{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:09:47Z","timestamp":1782835787776,"version":"3.54.5"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010203","name":"Agriculture Research System of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010203","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Autophagy plays an important role in host antiviral defense. The avian leukosis virus subgroup J (ALV-J) has been shown to inhibit autophagy while promoting viral replication. The underlying autophagic mechanisms, however, are unknown. Cholesterol 25-hydroxylase (CH25H) is a conserved interferon-stimulated gene, which converts cholesterol to a soluble antiviral factor, 25-hydroxycholesterol (25HC). In this study, we further investigated the autophagic mechanism of CH25H resistance to ALV-J in chicken embryonic fibroblast cell lines (DF1). Our results found that overexpression of <jats:italic>CH25H<\/jats:italic> and treatment with 25HC promoted the autophagic markers microtubule-associated protein 1 light chain 3 II (LC3II) and autophagy-related gene 5(ATG5), while decreased autophagy substrate p62\/SQSTM1 (p62) expression in ALV-J infection DF-1 cells. Induction of cellular autophagy also reduces the levels of ALV-J gp85 and p27. ALV-J infection, on the other hand, suppresses autophagic marker protein LC3II expression. These findings suggest that CH25H-induced autophagy is a host defense mechanism that aids in ALV-J replication inhibition. In particular, CH25H interacts with CHMP4B and inhibits ALV-J infection in DF-1 cells by promoting autophagy, revealing a novel mechanism by which CH25H inhibits ALV-J infection. Although the underlying mechanisms are not completely understood, CH25H and 25HC are the first to show inhibiting ALV-J infection <jats:italic>via<\/jats:italic> autophagy.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1093289","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T10:25:28Z","timestamp":1676456728000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Chicken CH25H inhibits ALV-J replication by promoting cellular autophagy"],"prefix":"10.3389","volume":"14","author":[{"given":"Tingting","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqing","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiquan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/03079457.2011.646237","article-title":"The long view: 40 years of avian leukosis research","volume":"41","author":"Payne","year":"2012","journal-title":"Avian Pathol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: A complex web of host defenses","volume":"32","author":"SW","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3390\/v11020132","article-title":"Crosstalk between autophagy and type I interferon responses in innate antiviral immunity","volume":"11","author":"Tian","year":"2019","journal-title":"Viruses"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4161\/auto.2176","article-title":"PKR-dependent autophagic degradation of herpes simplex virus type 1","volume":"2","author":"Talloczy","year":"2006","journal-title":"Autophagy"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00270-12","article-title":"RNase l triggers autophagy in response to viral infections","volume":"86","author":"Chakrabarti","year":"2012","journal-title":"J Virol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/cr.2013.168","article-title":"The machinery of macroautophagy","volume":"24","author":"Feng","year":"2014","journal-title":"Cell Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2008.01.001","article-title":"Autophagy and antiviral immunity","volume":"20","author":"Lee","year":"2008","journal-title":"Curr Opin Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4161\/auto.7.6.15267","article-title":"Autophagy promotes the replication of encephalomyocarditis virus in host cells","volume":"7","author":"Zhang","year":"2011","journal-title":"Autophagy"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4MR0216-079R","article-title":"Autophagy in leukocytes and other cells: Mechanisms, subsystem organization, selectivity, and links to innate immunity","volume":"100","author":"Deretic","year":"2016","journal-title":"J Leukoc Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2016.10.008","article-title":"Bacterial pathogens versus autophagy: Implications for therapeutic interventions","volume":"22","author":"Kimmey","year":"2016","journal-title":"Trends Mol Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0003-6","article-title":"Autophagy during viral infection - a double-edged sword","volume":"16","author":"Choi","year":"2018","journal-title":"Nat Rev Microbiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/1743-422X-10-196","article-title":"Subgroup J avian leukosis virus infection inhibits autophagy in DF-1 cells","volume":"10","author":"Liu","year":"2013","journal-title":"Virol J"},{"key":"B13","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1038\/s41419-020-02841-y","article-title":"ALV-J inhibits autophagy through the GADD45beta\/MEKK4\/P38MAPK signaling pathway and mediates apoptosis following autophagy","volume":"11","author":"Liao","year":"2020","journal-title":"Cell Death Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12027","article-title":"GADD45beta, an anti-tumor gene, inhibits avian leukosis virus subgroup J replication in chickens","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"B15","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.immuni.2012.11.005","article-title":"Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol","volume":"38","author":"Liu","year":"2013","journal-title":"Immunity"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106057","article-title":"Cholesterol 25-hydroxylase inhibits SARS-CoV-2 and other coronaviruses by depleting membrane cholesterol","volume":"39","author":"Wang","year":"2020","journal-title":"EMBO J"},{"key":"B17","doi-asserted-by":"publisher","first-page":"498","DOI":"10.3390\/v11060498","article-title":"Cholesterol-25-hydroxylase is a chicken ISG that restricts ALV-J infection by producing 25-hydroxycholesterol","volume":"11","author":"Xie","year":"2019","journal-title":"Viruses"},{"key":"B18","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.antiviral.2017.04.004","article-title":"Herpes simplex virus type 1 abrogates the antiviral activity of Ch25h via its virion host shutoff protein","volume":"143","author":"You","year":"2017","journal-title":"Antiviral Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"727","DOI":"10.3390\/v12070727","article-title":"Multifaceted functions of CH25H and 25HC to modulate the lipid metabolism, immune responses, and broadly antiviral activities","volume":"12","author":"Zhao","year":"2020","journal-title":"Viruses"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.3390\/ijms19072065","article-title":"Programmed cell death in the pathogenesis of influenza","volume":"19","author":"Fujikura","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s13046-021-01959-x","article-title":"Pyroptosis: A new paradigm of cell death for fighting against cancer","volume":"40","author":"Tan","year":"2021","journal-title":"J Exp Clin Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"6665871","DOI":"10.1155\/2021\/6665871","article-title":"Phylogenetic analysis of ALV-J associated with immune responses in yellow chicken flocks in south China","volume":"2021","author":"Zhang","year":"2021","journal-title":"Mediators Inflammation"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.10.001","article-title":"Cell-cycle regulators and cell death in immunity","volume":"18","author":"Zebell","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.01.018","article-title":"Autophagy in inflammation, infection, and immunometabolism","volume":"54","author":"Deretic","year":"2021","journal-title":"Immunity"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nri3532","article-title":"Autophagy in infection, inflammation and immunity","volume":"13","author":"Deretic","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/cdd.2008.150","article-title":"Classification of cell death: recommendations of the nomenclature committee on cell death 2009","volume":"16","author":"Kroemer","year":"2009","journal-title":"Cell Death Differ"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4161\/auto.4600","article-title":"How to interpret LC3 immunoblotting","volume":"3","author":"Mizushima","year":"2007","journal-title":"Aautophagy"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609876200","article-title":"Structure of Atg5.Atg16, a complex essential for autophagy","volume":"282","author":"Matsushita","year":"2007","journal-title":"J Biol Chem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.4.1907-1916.2005","article-title":"Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells","volume":"73","author":"Fink","year":"2005","journal-title":"Infect Immun"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-018-0252-y","article-title":"Autophagy-dependent cell death","volume":"26","author":"Denton","year":"2019","journal-title":"Cell Death Differ"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11137","article-title":"Cell death: a review of the major forms of apoptosis, necrosis and autophagy","volume":"43","author":"D'Arcy","year":"2019","journal-title":"Cell Biol Int"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2062874","article-title":"Apoptosis and autophagy coordinately shape vector tolerance to arbovirus infection","volume":"18","author":"Wang","year":"2022","journal-title":"Autophagy"},{"key":"B33","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/nri.2015.7","article-title":"Converging roles of caspases in inflammasome activation, cell death and innate immunity","volume":"16","author":"Man","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.774323","article-title":"ACSL1 inhibits ALV-J replication by IFN- signaling and PI3K\/Akt pathway","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"u9433","DOI":"10.1126\/sciadv.aau9433","article-title":"Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or -7","volume":"5","author":"McComb","year":"2019","journal-title":"Sci Adv"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400375","article-title":"Proapoptotic BAX and BAK control multiple initiator caspases","volume":"6","author":"Ruiz-Vela","year":"2005","journal-title":"EMBO Rep"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba4733","article-title":"Mycobacterial EST12 activates a RACK1-NLRP3-gasdermin d pyroptosis-IL-1beta immune pathway","volume":"6","author":"Qu","year":"2020","journal-title":"Sci Adv"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1038\/s41418-022-00947-8","article-title":"Ubiquitination of NLRP3 by gp78\/Insig-1 restrains NLRP3 inflammasome activation","volume":"29","author":"Xu","year":"2022","journal-title":"Cell Death Differ"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aan4144","article-title":"The interaction between IKKalpha and LC3 promotes type I interferon production through the TLR9-containing LAPosome","volume":"11","author":"Hayashi","year":"2018","journal-title":"Sci Signal"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201503023","article-title":"TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity","volume":"210","author":"Kimura","year":"2015","journal-title":"J Cell Biol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.virol.2018.06.017","article-title":"Viral dedication to vigorous destruction of interferon receptors","volume":"522","author":"Xia","year":"2018","journal-title":"Virology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/1743-422X-9-143","article-title":"Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis c virus in cell culture","volume":"9","author":"Gunduz","year":"2012","journal-title":"Virol J"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201701049","article-title":"p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by phosphorylating ULK1","volume":"217","author":"He","year":"2018","journal-title":"J Cell Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4161\/auto.23921","article-title":"Type I interferons induce autophagy in certain human cancer cell lines","volume":"9","author":"Schmeisser","year":"2013","journal-title":"Autophagy"},{"key":"B45","doi-asserted-by":"publisher","first-page":"13232","DOI":"10.3390\/ijms222413232","article-title":"How the innate immune DNA sensing cGAS-STING pathway is involved in autophagy","volume":"22","author":"Zheng","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B46","doi-asserted-by":"publisher","first-page":"10631","DOI":"10.1038\/ncomms10631","article-title":"Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A","volume":"7","author":"Kim","year":"2016","journal-title":"Nat Commun"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.399964","article-title":"RNase l induces autophagy via c-jun n-terminal kinase and double-stranded RNA-dependent protein kinase signaling pathways","volume":"287","author":"Siddiqui","year":"2012","journal-title":"J Biol Chem"},{"key":"B48","doi-asserted-by":"publisher","first-page":"5058","DOI":"10.1038\/s41467-019-12991-z","article-title":"ESCRT-III-driven piecemeal micro-ER-phagy remodels the ER during recovery from ER stress","volume":"10","author":"Loi","year":"2019","journal-title":"Nat Commun"},{"key":"B49","doi-asserted-by":"publisher","first-page":"u7198","DOI":"10.1126\/sciadv.aau7198","article-title":"VPS4 triggers constriction and cleavage of ESCRT-III helical filaments","volume":"5","author":"Maity","year":"2019","journal-title":"Sci Adv"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237268","article-title":"High-speed imaging of ESCRT recruitment and dynamics during HIV virus like particle budding","volume":"15","author":"Gupta","year":"2020","journal-title":"PloS One"},{"key":"B51","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jmb.2012.02.044","article-title":"CC2D1A is a regulator of ESCRT-III CHMP4B","volume":"419","author":"Martinelli","year":"2012","journal-title":"J Mol Biol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"18877","DOI":"10.1038\/s41598-020-75852-6","article-title":"ESCRT-III controls nuclear envelope deformation induced by progerin","volume":"10","author":"Arii","year":"2020","journal-title":"Sci Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1093289\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T10:25:32Z","timestamp":1676456732000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1093289\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,15]]},"references-count":52,"alternative-id":["10.3389\/fimmu.2023.1093289"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1093289","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,15]]},"article-number":"1093289"}}