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The presence of viral proteins further exacerbates the methylation defects to disrupt multiple pathways that promote the pathogenesis of liver disease. This review is a compilation of presentations that linked the methylation reaction defects with proteasome inhibition, decreased antigen presentation, and impaired interferon (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>) signaling in the hepatocytes and dysregulated <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1 expression in macrophages. Two therapeutic modalities, betaine and <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\u2010adenosylmethionine, can correct methylation defects to attenuate many <jats:styled-content style=\"fixed-case\">EtOH<\/jats:styled-content>\u2010induced liver changes, as well as improve <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content> signaling pathways, thereby overcoming viral treatment resistance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1530-0277.2012.01840.x","type":"journal-article","created":{"date-parts":[[2012,5,11]],"date-time":"2012-05-11T15:16:11Z","timestamp":1336749371000},"page":"1-7","source":"Crossref","is-referenced-by-count":9,"title":["Impact of Altered Methylation in Cytokine Signaling and Proteasome Function in Alcohol and Viral\u2010Mediated Diseases"],"prefix":"10.1111","volume":"37","author":[{"given":"Kusum K.","family":"Kharbanda","sequence":"first","affiliation":[{"name":"Research Service Veterans Affairs Nebraska\u2010Western 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