{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T13:41:32Z","timestamp":1793972492356,"version":"4.8.0"},"reference-count":41,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","journal-of-hepatology.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Hepatology"],"published-print":{"date-parts":[[2023,1]]},"DOI":"10.1016\/j.jhep.2022.08.041","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:08:12Z","timestamp":1663805292000},"page":"78-89","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":39,"title":["Effect of variants in LGP2 on MDA5-mediated activation of interferon response and suppression of hepatitis D virus replication"],"prefix":"10.1016","volume":"78","author":[{"given":"Nadine","family":"Gillich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0013-3685","authenticated-orcid":false,"given":"Zhenfeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-6109","authenticated-orcid":false,"given":"Marco","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1560-8038","authenticated-orcid":false,"given":"Stephan","family":"Urban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5601-9307","authenticated-orcid":false,"given":"Ralf","family":"Bartenschlager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhep.2022.08.041_bib1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.cyto.2015.02.010","article-title":"LGP2 synergy with MDA5 in RLR-mediated RNA recognition and antiviral signaling","volume":"74","author":"Bruns","year":"2015","journal-title":"Cytokine"},{"key":"10.1016\/j.jhep.2022.08.041_bib2","doi-asserted-by":"crossref","first-page":"9000","DOI":"10.1074\/jbc.R117.788398","article-title":"Discrimination of cytosolic self and non-self RNA by RIG-I-like receptors","volume":"292","author":"Lassig","year":"2017","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jhep.2022.08.041_bib3","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.molcel.2014.07.003","article-title":"The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly","volume":"55","author":"Bruns","year":"2014","journal-title":"Mol Cell"},{"key":"10.1016\/j.jhep.2022.08.041_bib4","doi-asserted-by":"crossref","first-page":"11664","DOI":"10.1093\/nar\/gkaa935","article-title":"Viral RNA recognition by LGP2 and MDA5, and activation of signaling through step-by-step conformational changes","volume":"48","author":"Duic","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jhep.2022.08.041_bib5","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/hep.27344","article-title":"Polymorphisms in melanoma differentiation-associated gene 5 link protein function to clearance of hepatitis C virus","volume":"61","author":"Hoffmann","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.08.041_bib6","doi-asserted-by":"crossref","DOI":"10.1126\/science.abd4570","article-title":"Inborn errors of type I IFN immunity in patients with life-threatening COVID-19","volume":"370","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.jhep.2022.08.041_bib7","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1126\/science.abg5953","article-title":"Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus","volume":"373","author":"Chen","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.jhep.2022.08.041_bib8","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1093\/hmg\/ddr377","article-title":"The selective footprints of viral pressures at the human RIG-I-like receptor family","volume":"20","author":"Vasseur","year":"2011","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.jhep.2022.08.041_bib9","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/323508a0","article-title":"Structure, sequence and expression of the hepatitis delta (delta) viral genome","volume":"323","author":"Wang","year":"1986","journal-title":"Nature"},{"key":"10.1016\/j.jhep.2022.08.041_bib10","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1128\/jvi.63.5.1945-1950.1989","article-title":"Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen","volume":"63","author":"Kuo","year":"1989","journal-title":"J\u00a0Virol"},{"key":"10.1016\/j.jhep.2022.08.041_bib11","doi-asserted-by":"crossref","first-page":"8490","DOI":"10.1073\/pnas.88.19.8490","article-title":"The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus","volume":"88","author":"Chang","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jhep.2022.08.041_bib12","doi-asserted-by":"crossref","first-page":"7375","DOI":"10.1128\/JVI.74.16.7375-7380.2000","article-title":"The large delta antigen of hepatitis delta virus potently inhibits genomic but not antigenomic RNA synthesis: a mechanism enabling initiation of viral replication","volume":"74","author":"Modahl","year":"2000","journal-title":"J\u00a0Virol"},{"key":"10.1016\/j.jhep.2022.08.041_bib13","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1126\/science.1598578","article-title":"Identification of a prenylation site in delta virus large antigen","volume":"256","author":"Glenn","year":"1992","journal-title":"Science"},{"key":"10.1016\/j.jhep.2022.08.041_bib14","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.00049","article-title":"Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus","volume":"1","author":"Yan","year":"2012","journal-title":"Elife"},{"key":"10.1016\/j.jhep.2022.08.041_bib15","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1017\/S1355838202026432","article-title":"Hepatitis delta virus ribonucleoproteins shuttle between the nucleus and the cytoplasm","volume":"8","author":"Tavanez","year":"2002","journal-title":"RNA"},{"key":"10.1016\/j.jhep.2022.08.041_bib16","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1136\/gutjnl-2018-316601","article-title":"Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis","volume":"68","author":"Chen","year":"2019","journal-title":"Gut"},{"key":"10.1016\/j.jhep.2022.08.041_bib17","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1093\/infdis\/jiz633","article-title":"Estimating the global prevalence, disease progression, and clinical outcome of hepatitis delta virus infection","volume":"221","author":"Miao","year":"2020","journal-title":"J\u00a0Infect Dis"},{"key":"10.1016\/j.jhep.2022.08.041_bib18","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.jhep.2020.04.008","article-title":"The global prevalence of hepatitis D virus infection: systematic review and meta-analysis","volume":"73","author":"Stockdale","year":"2020","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.08.041_bib19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/hep.27102","article-title":"Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta","volume":"60","author":"Heidrich","year":"2014","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.08.041_bib20","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1053\/j.gastro.2014.04.030","article-title":"Strategies to inhibit entry of HBV and HDV into hepatocytes","volume":"147","author":"Urban","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhep.2022.08.041_bib21","doi-asserted-by":"crossref","first-page":"e81","DOI":"10.1016\/S0618-8278(19)30141-0","article-title":"GS-13 \u2013 final results of a multicenter, open-label phase 2 clinical trial (MYR203) to assess safety and efficacy of myrcludex B in cwith PEG-interferon alpha 2a in patients with chronic HBV\/HDV co-infection","volume":"70","author":"Wedemeyer","year":"2019","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.08.041_bib22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jhep.2018.02.021","article-title":"Hepatitis D virus replication is sensed by MDA5 and induces IFN-beta\/lambda responses in hepatocytes","volume":"69","author":"Zhang","year":"2018","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.08.041_bib23","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1128\/JVI.76.8.3709-3719.2002","article-title":"Parameters of human hepatitis delta virus genome replication: the quantity, quality, and intracellular distribution of viral proteins and RNA","volume":"76","author":"Gudima","year":"2002","journal-title":"J\u00a0Virol"},{"key":"10.1016\/j.jhep.2022.08.041_bib24","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1128\/jvi.68.6.4063-4066.1994","article-title":"The middle hepatitis B virus envelope protein is not necessary for infectivity of hepatitis delta virus","volume":"68","author":"Sureau","year":"1994","journal-title":"J\u00a0Virol"},{"key":"10.1016\/j.jhep.2022.08.041_bib25","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.jhep.2015.10.030","article-title":"Evidence that hepatitis B virus replication in mouse cells is limited by the lack of a host cell dependency factor","volume":"64","author":"Lempp","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.08.041_bib26","doi-asserted-by":"crossref","first-page":"13881","DOI":"10.1074\/jbc.M900818200","article-title":"The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA","volume":"284","author":"Li","year":"2009","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jhep.2022.08.041_bib27","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1093\/nar\/gkp059","article-title":"The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA","volume":"37","author":"Pippig","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jhep.2022.08.041_bib28","doi-asserted-by":"crossref","first-page":"9700","DOI":"10.1074\/jbc.M807365200","article-title":"Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2","volume":"284","author":"Bamming","year":"2009","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jhep.2022.08.041_bib29","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.jhep.2022.05.023","article-title":"Hepatitis D virus-induced interferon response and administered interferons control cell division-mediated virus spread","volume":"77","author":"Zhang","year":"2022","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.08.041_bib30","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.jhep.2020.06.038","article-title":"Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta","volume":"73","author":"Roulot","year":"2020","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.08.041_bib31","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.immuni.2015.11.001","article-title":"Isoforms of RNA-editing enzyme ADAR1 independently control nucleic acid sensor MDA5-driven autoimmunity and multi-organ development","volume":"43","author":"Pestal","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.jhep.2022.08.041_bib32","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1126\/science.aac7049","article-title":"RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself","volume":"349","author":"Liddicoat","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.jhep.2022.08.041_bib33","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2021109760","article-title":"RNA sensing via the RIG-I-like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency","volume":"41","author":"Stok","year":"2022","journal-title":"EMBO J"},{"key":"10.1016\/j.jhep.2022.08.041_bib34","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1002\/hep.29050","article-title":"Laboratory of genetics and physiology 2 (LGP2) plays an essential role in hepatitis C virus infection-induced interferon responses","volume":"65","author":"Hei","year":"2017","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.08.041_bib35","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1038\/s41467-018-05745-w","article-title":"Nuclear-resident RIG-I senses viral replication inducing antiviral immunity","volume":"9","author":"Liu","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.jhep.2022.08.041_bib36","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1136\/gutjnl-2017-314713","article-title":"Hepatitis delta virus persists during liver regeneration and is amplified through cell division both in\u00a0vitro and in\u00a0vivo","volume":"68","author":"Giersch","year":"2019","journal-title":"Gut"},{"key":"10.1016\/j.jhep.2022.08.041_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0022415","article-title":"Interferon impedes an early step of hepatitis delta virus infection","volume":"6","author":"Han","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.jhep.2022.08.041_bib38","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41587-021-01037-9","article-title":"Pre-activated antiviral innate immunity in the upper airways controls\u00a0early SARS-CoV-2 infection in children","volume":"40","author":"Loske","year":"2021","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.jhep.2022.08.041_bib39","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1086\/382133","article-title":"Quantitation of the level of hepatitis delta virus RNA in serum, by real-time polymerase chain reaction \u2013 and its possible correlation with the clinical stage of liver disease","volume":"189","author":"Yamashiro","year":"2004","journal-title":"J\u00a0Infect Dis"},{"key":"10.1016\/j.jhep.2022.08.041_bib40","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.jhep.2019.12.028","article-title":"Hepatitis delta genotype 5 is associated with favourable disease outcome and better response to treatment compared to genotype 1","volume":"72","author":"Spaan","year":"2020","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.08.041_bib41","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/s41423-020-00602-7","article-title":"Regulation of RIG-I-like receptor-mediated signaling: interaction between host and viral factors","volume":"18","author":"Onomoto","year":"2021","journal-title":"Cell Mol Immunol"}],"container-title":["Journal of Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827822031130?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827822031130?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T19:47:26Z","timestamp":1759175246000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168827822031130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["S0168827822031130"],"URL":"https:\/\/doi.org\/10.1016\/j.jhep.2022.08.041","relation":{},"ISSN":["0168-8278"],"issn-type":[{"value":"0168-8278","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Effect of variants in LGP2 on MDA5-mediated activation of interferon response and suppression of hepatitis D virus replication","name":"articletitle","label":"Article Title"},{"value":"Journal of Hepatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhep.2022.08.041","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.","name":"copyright","label":"Copyright"}]}}