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HBx, as a multifunctional viral protein encoded by the hepatitis B virus (HBV), promotes HBV replication and greatly contributes to the development of HBV-associated hepatocellular carcinoma (HCC). HBx interacts with several host factors in order to regulate HBV replication and evolve carcinogenesis. The cellular FADD-like IL-1\u03b2-converting enzyme (FLICE)-like inhibitory protein (c-FLIP) is a major factor that functions in a variety of cellular pathways and specifically in apoptosis. It has been shown that the interaction between HBx and c-FLIP determines HBV fate. In this review, we provide a comprehensive and detailed overview of the interplay between c-FLIP and HBV in various environmental circumstances. We describe strategies adapted by HBV to establish its chronic infection. We also summarize the conventional roles of c-FLIP and highlight the functional outcome of the interaction between c-FLIP and HBV or other viruses in viral replication and the innate immune system.<\/jats:p>","DOI":"10.3390\/v14020373","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T20:35:28Z","timestamp":1644784528000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Interaction between the Hepatitis B Virus and Cellular FLIP Variants in Viral Replication and the Innate Immune System"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6075-3352","authenticated-orcid":false,"given":"Ah Ram","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Kwang","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Chronic Viral Diseases, Center for Emerging Virus Research, National Institute of Infectious Disease, National Institute of Health, Cheongju 28159, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2852-2084","authenticated-orcid":false,"given":"Mehrangiz","family":"Dezhbord","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5266-072X","authenticated-orcid":false,"given":"Kyun-Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1016\/S0140-6736(15)61412-X","article-title":"Estimations of worldwide prevalence of chronic hepatitis B virus infection: A systematic review of data published between 1965 and 2013","volume":"386","author":"Schweitzer","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1007\/s00018-010-0357-z","article-title":"Dengue virus life cycle: Viral and host factors modulating infectivity","volume":"67","author":"Wilschut","year":"2010","journal-title":"Cell Mol. 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