{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:01:05Z","timestamp":1785416465564,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center Val de Loire Region","award":["2019-00134917"],"award-info":[{"award-number":["2019-00134917"]}]},{"name":"Center Val de Loire Region","award":["2019-1850"],"award-info":[{"award-number":["2019-1850"]}]},{"award":["2019-00134917"],"award-info":[{"award-number":["2019-00134917"]}],"id":[{"id":"https:\/\/ror.org\/02wwzvj46","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2019-1850"],"award-info":[{"award-number":["2019-1850"]}],"id":[{"id":"https:\/\/ror.org\/02wwzvj46","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003323","name":"ANRS","doi-asserted-by":"crossref","award":["call 2023-1"],"award-info":[{"award-number":["call 2023-1"]}],"id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003323","name":"ANRS","doi-asserted-by":"crossref","award":["ANRS0374"],"award-info":[{"award-number":["ANRS0374"]}],"id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"crossref"}]},{"award":["call 2023-1"],"award-info":[{"award-number":["call 2023-1"]}],"id":[{"id":"https:\/\/ror.org\/01kv58h76","id-type":"ROR","asserted-by":"publisher"}]},{"award":["ANRS0374"],"award-info":[{"award-number":["ANRS0374"]}],"id":[{"id":"https:\/\/ror.org\/01kv58h76","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007526","name":"University of Tours","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007526","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02wwzvj46","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hepatitis E virus (HEV) is a zoonotic cause of acute viral hepatitis that can become chronic in immunocompromised patients. Recently, host microRNAs (miRNAs) miR-122-5p, miR-125b-5p, miR-99a-5p, and miR-192-5p have been associated with acute HEV infection and with chronic HEV infection. Yet, the expression levels of miRNAs during the early phase of HEV infection remained unexplored. In this context, we aimed to identify changes in miRNA profiles occurring between the diagnosis of HEV infection and HEV cure in immunocompromised patients and in a pig model. We retrospectively included 9 immunocompromised patients with HEV infection (5 chronic and 4 resolutive) and 10 immunocompromised pigs (6 HEV-infected and 4 controls). RNAseq was retrospectively performed on pig samples. MiRNA expression was quantified by qPCR on pig and human samples.: Small RNA sequencing and targeted qPCR analyses revealed a pronounced, stage-dependent remodeling of miRNA expression during HEV infection. In patients, viral clearance was associated with early upregulation of miR-99a-5p, miR-122-5p, miR-125b-5p, and miR-194-5p, whereas progression to chronic infection was characterized by sustained downregulation of miR-23a-3p, miR-27a-3p, miR-106a-5p, miR-221-3p, and miR-223-3p. Likewise, a correlation was observed between the dysregulation of miR-181a-5p, miR-425-5p, and let-7b-5p with viral load (HEV RNA), while miR-27a-3p and miR-106a-5p were associated with ALT levels. In pigs, miR-122-5p was upregulated 10 weeks p.i., while 10 miRNAs (miR-16, miR-20a-5p, miR-23a-3p, miR-27a, miR-29a-3p, miR-140-5p, miR-181a, miR-191, miR-423-5p, and miR-99a-5p) were downregulated 11 weeks p.i. MiR-23a-3p, miR-27a, miR-99a-5p, miR-181a, and miR-425-5p were associated with HEV infection in both humans and pigs. Persistent HEV infection in immunocompromised patients and in a pig model showed partial overlap in miRNA responses. Our findings identified circulating miRNAs as stage-specific molecular markers of HEV infection in immunocompromised hosts. MiRNAs could contribute to early stratification of high-risk patients, improving outcomes for vulnerable patients facing this emerging viral disease.<\/jats:p>","DOI":"10.3390\/biom16060799","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:08:02Z","timestamp":1780535282000},"page":"799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Follow-Up of microRNA Expression During Hepatitis E Virus Infection in Immunocompromised Hosts"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3214-1265","authenticated-orcid":false,"given":"Nancy","family":"Le\u00f3n-Janampa","sequence":"first","affiliation":[{"name":"INSERM U1259 MAVIVHe, Tours University and Tours University Hospital, 37000 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denys","family":"Brand","sequence":"additional","affiliation":[{"name":"INSERM U1259 MAVIVHe, Tours University and Tours University Hospital, 37000 Tours, France"},{"name":"Department of Bacteriology-Virology-Hygiene, Tours University Hospital, 37044 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-8703","authenticated-orcid":false,"given":"Julien","family":"Marlet","sequence":"additional","affiliation":[{"name":"INSERM U1259 MAVIVHe, Tours University and Tours University Hospital, 37000 Tours, France"},{"name":"Department of Bacteriology-Virology-Hygiene, Tours University Hospital, 37044 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e04664-22","DOI":"10.1128\/spectrum.04664-22","article-title":"Specific Plasma MicroRNA Signatures Underlying the Clinical Outcomes of Hepatitis E Virus Infection","volume":"11","author":"Costafreda","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5337","DOI":"10.1038\/s41598-020-62159-9","article-title":"Specific circulating microRNAs during hepatitis E infection can serve as indicator for chronic hepatitis E","volume":"10","author":"Harms","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1007\/s10096-025-05207-4","article-title":"Differential miRNA signatures in Hepatitis E Virus Infection: Insights into acute, chronic, and pregnancy-related outcomes","volume":"44","author":"Marlet","year":"2025","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e01999-17","DOI":"10.1128\/JVI.01999-17","article-title":"Positive Regulation of Hepatitis E Virus Replication by MicroRNA-122","volume":"92","author":"Haldipur","year":"2018","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5322","DOI":"10.1016\/j.jmb.2020.07.015","article-title":"Uncovering the Roles of miR-214 in Hepatitis E Virus Replication","volume":"432","author":"Patil","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_6","first-page":"e0274","article-title":"A pig model of chronic hepatitis E displaying persistent viremia and a downregulation of innate immune responses in the liver","volume":"7","author":"Barc","year":"2023","journal-title":"Hepatol. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105382","DOI":"10.1016\/j.phrs.2020.105382","article-title":"Multiple microRNAs regulate tacrolimus metabolism through CYP3A5","volume":"164","author":"Gu","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1097\/TP.0b013e31828618d8","article-title":"Plasma microRNA, a potential biomarker for acute rejection after liver transplantation","volume":"95","author":"Hu","year":"2013","journal-title":"Transplantation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.25122\/jml-2022-0181","article-title":"Relevant biomarkers of kidney allograft rejection","volume":"15","author":"Loga","year":"2022","journal-title":"J. Med. Life"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1111\/j.1600-6143.2009.02834.x","article-title":"Special Issue: KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients","volume":"9","author":"Eckardt","year":"2009","journal-title":"Am. J. Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1128\/JCM.05942-11","article-title":"Genotype 3 Diversity and Quantification of Hepatitis E Virus RNA","volume":"50","author":"Abravanel","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6914","DOI":"10.1073\/pnas.1705446114","article-title":"Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity","volume":"114","author":"Cao","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.ekir.2024.01.054","article-title":"Relevance of Tacrolimus Trough Concentration and Hepatitis E virus Genetic Changes in Kidney Transplant Recipients with Chronic Hepatitis E","volume":"9","author":"Boennec","year":"2024","journal-title":"Kidney Int. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/j.jhep.2018.03.005","article-title":"EASL Clinical Practice Guidelines on hepatitis E virus infection","volume":"68","author":"Dalton","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.jinf.2014.10.017","article-title":"Differences in serum microRNA profiles in hepatitis B and C virus infection","volume":"70","author":"Akamatsu","year":"2015","journal-title":"J. Infect."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Barbu, M.G., Condrat, C.E., Thompson, D.C., Bugnar, O.L., Cretoiu, D., Toader, O.D., Suciu, N., and Voinea, S.C. (2020). MicroRNA Involvement in Signaling Pathways During Viral Infection. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00143"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Becker, P.P., Rau, M., Schmitt, J., Malsch, C., Hammer, C., Bantel, H., M\u00fcllhaupt, B., and Geier, A. (2015). Performance of Serum microRNAs -122, -192 and -21 as Biomarkers in Patients with Non-Alcoholic Steatohepatitis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142661"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4513","DOI":"10.1007\/s11033-014-3322-3","article-title":"Profiles of serum microRNAs; miR-125b-5p and miR223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinoma","volume":"41","author":"Giray","year":"2014","journal-title":"Mol. Biol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gupta, S., Singh, P., Tasneem, A., Almatroudi, A., Rahmani, A.H., Dohare, R., and Parveen, S. (2023). Integrative Multiomics and Regulatory Network Analyses Uncovers the Role of OAS3, TRAFD1, miR-222-3p, and miR-125b-5p in Hepatitis E Virus Infection. Genes, 14.","DOI":"10.3390\/genes14010042"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"McGowan, K., Simpson, K.J., and Petrik, J. (2020). Expression Profiles of Exosomal MicroRNAs from HEV- and HCV-Infected Blood Donors and Patients: A Pilot Study. Viruses, 12.","DOI":"10.3390\/v12080833"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.gendis.2015.01.001","article-title":"MicroRNAs: Role in Hepatitis C Virus pathogenesis","volume":"2","author":"Shrivastava","year":"2015","journal-title":"Genes Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lee, E.B., Sung, P.S., Kim, J.-H., Park, D.J., Hur, W., and Yoon, S.K. (2020). microRNA-99a Restricts Replication of Hepatitis C Virus by Targeting mTOR and de novo Lipogenesis. Viruses, 12.","DOI":"10.3390\/v12070696"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.omtn.2022.02.005","article-title":"miR-221\/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review","volume":"27","author":"Arbitrio","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Du, H., Cui, S., Li, Y., Yang, G., Wang, P., Fikrig, E., and You, F. (2018). MiR-221 negatively regulates innate anti-viral response. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200385"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11262-013-0912-4","article-title":"Identification of miR-221 and -222 as important regulators in genotype IV swine hepatitis E virus ORF3-expressing HEK 293 cells","volume":"47","author":"Cheng","year":"2013","journal-title":"Virus Genes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5270","DOI":"10.1128\/JVI.03022-12","article-title":"MicroRNA-27a regulates lipid metabolism and inhibits hepatitis C virus replication in human hepatoma cells","volume":"87","author":"Shirasaki","year":"2013","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Daneshpour, M., and Ghadimi-Daresajini, A. (2023). Overview of miR-106a Regulatory Roles: From Cancer to Aging. Bioengineering, 10.","DOI":"10.3390\/bioengineering10080892"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gu, J., Xu, H., Chen, Y., Li, N., and Hou, X. (2022). MiR-223 as a Regulator and Therapeutic Target in Liver Diseases. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.860661"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"178107","DOI":"10.1016\/j.ejphar.2025.178107","article-title":"MicroRNA-29a attenuates inflammation and fibrosis in an animal model of NASH through MCJ inhibition and hippo pathway regulation","volume":"1005","author":"Yang","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.2147\/IJGM.S478709","article-title":"Serum microRNA-181a Expression Level in Patients with Acute Liver Failure and Its Correlation with Prognosis","volume":"17","author":"Wang","year":"2024","journal-title":"Int. J. Gen. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/hep.26296","article-title":"Up-regulation of Circulating miR-20a is correlated with Hepatitis C Virus-Mediated Liver Disease Progression","volume":"58","author":"Shrivastava","year":"2013","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"168050","DOI":"10.1016\/j.jmb.2023.168050","article-title":"Unravelling the Tripartite Interactions Among Hepatitis E Virus RNA, miR-140 and hnRNP K","volume":"435","author":"Patil","year":"2023","journal-title":"J. Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"965185","DOI":"10.1155\/2015\/965185","article-title":"Serum\/Plasma MicroRNAs as Biomarkers for HBV-Related Hepatocellular Carcinoma in China","volume":"2015","author":"Yin","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10574","DOI":"10.1074\/jbc.M117.785592","article-title":"An HNF4\u03b1-microRNA-194\/192 signaling axis maintains hepatic cell function","volume":"292","author":"Morimoto","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/liv.12961","article-title":"Micro RNAs mir-106a, mir-122 and mir-197 are increased in severe acute viral hepatitis with coagulopathy","volume":"36","author":"Weseslindtner","year":"2016","journal-title":"Liver Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/s12967-025-06286-9","article-title":"MiR-451a attenuates hepatic steatosis and hepatitis C virus replication by targeting glycerol kinase","volume":"23","author":"Majumdar","year":"2025","journal-title":"J. Transl. Med."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/799\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:16:32Z","timestamp":1780546592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["biom16060799"],"URL":"https:\/\/doi.org\/10.3390\/biom16060799","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]}}}