{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:26:15Z","timestamp":1785432375426,"version":"3.56.0"},"reference-count":80,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI145829"],"award-info":[{"award-number":["R01AI145829"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R01AI145829"],"award-info":[{"award-number":["R01AI145829"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P42ES030991"],"award-info":[{"award-number":["P42ES030991"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"award":["P42ES030991"],"award-info":[{"award-number":["P42ES030991"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of Child Health and Human Development","award":["R01HD111146"],"award-info":[{"award-number":["R01HD111146"]}]},{"DOI":"10.13039\/100022401","name":"Fulbright U.S. Student Program","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100022401","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The role of human leukocyte antigen F (HLA-F) at the maternal\u2013fetal interface (MFI) during viral infection and its regulation by interferon signaling remains poorly understood. Here, we investigated HLA-F expression and regulation in first-trimester trophoblast cells following activation of the type I interferon pathway and viral infection. We demonstrate that HLA-F is significantly upregulated at both mRNA and protein levels in response to Poly(I:C) and IFN-\u03b2 in a dose- and time-dependent manner, suggesting its regulation as an interferon-stimulated gene (ISG). Zika virus (ZIKV) infection similarly induced HLA-F upregulation over time. In contrast, HSV-2 infection downregulated HLA-F mRNA while maintaining steady protein levels, indicative of virus-specific regulatory mechanisms. Moreover, we identified a soluble form of HLA-F secreted following Poly(I:C) stimulation. These findings reveal that HLA-F is dynamically regulated in trophoblasts during viral challenge and type I IFN signaling activation, supporting its broader immunomodulatory role in antiviral defense and immune tolerance at the MFI.<\/jats:p>","DOI":"10.3390\/v18060603","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T11:02:51Z","timestamp":1779793371000},"page":"603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Type I Interferon Regulation of HLA-F Expression in Human Trophoblasts During Viral Infection"],"prefix":"10.3390","volume":"18","author":[{"given":"Diana","family":"Manchorova","sequence":"first","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201, USA"},{"name":"Institute of Biology and Immunology of Reproduction \u201cAcad. Kiril Bratanov\u201d, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7747-2071","authenticated-orcid":false,"given":"Jiahui","family":"Ding","sequence":"additional","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Biochemistry, Microbiology and Immunology, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9178-5813","authenticated-orcid":false,"given":"Annie Thy","family":"Nguyen","sequence":"additional","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201, USA"},{"name":"School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-4352","authenticated-orcid":false,"given":"Tanya","family":"Dimova","sequence":"additional","affiliation":[{"name":"Institute of Biology and Immunology of Reproduction \u201cAcad. Kiril Bratanov\u201d, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7438-0144","authenticated-orcid":false,"given":"Sergey","family":"Slavov","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Department, Medical University, University Obstetrics and Gynecology Hospital \u201cMaichin Dom\u201d, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liubomir","family":"Djerov","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Department, Medical University, University Obstetrics and Gynecology Hospital \u201cMaichin Dom\u201d, 1431 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5499-3912","authenticated-orcid":false,"given":"Gil","family":"Mor","sequence":"additional","affiliation":[{"name":"C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1600-0897.2010.00836.x","article-title":"The immune system in pregnancy: A unique complexity","volume":"63","author":"Mor","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nri.2017.64","article-title":"The unique immunological and microbial aspects of pregnancy","volume":"17","author":"Mor","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1056\/NEJMra000763","article-title":"Implantation and the survival of early pregnancy","volume":"345","author":"Norwitz","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1749-6632.2010.05938.x","article-title":"Inflammation and pregnancy: The role of the immune system at the implantation site","volume":"1221","author":"Mor","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"You, Y., Stelzl, P., Joseph, D.N., Aldo, P.B., Maxwell, A.J., Dekel, N., Liao, A., Whirledge, S., and Mor, G. (2021). TNF-\u03b1 Regulated Endometrial Stroma Secretome Promotes Trophoblast Invasion. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.737401"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.rbmo.2013.08.005","article-title":"The science of implantation emerges blinking into the light","volume":"27","author":"Sharkey","year":"2013","journal-title":"Reprod. Biomed. Online"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0143-4004(83)80043-5","article-title":"Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy","volume":"4","author":"Pijnenborg","year":"1983","journal-title":"Placenta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00418-016-1509-5","article-title":"Extravillous trophoblasts invade more than uterine arteries: Evidence for the invasion of uterine veins","volume":"147","author":"Moser","year":"2017","journal-title":"Histochem. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/humrep\/deq035","article-title":"Endoglandular trophoblast, an alternative route of trophoblast invasion? Analysis with novel confrontation co-culture models","volume":"25","author":"Moser","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e13187","DOI":"10.1111\/aji.13187","article-title":"Trophoblasts promote induction of a regulatory phenotype in B cells that can protect against detrimental T cell-mediated inflammation","volume":"82","author":"Dimova","year":"2019","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1387\/ijdb.082763jb","article-title":"Immune cells in the placental bed","volume":"54","author":"Bulmer","year":"2010","journal-title":"Int. J. Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1093\/humrep\/det353","article-title":"Distribution of decidual natural killer cells and macrophages in the neighbourhood of the trophoblast invasion front: A quantitative evaluation","volume":"29","author":"Helige","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1399-0039.2004.00170.x","article-title":"Human uterine leukocytes and pregnancy","volume":"63","author":"Trundley","year":"2004","journal-title":"Tissue Antigens"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.it.2017.01.009","article-title":"HLA-G: At the Interface of Maternal-Fetal Tolerance","volume":"38","author":"Ferreira","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1053\/j.gastro.2018.07.019","article-title":"Interactions Between KIR3DS1 and HLA-F Activate Natural Killer Cells to Control HCV Replication in Cell Culture","volume":"155","author":"Lunemann","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1365-2567.2008.03019.x","article-title":"Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies","volume":"127","author":"Apps","year":"2009","journal-title":"Immunology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.3201\/eid1211.060152","article-title":"Emerging infections and pregnancy","volume":"12","author":"Jamieson","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/pd.5446","article-title":"Zika virus during pregnancy: From maternal exposure to congenital Zika virus syndrome","volume":"39","author":"Pomar","year":"2019","journal-title":"Prenat. Diagn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/cid\/ciy318","article-title":"Seroprevalence of Herpes Simplex Virus Types 1 and 2 Among Pregnant Women and Sexually Active, Nonpregnant Women in the United States","volume":"67","author":"Patton","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJM199708213370801","article-title":"The acquisition of herpes simplex virus during pregnancy","volume":"337","author":"Brown","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika virus. I. Isolations and serological specificity","volume":"46","author":"Dick","year":"1952","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"A1","DOI":"10.1016\/j.placenta.2016.03.008","article-title":"Editorial: ZIKA virus and placenta","volume":"40","author":"Sadovsky","year":"2016","journal-title":"Placenta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.chom.2016.05.004","article-title":"An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors","volume":"19","author":"Shan","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18","DOI":"10.5858\/arpa.2016-0429-ED","article-title":"The Origins and Emergence of Zika Virus, the Newest TORCH Infection: What\u2019s Old Is New Again","volume":"141","author":"Schwartz","year":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"4864","DOI":"10.1128\/JVI.00252-16","article-title":"Zika Virus: New Clinical Syndromes and Its Emergence in the Western Hemisphere","volume":"90","author":"Lazear","year":"2016","journal-title":"J. Virol."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/aji.12501","article-title":"Type I Interferon Regulates the Placental Inflammatory Response to Bacteria and is Targeted by Virus: Mechanism of Polymicrobial Infection-Induced Preterm Birth","volume":"75","author":"Racicot","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.virusres.2012.05.010","article-title":"HSV-2 inhibits type-I interferon signaling via multiple complementary and compensatory STAT2-associated mechanisms","volume":"167","author":"Kadeppagari","year":"2012","journal-title":"Virus Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1038\/s41423-018-0050-y","article-title":"Relevance of placental type I interferon beta regulation for pregnancy success","volume":"15","author":"Kwon","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.4049\/jimmunol.2300081","article-title":"Twist1-IRF9 Interaction Is Necessary for IFN-Stimulated Gene Anti-Zika Viral Infection","volume":"210","author":"You","year":"2023","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1600-0897.2010.00817.x","article-title":"Viral ssRNA induces first trimester trophoblast apoptosis through an inflammatory mechanism","volume":"64","author":"Aldo","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e52450","DOI":"10.15252\/embr.202152450","article-title":"Placenta-derived interferon-stimulated gene 20 controls ZIKA virus infection","volume":"22","author":"Ding","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1600-0897.2010.00880.x","article-title":"Trophoblast-derived exosomes mediate monocyte recruitment and differentiation","volume":"65","author":"Atay","year":"2011","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1016\/j.placenta.2013.11.002","article-title":"Review: Placenta-specific microRNAs in exosomes-good things come in nano-packages","volume":"35","author":"Ouyang","year":"2014","journal-title":"Placenta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.4049\/jimmunol.1300081","article-title":"HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors","volume":"191","author":"Goodridge","year":"2013","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1002\/1521-4141(200012)30:12<3552::AID-IMMU3552>3.0.CO;2-L","article-title":"Functional characterization of HLA-F and binding of HLA-F tetramers to ILT2 and ILT4 receptors","volume":"30","author":"Lepin","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.immuni.2017.06.002","article-title":"Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors","volume":"46","author":"Dulberger","year":"2017","journal-title":"Immunity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.immuni.2017.06.004","article-title":"HLA-F: A New Kid Licensed for Peptide Presentation","volume":"46","author":"Sim","year":"2017","journal-title":"Immunity"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Luo, F., Liu, F., Guo, Y., Xu, W., Li, Y., Yi, J., Fournier, T., Degrelle, S., Zitouni, H., and Hernandez, I. (2023). Single-cell profiling reveals immune disturbances landscape and HLA-F-mediated immune tolerance at the maternal-fetal interface in preeclampsia. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1234577"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"641.e1","DOI":"10.1016\/j.ajog.2022.07.021","article-title":"Human leukocyte antigen HLA-C, HLA-G, HLA-F, and HLA-E placental profiles are altered in early severe preeclampsia and preterm birth with chorioamnionitis","volume":"227","author":"Dunk","year":"2022","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s10020-025-01201-w","article-title":"HLA-F regulates the proliferation of trophoblast via PKM2-dependent glycolysis in the pathogenesis of preeclampsia","volume":"31","author":"Xu","year":"2025","journal-title":"Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/aji.12578","article-title":"HSV-2 enhances ZIKV infection of the placenta and induces apoptosis in first-trimester trophoblast cells","volume":"76","author":"Aldo","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1600-0897.2012.01116.x","article-title":"Th17 and regulatory T cells in women with recurrent pregnancy loss","volume":"67","author":"Lee","year":"2012","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.placenta.2009.08.007","article-title":"The isolation and characterization of a novel telomerase immortalized first trimester trophoblast cell line, Swan 71","volume":"30","author":"Abrahams","year":"2009","journal-title":"Placenta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1002\/ijc.28845","article-title":"In vivo evidence that secretion of HLA-G by immunogenic tumor cells allows their evasion from immunosurveillance","volume":"135","author":"Loumagne","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1447-0756.2008.00963.x","article-title":"Toll-like receptors and pregnancy: Trophoblast as modulators of the immune response","volume":"35","author":"Koga","year":"2009","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1093\/humrep\/del178","article-title":"Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I: C)","volume":"21","author":"Abrahams","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.stem.2016.04.014","article-title":"Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3","volume":"19","author":"Dang","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1016\/S0140-6736(16)00650-4","article-title":"Teratogenic effects of the Zika virus and the role of the placenta","volume":"387","author":"Adibi","year":"2016","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.4049\/jimmunol.1401538","article-title":"HSV-2 immediate-early protein US1 inhibits IFN-beta production by suppressing association of IRF-3 with IFN-beta promoter","volume":"194","author":"Zhang","year":"2015","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jcv.2018.04.016","article-title":"The risk of herpes simplex virus and human cytomegalovirus infection during pregnancy upon adverse pregnancy outcomes: A meta-analysis","volume":"104","author":"Shi","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/pd.5587","article-title":"Fetal and neonatal abnormalities due to congenital herpes simplex virus infection: A literature review","volume":"40","author":"Fa","year":"2020","journal-title":"Prenat. Diagn."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Felker, A.M., Nguyen, P., and Kaushic, C. (2021). Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model. Viruses, 13.","DOI":"10.3390\/v13101929"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e00785-17","DOI":"10.1128\/JVI.00785-17","article-title":"Zika Virus Escapes NK Cell Detection by Upregulating Major Histocompatibility Complex Class I Molecules","volume":"91","author":"Glasner","year":"2017","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7666","DOI":"10.1128\/JVI.02274-07","article-title":"Dengue virus replicon expressing the nonstructural proteins suffices to enhance membrane expression of HLA class I and inhibit lysis by human NK cells","volume":"82","author":"Hershkovitz","year":"2008","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5663","DOI":"10.1128\/JVI.75.12.5663-5671.2001","article-title":"Modulation of transporter associated with antigen processing (TAP)-mediated peptide import into the endoplasmic reticulum by flavivirus infection","volume":"75","author":"Momburg","year":"2001","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1600-065X.1996.tb00908.x","article-title":"Flavivirus-induced up-regulation of MHC class I antigens; implications for the induction of CD8+ T-cell-mediated autoimmunity","volume":"152","author":"Lobigs","year":"1996","journal-title":"Immunol. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Guan, X., Zhang, M., Fu, M., Luo, S., and Hu, Q. (2019). Herpes Simplex Virus Type 2 Immediate Early Protein ICP27 Inhibits IFN-\u03b2 Production in Mucosal Epithelial Cells by Antagonizing IRF3 Activation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00290"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Yang, Y., Wang, W., Weng, J., Li, H., Ma, Y., Liu, L., and Ma, W. (2022). Advances in the study of HLA class Ib in maternal-fetal immune tolerance. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.976289"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e70293","DOI":"10.1111\/tan.70293","article-title":"Investigations of HLA-F and HLA-G 3\u2032UTR Polymorphisms in Preeclampsia and Fetal Growth Restriction Indicate a Possible Role of HLA-F-HLA-G Haplotypes and Diplotypes","volume":"106","author":"Christiansen","year":"2025","journal-title":"HLA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/jvh.12395","article-title":"Association of an HLA-G 14-bp Insertion\/Deletion polymorphism with high HBV replication in chronic hepatitis","volume":"22","author":"Laaribi","year":"2015","journal-title":"J. Viral Hepat."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/s41577-025-01191-0","article-title":"Innate immune responses to pathogens at the maternal\u2013fetal interface","volume":"25","author":"Alippe","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e12643","DOI":"10.1111\/aji.12643","article-title":"Definitive class I human leukocyte antigen expression in gestational placentation: HLA-F, HLA-E, HLA-C, and HLA-G in extravillous trophoblast invasion on placentation, pregnancy, and parturition","volume":"77","author":"Hackmon","year":"2017","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.4049\/jimmunol.171.3.1376","article-title":"Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition","volume":"171","author":"Ishitani","year":"2003","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Zhang, X., and Wei, H. (2021). Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.728291"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/aji.12355","article-title":"Viral infections during pregnancy","volume":"73","author":"Silasi","year":"2015","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e79794","DOI":"10.7554\/eLife.79794","article-title":"Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface","volume":"11","author":"Yang","year":"2022","journal-title":"eLife"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Woon, E.V., Nikolaou, D., MacLaran, K., Norman-Taylor, J., Bhagwat, P., Cuff, A.O., Johnson, M.R., and Male, V. (2022). Uterine NK cells underexpress KIR2DL1\/S1 and LILRB1 in reproductive failure. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1108163"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1089\/thy.1999.9.643","article-title":"The immunology of pregnancy","volume":"9","author":"Weetman","year":"1999","journal-title":"Thyroid"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"103764","DOI":"10.1016\/j.jri.2022.103764","article-title":"Leukocyte immunoglobulin-like receptor subfamily B: A novel immune checkpoint molecule at the maternal-fetal interface","volume":"155","author":"Wang","year":"2022","journal-title":"J. Reprod. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4997\/jrcpe.2016.102","article-title":"Zika virus, emergencies, uncertainty and vulnerable populations","volume":"46","author":"Roth","year":"2016","journal-title":"J. R. Coll. Physicians Edinb."},{"key":"ref_75","first-page":"331","article-title":"Zika Virus Infection in Pregnant Women in Rio de Janeiro-Preliminary Report","volume":"71","author":"Brasil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"26","DOI":"10.5858\/arpa.2016-0382-RA","article-title":"Zika Virus Infection in Pregnancy, Microcephaly, and Maternal and Fetal Health: What We Think, What We Know, and What We Think We Know","volume":"141","author":"Alvarado","year":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/nrmicro.2016.125","article-title":"Zika virus-reigniting the TORCH","volume":"14","author":"Coyne","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"eaao1680","DOI":"10.1126\/sciimmunol.aao1680","article-title":"Type I interferons instigate fetal demise after Zika virus infection","volume":"3","author":"Yockey","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_79","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_80","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"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/6\/603\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:27:51Z","timestamp":1779942471000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/6\/603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":80,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["v18060603"],"URL":"https:\/\/doi.org\/10.3390\/v18060603","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]}}}