{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:05:14Z","timestamp":1784952314494,"version":"3.55.0"},"reference-count":58,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Interferon &amp; Cytokine Research"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p>\n                    Distinct transcriptional isoforms of the interferon lambda receptor 1 (\n                    <jats:italic toggle=\"yes\">IFNLR1<\/jats:italic>\n                    ) are expressed in hepatocytes, but whether corresponding full-length and truncated IFNLR1 protein variants have discrete function is unclear. We quantitated\n                    <jats:italic toggle=\"yes\">IFNLR1<\/jats:italic>\n                    isoforms in liver and blood from individuals with chronic hepatitis C virus (HCV) infection before and after antiviral treatment, hypothesizing their relative expression may differentially change during resolution of virus-induced inflammation. We also expressed FLAG-tagged IFNLR1 variants in stem cell-derived hepatocytes (iHeps) with abrogated endogenous\n                    <jats:italic toggle=\"yes\">IFNLR1<\/jats:italic>\n                    to evaluate their function.\n                    <jats:italic toggle=\"yes\">IFNLR1<\/jats:italic>\n                    isoforms decreased in liver and blood during treatment of HCV, but no distinct pattern of decline was observed for any individual isoform. Expression of full-length IFNLR1 enabled lambda interferon (IFNL)-induced expression of antiviral and proinflammatory genes and augmented inhibition of hepatitis B virus (HBV) replication relative to wild-type (WT) iHeps. A noncanonical IFNLR1 variant missing part of the JAK1 binding domain enabled IFNLs to induce antiviral genes but could not support induction of proinflammatory genes or augmented HBV inhibition beyond that observed in WT iHeps with intact endogenous\n                    <jats:italic toggle=\"yes\">IFNLR1<\/jats:italic>\n                    . A secreted IFNLR1 variant had no identified function in iHeps lacking endogenous\n                    <jats:italic toggle=\"yes\">IFNLR1<\/jats:italic>\n                    . Although relative expression of individual\n                    <jats:italic toggle=\"yes\">IFNLR1<\/jats:italic>\n                    isoforms did not distinctly change during HCV treatment, functional studies in iHeps suggest IFNLR1 variants could function to titrate antiviral versus proinflammatory responses in hepatocytes in the context of viral hepatitis.\n                  <\/jats:p>","DOI":"10.1089\/jir.2024.0262","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T19:19:31Z","timestamp":1739215171000},"page":"174-183","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Function of Interferon Lambda Receptor 1 Variants in Stem Cell-Derived Hepatocytes with Abrogated Endogenous\n                    <i>IFNLR1<\/i>"],"prefix":"10.1177","volume":"45","author":[{"given":"Laura A.","family":"Novotny","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana S.","family":"Kappler","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5240-7115","authenticated-orcid":false,"given":"Eric G.","family":"Meissner","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA."},{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, South Carolina, 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