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Journal of Virology, December 2007, p. 13325-13334, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01568-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Primary Human Splenic Macrophages, but Not T or B Cells, Are the Principal Target Cells for Dengue Virus Infection In Vitro{triangledown}

Shanley Blackley,1,{dagger} Zhihua Kou,2,{dagger} Huiyuan Chen,2 Matthew Quinn,3 Robert C. Rose,2,3 Jacob J. Schlesinger,2,3 Myra Coppage,4 and Xia Jin2,3*

Departments of Biology,1 Medicine,2 Microbiology and Immunology,3 Pathology and Laboratory Medicine, University of Rochester, Rochester, New York 146424

Received 18 July 2007/ Accepted 24 September 2007

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 unfractionated 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 DV-immune pooled 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 DV type 2 (strain 16681) in the presence or absence of PHS, and assessed their infection either directly using flow cytometry and reverse transcription-PCR (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% versus 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% versus 0.77% ± 1.00%; P = 0.001). In contrast, primary T and B cells were not infected in either 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.

* Corresponding author. Mailing address: Department of Medicine, Infectious Diseases Division, University of Rochester, 601 Elmwood Avenue, Box 689, Room 3-5103, Rochester, NY 14642. Phone: (585) 275-6515. Fax: (585) 442-9328. E-mail: xia_jin{at}urmc.rochester.edu

{triangledown} Published ahead of print on 10 October 2007.

{dagger} S.B. and Z.K. contributed equally to the work presented in this paper.

Journal of Virology, December 2007, p. 13325-13334, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01568-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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