dengue virus tropism in humanized mice recapitulates human dengue fever登革病毒取向在人源化小鼠概括人类登革热.pdfVIP

Dengue Virus Tropism in Humanized Mice Recapitulates Human Dengue Fever Javier Mota, Rebeca Rico-Hesse* Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas, United States of America Abstract Animal models of dengue virus disease have been very difficult to develop because of the virus’ specificity for infection and replication in certain human cells. We developed a model of dengue fever in immunodeficient mice transplanted with human stem cells from umbilical cord blood. These mice show measurable signs of dengue disease as in humans (fever, viremia, erythema and thrombocytopenia), and after infection with the most virulent strain of dengue serotype 2, humanized mice showed infection in human cells in bone marrow, spleen and blood. Cytokines and chemokines were secreted by these human cells into the mouse bloodstream. We demonstrated that the pathology of dengue virus infection in these mice follows that reported in human patients, making this the first valid and relevant model for studying dengue fever pathogenesis in humans. Citation: Mota J, Rico-Hesse R (2011) Dengue Virus Tropism in Humanized Mice Recapitulates Human Dengue Fever. PLoS ONE 6(6): e20762. doi:10.1371/ journal.pone.0020762 Editor: Todd Davis, Centers for Disease Control and Prevention, United States of America Received February 7, 2011; Accepted May 8, 2011; Published June 10, 2011 Copyright: 2011 Mota, Rico-Hesse. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Funding was provided by National Institutes of Health (NIH) grant R01AI50123 to RRH. The funders had no role in stu