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J. Virol. doi:10.1128/JVI.01568-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Primary human splenic macrophages, but not T or B cells, are the principal target cells for dengue virus infection in vitro

Departments of Biology, Medicine, Microbiology and Immunology, Pathology and Laboratory Medicine. University of Rochester, Rochester, New York 14642

^* To whom correspondence should be addressed. Email: xia_jin{at}urmc.rochester.edu.

	Abstract

Understanding the pathogenesis of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) requires the precise identification of dengue virus (DV) permissive target cells. In a previous study using un-fractionated human peripheral blood mononuclear cells, we found that monocytes, but not B or T cells, were the principal DV-permissive cells in the absence of pooled dengue-immune human sera (PHS) and the major mediators of antibody-dependent enhancement in the presence of PHS. To further identify DV-permissive target cells in other tissues and organs, we isolated human splenic mononuclear cells (MNCs), inoculated them with DV2 (strain 16681) in the presence or absence of PHS, and assessed their infection either directly using flow cytometry and RT-PCR assays, or indirectly by plaque assay. We found that in the absence of PHS, a small proportion of splenic macrophages appeared to be positive for DV antigens in comparison to staining controls by the flow cytometric assay (0.77±1.00% vs. 0.18±0.12%; p=0.07); and that viral RNA was detectable by the RT-PCR assay in MNCs exposed to DV. Additionally, supernatants from cultures of DV-exposed MNCs contained infectious virions that were readily detectable by plaque assay. The magnitude of infection was significantly enhanced in splenic macrophages in the presence of highly diluted PHS (5.41±3.53% vs. 0.77±1.00%; p=0.001). In contrast, primary T and B cells were not infected either in the presence or absence of PHS. These results provide evidence, for the first time, that human primary splenic macrophages, rather than B or T cells, are the principal DV-permissive cells in the spleen; and that they may be uniquely important in the initial steps of immune enhancement that leads to DHF/DSS in some DV-infected individuals.