Multiple Functions of Cellular FLIP Are Essential for Replication of Hepatitis B Virus
DC Field | Value | Language |
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dc.contributor.author | Lee, Ah Ram | - |
dc.contributor.author | Lim, Keo-Heun | - |
dc.contributor.author | Park, Eun-Sook | - |
dc.contributor.author | Kim, Doo Hyun | - |
dc.contributor.author | Park, Yong Kwang | - |
dc.contributor.author | Park, Soree | - |
dc.contributor.author | Kim, Dong-Sik | - |
dc.contributor.author | Shin, Gu-Choul | - |
dc.contributor.author | Kang, Hong Seok | - |
dc.contributor.author | Won, Juhee | - |
dc.contributor.author | Sim, Heewoo | - |
dc.contributor.author | Ha, Yea Na | - |
dc.contributor.author | Jae, Byeongjune | - |
dc.contributor.author | Choi, Seong Il | - |
dc.contributor.author | Kim, Kyun-Hwan | - |
dc.date.accessioned | 2021-09-02T07:54:34Z | - |
dc.date.available | 2021-09-02T07:54:34Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2018-08 | - |
dc.identifier.issn | 0022-538X | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/73815 | - |
dc.description.abstract | Hepatitis B virus (HBV) infection is a leading cause of liver diseases; however, the host factors which facilitate the replication and persistence of HBV are largely unidentified. Cellular FLICE inhibitory protein (c-FLIP) is a typical antiapoptotic protein. In many cases of liver diseases, the expression level of c-FLIP is altered, which affects the fate of hepatocytes. We previously found that c-FLIP and its cleaved form interact with HBV X protein (HBx), which is essential for HBV replication, and regulate diverse cellular signals. In this study, we investigated the role of endogenous c-FLIP in HBV replication and its underlying mechanisms. The knockdown of endogenous c-FLIP revealed that this protein regulates HBV replication through two different mechanisms. (i) c-FLIP interacts with HBx and protects it from ubiquitin-dependent degradation. The N-terminal DED1 domain of c-FLIP is required for HBx stabilization. (ii) c-FLIP regulates the expression or stability of hepatocyte nuclear factors (HNFs), which have critical roles in HBV transcription and maintenance of hepatocytes. c-FLIP regulates the stability of HNFs through physical interactions. We verified our findings in three HBV infection systems: HepG2-NTCP cells, differentiated HepaRG cells, and primary human hepatocytes. In conclusion, our results identify c-FLIP as an essential factor in HBV replication. c-FLIP regulates viral replication through its multiple effects on viral and host proteins that have critical roles in HBV replication. IMPORTANCE Although the chronic hepatitis B virus (HBV) infection still poses a major health concern, the host factors which are required for the replication of HBV are largely uncharacterized. Our studies identify cellular FLICE inhibitory protein (c-FLIP) as an essential factor in HBV replication. We found the dual roles of c-FLIP in regulation of HBV replication: c-FLIP interacts with HBx and enhances its stability and regulates the expression or stability of hepatocyte nuclear factors which are essential for transcription of HBV genome. Our findings may provide a new target for intervention in persistent HBV infection. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC MICROBIOLOGY | - |
dc.subject | C-FLIP | - |
dc.subject | X-PROTEIN | - |
dc.subject | MOLECULAR CHAPERONES | - |
dc.subject | INDUCED APOPTOSIS | - |
dc.subject | HBX PROTEIN | - |
dc.subject | HEPATOCYTE DIFFERENTIATION | - |
dc.subject | EPIGENETIC REGULATION | - |
dc.subject | IN-VITRO | - |
dc.subject | EXPRESSION | - |
dc.subject | RECEPTOR | - |
dc.title | Multiple Functions of Cellular FLIP Are Essential for Replication of Hepatitis B Virus | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Dong-Sik | - |
dc.identifier.doi | 10.1128/JVI.00339-18 | - |
dc.identifier.scopusid | 2-s2.0-85050819875 | - |
dc.identifier.wosid | 000440292200012 | - |
dc.identifier.bibliographicCitation | JOURNAL OF VIROLOGY, v.92, no.16 | - |
dc.relation.isPartOf | JOURNAL OF VIROLOGY | - |
dc.citation.title | JOURNAL OF VIROLOGY | - |
dc.citation.volume | 92 | - |
dc.citation.number | 16 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Virology | - |
dc.relation.journalWebOfScienceCategory | Virology | - |
dc.subject.keywordPlus | C-FLIP | - |
dc.subject.keywordPlus | X-PROTEIN | - |
dc.subject.keywordPlus | MOLECULAR CHAPERONES | - |
dc.subject.keywordPlus | INDUCED APOPTOSIS | - |
dc.subject.keywordPlus | HBX PROTEIN | - |
dc.subject.keywordPlus | HEPATOCYTE DIFFERENTIATION | - |
dc.subject.keywordPlus | EPIGENETIC REGULATION | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordAuthor | hepatitis B virus | - |
dc.subject.keywordAuthor | HBx | - |
dc.subject.keywordAuthor | c-FLIP | - |
dc.subject.keywordAuthor | hepatocyte nuclear factor | - |
dc.subject.keywordAuthor | transcriptional control | - |
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