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To examine the role of PML in vivo, we compared immune responses and virus loads of PML-deficient and control mice infected with lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus (VSV). PML<jats:sup>\u2212\/\u2212<\/jats:sup>mice exhibited accelerated primary footpad swelling reactions to very-low-dose LCMV, higher swelling peaks upon high-dose inoculation, and higher viral loads in the early phase of systemic LCMV infection. T-cell-mediated hepatitis and consequent mortality upon infection with a hepatotropic LCMV strain required 10- to 100-times-lower inocula despite normal cytotoxic T-lymphocyte reactivity in PML<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Furthermore, PML deficiency rendered mice 10 times more susceptible to lethal immunopathology upon intracerebral LCMV inoculation. Accordingly, 10-times-lower VSV inocula elicited specific neutralizing-antibody responses, a replication-based effect not observed with inactivated virus or after immunization with recombinant VSV glycoprotein. These in vivo observations corroborated our results showing more virus production in PML<jats:sup>\u2212\/\u2212<\/jats:sup>fibroblasts. Thus, PML is a contributor to innate immunity, defining host susceptibility to viral infections and to immunopathology.<\/jats:p>","DOI":"10.1128\/jvi.76.8.3810-3818.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:59:40Z","timestamp":1027749580000},"page":"3810-3818","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":96,"title":["Effects of Promyelocytic Leukemia Protein on Virus-Host Balance"],"prefix":"10.1128","volume":"76","author":[{"given":"Weldy V.","family":"Bonilla","sequence":"first","affiliation":[{"name":"Institute of Experimental Immunology, University Hospital, CH-8091 Zurich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Pinschewer","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University Hospital, CH-8091 Zurich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, John Radcliffe Hospital, OX3 9DU Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Rousson","sequence":"additional","affiliation":[{"name":"Department of Biostatistics ISPMZ, University of Zurich, CH-8006 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirella","family":"Gaboli","sequence":"additional","affiliation":[{"name":"Molecular and Developmental Biology Laboratory, Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier P.","family":"Pandolfi","sequence":"additional","affiliation":[{"name":"Molecular and Developmental Biology Laboratory, Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf M.","family":"Zinkernagel","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University Hospital, CH-8091 Zurich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria S.","family":"Salvato","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland Biotechnology Center, Baltimore, Maryland 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Hengartner","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University Hospital, CH-8091 Zurich"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.9.11.5062-5072.1989"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.2.1084"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00196682"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830251236"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.5.2259"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.235"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000149472"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","unstructured":"Battegay M. 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