, P.J. (2018). Human IFN\u03b5: Spaciotemporal expression, hormone regulation and innate immunity in the female reproductive tract. bioRxiv Prepr.","DOI":"10.1101\/445007"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"103154","DOI":"10.1016\/j.jri.2020.103154","article-title":"SARS-CoV-2 (Covid-19): Interferon-epsilon may be responsible of decreased mortality in females","volume":"141","author":"Afsar","year":"2020","journal-title":"J. Reprod. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/mi.2015.116","article-title":"Linn, K.A. HIV-1-negative female sex workers sustain high cervical IFN epsilon, low immune activation, and low expression of HIV-1-required host genes","volume":"9","author":"Abdulhaqq","year":"2016","journal-title":"Mucosal Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1126\/science.1233321","article-title":"Interferon-epsilon protects the female reproductive tract from viral and bacterial infection","volume":"339","author":"Fung","year":"2013","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1095\/biolreprod57.4.847","article-title":"Generation of Papillomavirus-lmmortalized Cell Lines from Normal Human Ectocervical, Endocervical, and Vaginal Epithelium That Maintain Expression of Tissue-Specific Differentiation Proteins","volume":"57","author":"Raina","year":"1997","journal-title":"Biol. Reprod."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s40588-019-00116-5","article-title":"The complexity of interactions between female sex hormones and Chlamydia trachomatis infections","volume":"6","author":"Berry","year":"2019","journal-title":"Curr. Clin. Microbiol. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1136\/bmj.323.7309.394","article-title":"Hormonal markers of susceptibility to sexually transmitted infections: Are we taking them seriously?","volume":"323","author":"Brabin","year":"2001","journal-title":"Br. Med. J."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Jia, X., Shao, Q., Chaudhry, A.R., Kinlock, B.L., Izban, M.G., Zhang, H., Villalta, F., Hildreth, J.E.K., and Liu, B. (2021). Medroxyprogesterone Acetate (MPA) Enhances HIV-1 Accumulation and Release in Primary Cervical Epithelial Cells by Inhibiting Lysosomal Activity. Pathogens, 10.","DOI":"10.3390\/pathogens10091192"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.1600-0897.2010.00842.x","article-title":"Sex hormone regulation of innate immunity in the female reproductive tract: The role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens","volume":"63","author":"Wira","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Sherman, K.E., Rouster, S.D., Kong, L.X., Aliota, M.T., Blackard, J.T., and Dean, G.E. (2019). Zika virus replication and cytopathic effects in liver cells. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214016"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Stefanik, M., Formanova, P., Bily, T., Vancova, M., Eyer, L., Palus, M., Salat, J., Braconi, C.T., Zanotto, P.M., and Gould, A.E. (2018). Characterisation of Zika virus infection in primary human astrocytes. BMC Neurosci., 19.","DOI":"10.1186\/s12868-018-0407-2"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"14543","DOI":"10.1038\/s41598-018-32400-7","article-title":"Differentiation enhances Zika virus infection of neuronal brain cells","volume":"8","author":"Li","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e02144-16","DOI":"10.1128\/JVI.02144-16","article-title":"Zika Virus Efficiently Replicates in Human Retinal Epithelium and Disturbs Its Permeability","volume":"91","author":"Salinas","year":"2017","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Rossi, F., Josey, B., Sayitoglu, E.C., Potens, R., Sultu, T., Duru, A.D., and Beljanski, V. (2020). Characterization of zika virus infection of human fetal cardiac mesenchymal stromal cells. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0239238"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12974-017-0824-7","article-title":"Zika virus infection of cellular components of the blood-retinal barriers: Implications for viral associated congenital ocular disease","volume":"14","author":"Roach","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Peng, H., Liu, B., Yves, T.D., He, Y., Wang, S., Tang, H., Ren, H., Zhao, P., Qi, Z., and Qin, Z. (2018). Zika Virus Induces Autophagy in Human Umbilical Vein Endothelial Cells. Viruses, 10.","DOI":"10.3390\/v10050259"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.15252\/embj.201695597","article-title":"Zika virus induces massive cytoplasmic vacuolization and paraptosis-like death in infected cells","volume":"36","author":"Monel","year":"2017","journal-title":"EMBO J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e3106","DOI":"10.1038\/cddis.2017.517","article-title":"Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells","volume":"8","author":"Devhare","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1038\/emi.2016.99","article-title":"Differential cell line susceptibility to the emerging Zika virus: Implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs","volume":"5","author":"Chan","year":"2016","journal-title":"Emerg. Microbes Infect."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/nri888","article-title":"Viruses and interferon: A fight for supremacy","volume":"2","author":"Katze","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ygeno.2004.03.003","article-title":"Characterization of the type I interferon locus and identification of novel genes","volume":"84","author":"Hardy","year":"2004","journal-title":"Genomics"},{"key":"ref_107","unstructured":"(2022, July 01). \u201cWhat We Know about Zika and Pregnancy.\u201d CDC: Zika and Pregnancy, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Available online: www.cdc.gov\/pregnancy\/zika\/pregnancy.html."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e00067-20","DOI":"10.1128\/JVI.00067-20","article-title":"Zika Virus Mucosal Infection Provides Protective Immunity","volume":"94","author":"Martinez","year":"2020","journal-title":"J. Virol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"969","DOI":"10.4049\/jimmunol.181.2.969","article-title":"Medroxyprogesterone acetate inhibits CD8+ T cell viral specific effector function and induces herpes simplex virus type 1","volume":"18","author":"Cherpes","year":"2008","journal-title":"J. Immunol."},{"key":"ref_110","unstructured":"Thomas Albrecht, M.F., Boldogh, I., and Alan, S.R. (1996). Medical Microbiology, University of Texas Medical Branch at Galveston. [4th ed.]. Chapter 44."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.virusres.2017.09.006","article-title":"Role of autophagy in Zika virus infection and pathogenesis","volume":"254","author":"Chiramel","year":"2018","journal-title":"Virus Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.chom.2016.03.008","article-title":"Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection","volume":"19","author":"Bayer","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.01050-20","article-title":"TLR3 activation by Zika virus stimulates inflammatory cytokine production which dampens the antiviral response induced by RIG-I-like receptors","volume":"95","author":"Plociennikowska","year":"2021","journal-title":"J. Virol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.3389\/fimmu.2019.01617","article-title":"The Dual Role of the Immune Response in Reproductive Organs During Zika Virus Infection","volume":"10","author":"Cervantes","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e00246-16","DOI":"10.1128\/mSphere.00246-16","article-title":"Rescue of the 1947 Zika Virus Prototype Strain with a Cytomegalovirus Promoter-Driven cDNA Clone","volume":"1","author":"Schwarz","year":"2016","journal-title":"mSphere"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Claire, E., Stewart, R.E., Catherine, R., and Adamson, S. (2014). Inhibitors of the Interferon Response Enhance Virus Replication In Vitro. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112014"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/8\/853\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:58:54Z","timestamp":1760140734000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/8\/853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,29]]},"references-count":116,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["pathogens11080853"],"URL":"https:\/\/doi.org\/10.3390\/pathogens11080853","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,29]]}}}