{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:34:37Z","timestamp":1772555677197,"version":"3.50.1"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T00:00:00Z","timestamp":1641600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T00:00:00Z","timestamp":1641600000000},"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":["Hepatology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>CD8 T cells are essential in controlling HBV infection. Viral control is dependent on efficient recognition of HBV\u2010infected hepatocytes by CD8 T cells, which can induce direct lysis of infected hepatocytes. In addition, CD8 T cells produce interferon (IFN)\u2010\u03b3, which mediates noncytopathic viral clearance. Innate immunomodulators and HBV\u2010targeted RNA interference (RNAi) are being developed to treat chronic hepatitis B (CHB), but may modify HBV antigen presentation and impact CD8 T\u2010cell recognition, in addition to their primary mechanisms of action.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>HBV\u2010infected HepG2\u2010NTCP cells were treated with tenofovir disoproxil fumarate (TDF), Toll\u2010like receptor (TLR) 7\/8 agonists, TLR7\/8 conditioned media (CM) collected from immune cells, or RNAi using short interfering RNAs. The effect of these treatments on antigen presentation was measured through coculture with CD8 T cells recognizing human leukocyte antigen\u2013A0201 restricted epitopes, HBc18\u201027 or HBs183\u2010191. Cytokine profiles of TLR7\/8 CM were measured using a cytometric bead array. TDF reduced viral replication, but not CD8 T\u2010cell recognition, of infected cells. Direct exposure of infected HepG2\u2010NTCP to TLR7\/8 agonists had no impact on T\u2010cell recognition. Exposure of infected HepG2\u2010NTCP to TLR7\/8 CM enhanced HBV\u2010specific CD8 T\u2010cell recognition through type 1 interferon (IFN) and IFN\u2010\u03b3\u2010dependent mechanisms. RNAi rapidly suppressed HBV\u2010DNA, HBcAg, and HBsAg expression, impairing recognition by HBV\u2010specific CD8 T cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Immunomodulation and RNAi, but not nucleos(t)ide analogues, alter the recognition of infected HepG2\u2010NTCP by HBV\u2010specific CD8 T cells. Understanding these changes will inform combination treatments for CHB.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32230","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T09:00:14Z","timestamp":1636275614000},"page":"1539-1550","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":11,"title":["Immunomodulation and RNA interference alter hepatitis B virus\u2013specific CD8 T\u2010cell recognition of infected HepG2\u2010NTCP"],"prefix":"10.1097","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4790-2234","authenticated-orcid":false,"given":"Adrian","family":"Kuipery","sequence":"first","affiliation":[{"name":"Department of Immunology,University of Toronto,Toronto,Ontario,Canada"},{"name":"Toronto Center for Liver Disease,Toronto General Hospital Research Institute,University Health Network,Toronto,Ontario,Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Diego","family":"Sanchez Vasquez","sequence":"additional","affiliation":[{"name":"Department of Immunology,University of Toronto,Toronto,Ontario,Canada"},{"name":"Toronto Center for Liver Disease,Toronto General Hospital Research Institute,University Health Network,Toronto,Ontario,Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aman","family":"Mehrotra","sequence":"additional","affiliation":[{"name":"Toronto Center for Liver Disease,Toronto General Hospital Research Institute,University Health Network,Toronto,Ontario,Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan J.","family":"Feld","sequence":"additional","affiliation":[{"name":"Toronto Center for Liver Disease,Toronto General Hospital Research Institute,University Health Network,Toronto,Ontario,Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry L. 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