{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:09:29Z","timestamp":1792786169832,"version":"4.5.0"},"reference-count":85,"publisher":"Microbiology Society","issue":"2","funder":[{"name":"Department of Science and Technology","award":["LS\/358\/2017"],"award-info":[{"award-number":["LS\/358\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,21]]},"abstract":"<jats:p>Hepatitis E virus (HEV) egresses from infected hepatocytes as quasienveloped particles containing open reading frame 3 (ORF3) protein. HEV ORF3 (small phosphoprotein) interacts with host proteins to establish a favourable environment for virus replication. It is a functional viroporin that plays an important role during virus release. Our study provides evidence that pORF3 plays a pivotal role in inducing Beclin1-mediated autophagy that helps HEV-1 replication as well as its exit from cells. The ORF3 interacts with host proteins involved in regulation of transcriptional activity, immune response, cellular and molecular processes, and modulation of autophagy, by interacting with proteins, DAPK1, ATG2B, ATG16L2 and also several histone deacetylases (HDACs). For autophagy induction, the ORF3 utilizes non-canonical NF-\u03baB2 pathway and sequesters p52NF-\u03baB and HDAC2 to upregulate DAPK1 expression, leading to enhanced Beclin1 phosphorylation. By sequestering several HDACs, HEV may prevent histone deacetylation to maintain overall cellular transcription intact to promote cell survival. Our findings highlight a novel crosstalk between cell survival pathways participating in ORF3-mediated autophagy<\/jats:p>","DOI":"10.1099\/jgv.0.001824","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T12:18:45Z","timestamp":1676981925000},"source":"Crossref","is-referenced-by-count":9,"title":["Modulation of cellular autophagy by genotype 1 hepatitis E virus ORF3 protein"],"prefix":"10.1099","volume":"104","author":[{"given":"Manjita","family":"Srivastava","sequence":"first","affiliation":[{"name":"Division of Hepatitis, National Institute of Virology, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5657-9996","authenticated-orcid":false,"given":"Prudhvi Lal","family":"Bhukya","sequence":"additional","affiliation":[{"name":"ICMR-National Animal Resource Facility for Biomedical Research, Hyderabad, India"},{"name":"Division of Hepatitis, National Institute of Virology, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneesh Kumar","family":"Barman","sequence":"additional","affiliation":[{"name":"Laboratory for HIV Research, National Centre for Cell Sciences, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Bhise","sequence":"additional","affiliation":[{"name":"Division of Hepatitis, National Institute of Virology, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-2268","authenticated-orcid":false,"given":"Kavita S.","family":"Lole","sequence":"additional","affiliation":[{"name":"Division of Hepatitis, National Institute of Virology, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001778"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9020331"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1007\/s12038-008-0064-1"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v27.i20.2458"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005521"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.3390\/v13010075"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1338110"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890400208"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2008.02032.x"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399499001271"},{"key":"R11","first-page":"1059","article-title":"Cross-reactive immunity against different strains of the hepatitis E virus transferable by simian and human sera","volume":"318","author":"Pillot","year":"1995","journal-title":"C R Acad Sci III"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.1987"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.27.061406.093749"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.09.023"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.09.021"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C700195200"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-12-1257"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1846"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e08-01-0080"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1854"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1159\/000346388"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2011.09.007"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134012"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1890"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02415-12"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.14.8742-8749.2005"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308971"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01575-20"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.05.026"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00541-07"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02039-06"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1614955114"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100787"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1038\/srep27597"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26975-4"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-218875"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142615"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01475-10"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1038\/srep26827"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.4.8312"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.07.015"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096645"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1159\/000490020"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2018.3688"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001568"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2012.03.003"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1007\/s12154-008-0003-5"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2245"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-9-39"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.1.207-216.1996"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.09.020"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07411.x"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-011-0685-y"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.5.8625"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1126\/science.1205407"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1615\/critrevoncog.2015012997"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1726"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.066910-0"},{"key":"R59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030156"},{"key":"R60","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.10.042"},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.3.7406"},{"key":"R62","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306124200"},{"key":"R63","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.7.13309"},{"key":"R64","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.05.032"},{"key":"R65","doi-asserted-by":"publisher","DOI":"10.4161\/auto.27286"},{"key":"R66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025378"},{"key":"R67","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29105"},{"key":"R68","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00656"},{"key":"R69","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01994-09"},{"key":"R70","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400457200"},{"key":"R71","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701696200"},{"key":"R72","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01228-14"},{"key":"R73","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.09.005"},{"key":"R74","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12191"},{"key":"R75","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02383-15"},{"key":"R76","doi-asserted-by":"publisher","DOI":"10.3109\/1040841X.2013.813899"},{"key":"R77","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618517114"},{"key":"R78","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-013-0931-6"},{"key":"R79","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.03.010"},{"key":"R80","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00323-12"},{"key":"R81","doi-asserted-by":"publisher","DOI":"10.1038\/srep27597"},{"key":"R82","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.70.7.4558-4566.1996"},{"key":"R83","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.9.6345"},{"key":"R84","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2013.1842"},{"key":"R85","doi-asserted-by":"publisher","DOI":"10.1101\/2020.05.11.088385"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/jgv.0.001824?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T12:18:48Z","timestamp":1676981928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/jgv.0.001824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,21]]},"references-count":85,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2,21]]}},"URL":"https:\/\/doi.org\/10.1099\/jgv.0.001824","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,21]]}}}