Tropism of Dengue Virus in Mice and Humans Defined by Viral Nonstructural Protein 3-Specific Immunostaining

Scott J. Balsitis Division of Infectious Diseases, School of Public Health, and Department of Molecular and Cell Biology, University of California, Berkeley, California; Hospital de Infectología, Ministerio de Salud, Guayaquil, Ecuador; Instituto Nacional de Higiene, Ministerio de Salud, Guayaquil, Ecuador; Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California

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Josefina Coloma Division of Infectious Diseases, School of Public Health, and Department of Molecular and Cell Biology, University of California, Berkeley, California; Hospital de Infectología, Ministerio de Salud, Guayaquil, Ecuador; Instituto Nacional de Higiene, Ministerio de Salud, Guayaquil, Ecuador; Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California

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Glenda Castro Division of Infectious Diseases, School of Public Health, and Department of Molecular and Cell Biology, University of California, Berkeley, California; Hospital de Infectología, Ministerio de Salud, Guayaquil, Ecuador; Instituto Nacional de Higiene, Ministerio de Salud, Guayaquil, Ecuador; Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California

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Aracely Alava Division of Infectious Diseases, School of Public Health, and Department of Molecular and Cell Biology, University of California, Berkeley, California; Hospital de Infectología, Ministerio de Salud, Guayaquil, Ecuador; Instituto Nacional de Higiene, Ministerio de Salud, Guayaquil, Ecuador; Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California

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Diana Flores Division of Infectious Diseases, School of Public Health, and Department of Molecular and Cell Biology, University of California, Berkeley, California; Hospital de Infectología, Ministerio de Salud, Guayaquil, Ecuador; Instituto Nacional de Higiene, Ministerio de Salud, Guayaquil, Ecuador; Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California

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James H. McKerrow Division of Infectious Diseases, School of Public Health, and Department of Molecular and Cell Biology, University of California, Berkeley, California; Hospital de Infectología, Ministerio de Salud, Guayaquil, Ecuador; Instituto Nacional de Higiene, Ministerio de Salud, Guayaquil, Ecuador; Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California

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P. Robert Beatty Division of Infectious Diseases, School of Public Health, and Department of Molecular and Cell Biology, University of California, Berkeley, California; Hospital de Infectología, Ministerio de Salud, Guayaquil, Ecuador; Instituto Nacional de Higiene, Ministerio de Salud, Guayaquil, Ecuador; Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California

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Eva Harris Division of Infectious Diseases, School of Public Health, and Department of Molecular and Cell Biology, University of California, Berkeley, California; Hospital de Infectología, Ministerio de Salud, Guayaquil, Ecuador; Instituto Nacional de Higiene, Ministerio de Salud, Guayaquil, Ecuador; Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, California

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Previous attempts to define dengue virus (DENV) tropism in human autopsy tissues have detected DENV antigens that are abundant in circulation during severe dengue, and thus may be present in uninfected cells. To better define DENV tropism, we performed immunostaining for the DENV2 nonstructural protein 3 (NS3) in humans and in a mouse model of DENV infection. In mice, NS3 was detected in phagocytes of the spleen and lymph node, hepatocytes in liver, and myeloid cells in bone marrow. In human autopsy tissues, NS3 was present in phagocytes in lymph node and spleen, alveolar macrophages in lung, and perivascular cells in brain. This protein was also found in hepatocytes in liver and endothelial cells in spleen, although NS3 was not present in endothelium in any other tissue. Thus, NS3-specific immunostaining supports roles for infected phagocytes, hepatocytes, and, to a limited degree, endothelial cells in the pathogenesis of severe dengue.

Author Notes

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