{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:14:39Z","timestamp":1793060079768,"version":"4.5.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Hepatitis E virus (HEV) is a common cause of acute hepatitis that results in high mortality in pregnant women and may establish chronic infections in immunocompromised patients. We demonstrate for the first time that alpha interferon (IFN-\u03b1) and ribavirin inhibit\n            <jats:italic>in vitro<\/jats:italic>\n            HEV replication in both a subgenomic replicon and an infectious culture system based on a genotype 3 strain. IFN-\u03b1 showed a moderate but significant synergism with ribavirin. These findings corroborate the reported clinical effectiveness of both drugs. In addition, the antiviral activity of ribavirin against wild-type genotype 1, 2, and 3 strains was confirmed by immunofluorescence staining. Furthermore, the\n            <jats:italic>in vitro<\/jats:italic>\n            activity of ribavirin depends on depletion of intracellular GTP pools, which is evident from the facts that (i) other GTP-depleting agents (5-ethynyl-1-\u03b2-\n            <jats:sc>d<\/jats:sc>\n            -ribofuranosylimidazole-4-carboxamide [EICAR] and mycophenolic acid) inhibit viral replication, (ii) exogenously added guanosine reverses the antiviral effects, and (iii) a strong correlation (\n            <jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            = 0.9998) exists between the antiviral activity and GTP depletion of ribavirin and other GTP-depleting agents.\n          <\/jats:p>","DOI":"10.1128\/aac.01795-13","type":"journal-article","created":{"date-parts":[[2013,10,22]],"date-time":"2013-10-22T02:41:14Z","timestamp":1382409674000},"page":"267-273","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":160,"title":["Ribavirin Inhibits\n            <i>In Vitro<\/i>\n            Hepatitis E Virus Replication through Depletion of Cellular GTP Pools and Is Moderately Synergistic with Alpha Interferon"],"prefix":"10.1128","volume":"58","author":[{"given":"Yannick","family":"Debing","sequence":"first","affiliation":[{"name":"Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne U.","family":"Emerson","sequence":"additional","affiliation":[{"name":"Molecular Hepatitis, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"Wang","sequence":"additional","affiliation":[{"name":"Erasmus MC-University Medical Center, Department of Gastroenterology &amp; Hepatology, Rotterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuwei","family":"Pan","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium"},{"name":"Erasmus MC-University Medical Center, Department of Gastroenterology &amp; Hepatology, Rotterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Balzarini","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Dallmeier","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Neyts","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61849-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24674"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25505"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-82-10-2449"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1609.100444"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.21536"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1808.111659"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00800-12"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2011.03.019"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/653943"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2013.03.001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.050"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1338115"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2011.06.004"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12114"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-012-0682-0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00146-12"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.034330.112"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018878108"},{"key":"e_1_3_2_21_2","volume-title":"Guide for the care and use of laboratory animals","author":"National Research Council","year":"2011","unstructured":"National Research Council. 2011. 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