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

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.

Received June 23, 2008. Accepted for publication November 11, 2008.

Acknowledgments: We thank Jennifer Kyle, Katherine Williams, Milena Gutierrez, Carolina Pérez, Fei Lin, and Dianna Edgil for their contributions to this work, and the staff of the University of California Berkeley Northwest Animal Facility for animal research support.

^* Address correspondence to Eva Harris, Division of Infectious Diseases, School of Public Health, University of California Berkeley, 1 Barker Hall, Berkeley, CA 94720-7354. E-mail: eharris{at}berkeley.edu

Authors’ addresses: Scott J. Balsitis, Josefina Coloma, Diana Flores, and Eva Harris, Division of Infectious Diseases, School of Public Health, University of California Berkeley, 1 Barker Hall, Berkeley, CA 94720-7354. Glenda Castro, Microbiologia, Biologia Molecular, Infectious Diseases Hospital Jose Rodriguez Marideña, Julian Coronel y Esmeraldas, Postal 09-04-465P, Guayaquil, Ecuador. Aracely Alava, Division of Research and Microbiological Diagnostics, National Institute of Hygiene and Tropical Medicine Leopoldo Izquieta Perez, Julian Coronel y Esmeraldas 901-905, Postal 6224, Guayaquil, Ecuador. James H. McKerrow, Box 2550, University of California San Francisco, QB3, Mission Bay, San Francisco, CA 94158. P. Robert Beatty, Department of Molecular and Cell Biology, University of California Berkeley, 142 Life Sciences Addition, Berkeley, CA 94720-3200.

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