{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:12:11Z","timestamp":1793059931498,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Organ transplant recipients are at high risk of developing chronic infection when exposed to hepatitis E virus (HEV), which can rapidly progress to liver fibrosis and cirrhosis. Macrophages play a key role in the response to the infection and disease progression. However, the interactions amongst immunosuppressants, macrophages, the course of HEV infection and activation of inflammatory response remain unclear. In this study, we generated M0, M1 and M2 macrophages from the human THP\u20101 cell line. These macrophages were then infected with HEV and treated with different immunosuppressants. We visualised viral infection using laser confocal microscopy, and quantitatively analysed viral replication and inflammatory responses by bulk sequencing, RT\u2010qPCR, ELISA and Western blotting. We found that the M1 inflammatory macrophages exhibited the highest, while M2 macrophages had the lowest levels of viral RNA. Genome\u2010wide transcriptome analysis indicated that viral, inflammation and immunity\u2010related pathways were predominantly upregulated by HEV infection. Dexamethasone exerted potent inhibitory effects on inflammatory response in macrophages. Mycophenolic acid (MPA) demonstrated inhibitory effects on viral replication, IL\u20101\u03b2 and TNF\u2010\u03b1 expression, whereas mTOR inhibitors had the opposite effects, and tacrolimus showed no clear effect. In conclusion, immunosuppressants can differentially affect HEV replication and the subsequent inflammatory responses in macrophages.<\/jats:p>","DOI":"10.1111\/jvh.70118","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T11:08:00Z","timestamp":1765883280000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Differential Effects of Immunosuppressants on Hepatitis E Virus Replication and the Triggered Inflammatory Responses in Macrophages"],"prefix":"10.1111","volume":"33","author":[{"given":"Jiahua","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC\u2010University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC\u2010University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Surgery Erasmus MC Transplant Institute, University Medical Center Rotterdam  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick P. 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