{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:46:46Z","timestamp":1791161206055,"version":"4.1.0"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"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":["J Virol"],"published-print":{"date-parts":[[2000,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>We have previously shown that hepatitis B virus (HBV) replication is inhibited noncytopathically in the livers of transgenic mice following injection of HBV-specific cytotoxic T lymphocytes (CTLs) or infection with unrelated hepatotropic viruses, including lymphocytic choriomeningitis virus (LCMV) and adenovirus. These effects are mediated by gamma interferon (IFN\u03b3), tumor necrosis factor alpha (TNF\u03b1), and IFN\u03b1\/\u03b2. In the present study, we crossed HBV transgenic mice with mice genetically deficient for IFN\u03b3 (IFN\u03b3KO), the TNF\u03b1 receptor (TNF\u03b1RKO), or the IFN\u03b1\/\u03b2 receptor (IFN\u03b1\/\u03b2RKO) in order to determine the relative contribution of each cytokine to the antiviral effects observed in each of these systems. Interestingly, we showed that HBV replicates in unmanipulated IFN\u03b3KO and IFN\u03b1\/\u03b2RKO mice at levels higher than those observed in control mice, implying that baseline levels of these cytokines control HBV replication in the absence of inflammation. We also showed that IFN\u03b3 mediates most of the antiviral effect of the CTLs while IFN\u03b1\/\u03b2 is primarily responsible for the early inhibitory effect of LCMV and adenovirus on HBV replication. In addition, we showed that the hepatic induction of IFN\u03b1\/\u03b2 observed after injection of poly(I \u00b7 C) is sufficient to inhibit HBV replication and that a similar antiviral effect is achieved by systemic administration of very high doses of IFN\u03b1. We also compared the relative sensitivity of LCMV and adenovirus to control by IFN\u03b3, TNF\u03b1, or IFN\u03b1\/\u03b2 in these animals. Importantly, IFN\u03b1\/\u03b2RKO mice, and to a lesser extent IFN\u03b3KO mice, showed higher hepatic levels of LCMV RNA and adenovirus DNA and RNA than control mice, underscoring the importance of both interferons in controlling these other viral infections as well.<\/jats:p>","DOI":"10.1128\/jvi.74.5.2255-2264.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:06:37Z","timestamp":1027749997000},"page":"2255-2264","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":224,"title":["Relative Sensitivity of Hepatitis B Virus and Other Hepatotropic Viruses to the Antiviral Effects of Cytokines"],"prefix":"10.1128","volume":"74","author":[{"given":"Heike","family":"McClary","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick","family":"Koch","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis V.","family":"Chisari","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca G.","family":"Guidotti","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.5.1541"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/316552a0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.4.2630-2637.1998"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.13.040195.000333"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8456300"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.18.9814"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.10.4589"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(99)80068-X"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(96)80034-3"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80295-2"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.10.6158-6169.1995"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.825"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-437X(93)90126-A"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.58.2.782"},{"key":"e_1_3_2_16_2","first-page":"165","article-title":"Transgenic mice as chemotherapeutic model for hepatitis B virus infection","volume":"3","author":"Morrey J. 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