{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T09:38:23Z","timestamp":1758274703928,"version":"3.41.2"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7254380"],"award-info":[{"award-number":["7254380"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatitis E virus (HEV)-associated renal injury is mainly reported in immunocompromised patients. Here we investigated HEV-associated renal injury in non-immunocompromised acute hepatitis E (AHE) patients and rabbits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 35 non-immunocompromised AHE patients were tested for kidney function parameters and HEV markers. HEV3- and HEV4-infected rabbits were tested for alanine aminotransferase, creatinine (Cr), and HEV markers. HEV-associated renal injury and renal HEV replication were analyzed by histopathology and RT-qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The non-immunocompromised AHE patients all showed normal serum Cr, blood urea nitrogen (BUN), and urine acid (UA). However, 25% of non-immunocompromised AHE patients showed proteinuria. In the rabbit model, HEV replication was observed in kidney tissues. The HEV-infected rabbits showed a transient elevated Cr level. Renal injury, including focal lymphocytic infiltration and tubular protein casts, was observed in rabbits across acute, recovery, and chronic phases of HEV infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Proteinuria is not uncommon in non-immunocompromised AHE patients, indicating that HEV infection affects the kidney. We further proved that HEV can cause renal injury in a rabbit model.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1583006","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T05:27:08Z","timestamp":1746509228000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatitis E virus infection and renal injury in non-immunocompromised host: clinical investigation and rabbit model study"],"prefix":"10.3389","volume":"15","author":[{"given":"Weigang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiyu","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanyun","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunjie","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"70","DOI":"10.4103\/0971-4065.34822","article-title":"Hepatitis E associated immune thrombocytopenia and membranous glomerulonephritis","volume":"2","author":"Ali","year":"2001","journal-title":"Indian J. Nephrol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1056\/NEJMc0903778","article-title":"Persistent carriage of hepatitis E virus in patients with HIV infection","volume":"361","author":"Dalton","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1111\/tid.12353","article-title":"Successful treatment of hepatitis E virus-associated cryoglobulinemic membranoproliferative glomerulonephritis with ribavirin","volume":"17","author":"Del","year":"2015","journal-title":"Transpl. Infect. Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1016\/j.jhep.2018.03.005","article-title":"EASL Clinical Practice Guidelines on hepatitis E virus infection","volume":"68","year":"2018","journal-title":"J. Hepatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1093\/infdis\/jiy128","article-title":"Pathological cerebrospinal fluid findings in patients with neuralgic amyotrophy and acute hepatitis E virus infection","volume":"217","author":"Fritz","year":"2018","journal-title":"J. Infect. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jhep.2015.08.034","article-title":"Detection and assessment of infectivity of hepatitis E virus in urine","volume":"64","author":"Geng","year":"2016","journal-title":"J. Hepatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1056\/NEJMc0708687","article-title":"Chronic hepatitis E with cirrhosis in a kidney-transplant recipient","volume":"358","author":"Gerolami","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1053\/j.ajkd.2015.10.022","article-title":"Hepatitis E virus-induced cryoglobulinemic glomerulonephritis in a nonimmunocompromised person","volume":"67","author":"Guinault","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1002\/hep.32455","article-title":"Immunocompromised rabbit model of chronic HEV reveals liver fibrosis and distinct efficacy of different vaccination strategies","volume":"76","author":"He","year":"2022","journal-title":"Hepatology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e84624","DOI":"10.1128\/jvi.00846-24","article-title":"Optimization of immunosuppression strategies for the establishment of chronic hepatitis E virus infection in rabbits","volume":"98","author":"He","year":"2024","journal-title":"J. Virol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1056\/NEJMoa0706992","article-title":"Hepatitis E virus and chronic hepatitis in organ-transplant recipients","volume":"358","author":"Kamar","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1111\/j.1600-6143.2008.02286.x","article-title":"Hepatitis E virus-related cirrhosis in kidney- and kidney-pancreas-transplant recipients","volume":"8","author":"Kamar","year":"2008","journal-title":"Am. J. Transplant."},{"key":"B13","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1097\/TP.0b013e318245f14c","article-title":"Hepatitis E virus and the kidney in solid-organ transplant patients","volume":"93","author":"Kamar","year":"2012","journal-title":"Transplantation"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1056\/NEJMoa1215246","article-title":"Ribavirin for chronic hepatitis E virus infection in transplant recipients","volume":"370","author":"Kamar","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"17086","DOI":"10.1038\/nrdp.2017.86","article-title":"Hepatitis E virus infection","volume":"3","author":"Kamar","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B16","doi-asserted-by":"publisher","first-page":"8849","DOI":"10.1038\/s41467-024-53072-0","article-title":"HEV ORF2 protein-antibody complex deposits are associated with glomerulonephritis in hepatitis E with reduced immune status","volume":"15","author":"Leblond","year":"2024","journal-title":"Nat. Commun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1080\/22221751.2019.1643260","article-title":"Hepatitis E-related adverse pregnancy outcomes and their prevention by hepatitis E vaccine in a rabbit model","volume":"8","author":"Li","year":"2019","journal-title":"Emerg. Microbes. Infect."},{"key":"B18","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1053\/j.gastro.2024.03.038","article-title":"An immunocompetent Mongolian gerbil model for hepatitis E virus genotype \u20131 infection","volume":"167","author":"Liu","year":"2024","journal-title":"Gastroenterology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1136\/gutjnl-2024-332784","article-title":"Establishment of enterically transmitted hepatitis virus animal models using lipid nanoparticle-based full-length viral genome RNA delivery system","volume":"74","author":"Liu","year":"2025","journal-title":"Gut"},{"key":"B20","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.jinf.2019.01.004","article-title":"Hepatitis E virus genotype 3 and capsid protein in the blood and urine of immunocompromised patients","volume":"78","author":"Marion","year":"2019","journal-title":"J. Infect."},{"key":"B21","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/nrgastro.2017.150","article-title":"Hepatitis E virus: advances and challenges","volume":"15","author":"Nimgaonkar","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"7544","DOI":"10.3748\/wjg.v20.i24.7544","article-title":"Hepatitis C virus associated glomerulopathies","volume":"20","author":"Ozkok","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1016\/j.jhep.2016.11.016","article-title":"Hepatitis E virus: Infection beyond the liver","volume":"66","author":"Pischke","year":"2017","journal-title":"J. Hepatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41581-018-0081-8","article-title":"Hepatitis C virus and the kidney","volume":"15","author":"Pol","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.virusres.2015.12.012","article-title":"Antigen detection and apoptosis in Mongolian gerbil\u2019s kidney experimentally intraperitoneally infected by swine hepatitis E virus","volume":"213","author":"Soomro","year":"2016","journal-title":"Virus Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"E211","DOI":"10.1111\/tid.2013.15.issue-6","article-title":"Hepatitis E virus infection as a new probable cause of de novo membranous nephropathy after kidney transplantation","volume":"15","author":"Taton","year":"2013","journal-title":"Transpl. Infect. Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.jhep.2019.04.022","article-title":"The burden of hepatitis E among patients with haematological Malignancies: A retrospective European cohort study","volume":"71","author":"von Felden","year":"2019","journal-title":"J. Hepatol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.jinf.2016.06.005","article-title":"Clinical and virological profiling of sporadic hepatitis E virus infection in China","volume":"73","author":"Wang","year":"2016","journal-title":"J. Infect."},{"key":"B29","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1136\/gutjnl-2016-312023","article-title":"Experimental infection of rabbits with genotype 3 hepatitis E virus produced both chronicity and kidney injury","volume":"66","author":"Wang","year":"2017","journal-title":"Gut"},{"key":"B30","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1080\/22221751.2020.1761762","article-title":"Presence and persistence of hepatitis E virus RNA and proteins in human bone marrow","volume":"9","author":"Wang","year":"2020","journal-title":"Emerg. Microbes. Infect."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3040","DOI":"10.1128\/JCM.39.9.3040-3046.2001","article-title":"Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model","volume":"39","author":"Williams","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2791","DOI":"10.1007\/s00705-015-2574-0","article-title":"Swine and rabbits are the main reservoirs of hepatitis E virus in China: detection of HEV RNA in feces of farmed and wild animals","volume":"160","author":"Xia","year":"2015","journal-title":"Arch. Virol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1002\/hep.32745","article-title":"Urine is a viral antigen reservoir in hepatitis E virus infection","volume":"77","author":"Ying","year":"2022","journal-title":"Hepatology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"4922","DOI":"10.1016\/j.vaccine.2015.07.040","article-title":"Hepatitis E vaccine immunization for rabbits to prevent animal HEV infection and zoonotic transmission","volume":"33","author":"Zhang","year":"2015","journal-title":"Vaccine"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1583006\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T05:27:09Z","timestamp":1746509229000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1583006\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":34,"alternative-id":["10.3389\/fcimb.2025.1583006"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1583006","relation":{},"ISSN":["2235-2988"],"issn-type":[{"type":"electronic","value":"2235-2988"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"article-number":"1583006"}}