{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:23:13Z","timestamp":1780572193762,"version":"3.54.1"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2011,5,2]],"date-time":"2011-05-02T00:00:00Z","timestamp":1304294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T00:00:00Z","timestamp":1306886400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:sec><jats:title\/><jats:p><jats:bold>Interferon alpha (IFN\u03b1) is widely used for the treatment of viral hepatitis but substantial toxicity hampers its clinical use. In this work, we aimed at improving the efficacy of IFN\u03b1 therapy by increasing the IFN\u03b1 half-life and providing liver tropism. We selected apolipoprotein A-I (ApoA-I) as the stabilizing and targeting moiety. We generated plasmids encoding IFN\u03b1, albumin bound to IFN\u03b1 (ALF), or IFN\u03b1 linked to ApoA-I (IA) and mice were treated either by hydrodynamic administration of the plasmids or by injection of the corresponding recombinant proteins or high-density lipoproteins containing IA. The plasma half-life of IA was intermediate between IFN\u03b1 and ALF. IA was targeted to the liver and induced higher hepatic expression of interferon-stimulated genes than IFN\u03b1 or even ALF. IA exhibits stronger in vivo antiviral activity than IFN\u03b1 and the hematologic cytopenic effects of IA are milder than those observed when using IFN\u03b1 or ALF. In contrast to IFN\u03b1, IA does not cause activation-dependent cell death of lymphocytes in vitro. Accordingly, in vivo studies showed that IA boosts T-cell immune responses more efficiently than IFN\u03b1 or ALF. The difference in immunostimulatory activity between IFN\u03b1 and IA disappears in scavenger receptor class B type I (SR-BI) knockout mice, suggesting that crosstalk between SR-BI and IFN\u03b1 receptor is essential for enhanced induction of cytotoxic T cells by IA.<\/jats:bold><\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p><jats:bold>Anchoring IFN\u03b1 to ApoA-I prolongs the half-life of IFN\u03b1 and promotes targeting to the liver. Importantly, the fusion protein shows increased immunostimulatory properties and lower hematological toxicity. (HEPATOLOGY 2011;)<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1002\/hep.24306","type":"journal-article","created":{"date-parts":[[2011,3,21]],"date-time":"2011-03-21T16:19:35Z","timestamp":1300724375000},"page":"1864-1873","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":40,"title":["Anchoring interferon alpha to apolipoprotein A-I reduces hematological toxicity while enhancing immunostimulatory 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