{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:43:00Z","timestamp":1787013780706,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["1K01AA026864"],"award-info":[{"award-number":["1K01AA026864"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      Approximately 3.5% of the global population is chronically infected with Hepatitis B Virus (HBV), which puts them at high risk of end\u2010stage liver disease, with the risk of persistent infection potentiated by alcohol consumption. However, the mechanisms underlying the effects of alcohol on HBV persistence remain unclear. Here, we aimed to establish\n                      <jats:italic>in vivo<\/jats:italic>\n                      \/\n                      <jats:italic>ex vivo<\/jats:italic>\n                      evidence that alcohol suppresses HBV peptides\u2010major histocompatibility complex (MHC) class I antigen display on primary human hepatocytes (PHH), which diminishes the recognition and clearance of HBV\u2010infected hepatocytes by cytotoxic T\u2010lymphocytes (CTLs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used fumarylacetoacetate hydrolase (Fah)\u2010\/\u2010, Rag2\u2010\/\u2010, common cytokine receptor gamma chain knock\u2010out (FRG\u2010KO) humanized mice transplanted with human leukocyte antigen\u2010A2 (HLA\u2010A2)\u2010positive hepatocytes. The mice were HBV\u2010infected and fed control and alcohol diets. Isolated hepatocytes were exposed\n                      <jats:italic>ex vivo<\/jats:italic>\n                      to HBV 18\u201027\u2010HLA\u2010A2\u2010restricted CTLs to quantify cytotoxicity. For mechanistic studies, we measured proteasome activities, unfolded protein response (UPR), and endoplasmic reticulum (ER) stress in hepatocytes from HBV\u2010infected humanized mouse livers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Conclusions<\/jats:title>\n                    <jats:p>We found that alcohol feeding attenuated HBV core 18\u201027\u2010HLA\u2010A2 complex presentation on infected hepatocytes due to the suppression of proteasome function and ER stress induction, which diminished both the processing of HBV peptides and trafficking of HBV\u2010MHC class I complexes to the hepatocyte surface. This alcohol\u2010mediated decrease in MHC class I\u2010restricted antigen presentation of the CTL epitope on target hepatocytes reduced the CTL\u2010specific elimination of infected cells, potentially leading to HBV\u2010infection persistence, which promotes end\u2010stage liver disease outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.14740","type":"journal-article","created":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T03:01:50Z","timestamp":1636772510000},"page":"40-51","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Ethanol attenuates presentation of cytotoxic T\u2010lymphocyte epitopes on hepatocytes of HBV\u2010infected humanized mice"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2981-568X","authenticated-orcid":false,"given":"Murali","family":"Ganesan","sequence":"first","affiliation":[{"name":"Research Service Veterans Affairs 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