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A glycoprotein mutation known to enhance dendritic cell targeting accentuated both characteristics but when introduced alone, failed to alter the phenotype of the Armstrong strain. The decisive polymerase mutation increased intracellular viral RNA load in plasmacytoid dendritic cells, which we identified as a main initial target cell type in vivo, and increased viremia in the early phase of infection. These findings establish the enhanced replicative capacity as the primary determinant of the Cl13 phenotype. Viral persistence and immunosuppression can, thus, represent a direct consequence of excessive viral replication overwhelming the host's antiviral defense.<\/jats:p>","DOI":"10.1073\/pnas.1011998107","type":"journal-article","created":{"date-parts":[[2010,11,23]],"date-time":"2010-11-23T00:41:46Z","timestamp":1290472906000},"page":"21641-21646","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":97,"title":["Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression"],"prefix":"10.1073","volume":"107","author":[{"given":"Andreas","family":"Bergthaler","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Centre M\u00e9dical Universitaire, University of Geneva, 1211 Geneva, Switzerland;"},{"name":"Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich, 8091 Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Flatz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Centre M\u00e9dical Universitaire, University of Geneva, 1211 Geneva, Switzerland;"},{"name":"Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich, 8091 Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed N.","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich, 8091 Zurich, Switzerland;"},{"name":"Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013University Medicine Berlin, German Rheumatism Research Center, 10117 Berlin, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Centre M\u00e9dical Universitaire, University of Geneva, 1211 Geneva, Switzerland;"},{"name":"World Health Organization Collaborating Centre for Neonatal Vaccinology, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edit","family":"Horvath","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich, 8091 Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"L\u00f6hning","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich, 8091 Zurich, Switzerland;"},{"name":"Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2013University Medicine Berlin, German Rheumatism Research Center, 10117 Berlin, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Pinschewer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Centre M\u00e9dical Universitaire, University of Geneva, 1211 Geneva, Switzerland;"},{"name":"Institute of Experimental Immunology, Department of Pathology, University Hospital Zurich, 8091 Zurich, Switzerland;"},{"name":"World Health Organization Collaborating Centre for Neonatal Vaccinology, University of Geneva, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,11,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.64.2.183"},{"key":"e_1_3_3_2_2","first-page":"1","article-title":"Lymphocytic choriomeningitis virus and immunology","volume":"263","author":"Zinkernagel RM","year":"2002","unstructured":"RM Zinkernagel, Lymphocytic choriomeningitis virus and immunology. 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