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Monocytes, but not T or B cells, are the principal target cells for dengue virus (DV) infection among human peripheral blood mononuclear cells
Author(s) -
Kou Zhihua,
Quinn Matthew,
Chen Huiyuan,
Rodrigo W.W. Shanaka I.,
Rose Robert C.,
Schlesinger Jacob J.,
Jin Xia
Publication year - 2008
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.21051
Subject(s) - cd14 , peripheral blood mononuclear cell , dengue virus , virology , dengue fever , antibody , monoclonal antibody , flow cytometry , immune system , biology , monocyte , virus , antigen , vero cell , immunology , microbiology and biotechnology , in vitro , biochemistry
A better understanding of the pathogenesis of dengue hemorrhagic fever and dengue shock syndrome requires the precise identification of dengue virus (DV) permissive target cells. To examine the relative DV permissiveness among cell subsets, we inoculated unfractionated human peripheral blood mononuclear cells with DV2‐16681 in the presence or absence of pooled DV‐immune human sera (PHS), and assessed infection with fluorescent dye labeled DV‐specific monoclonal antibody and cell surface markers using flow cytometry. We found significantly higher levels of DV antigen staining on DV‐infected than mock‐infected primary monocytes (3.54 ± 3.42% vs. 0.50 ± 0.38%; P = 0.001). The magnitude of infection was markedly enhanced in the presence of highly diluted PHS (10.04 ± 6.10% vs. 3.54 ± 3.42%; P = 0.015). Under identical experimental conditions, primary T or B cells were not infected either with or without the addition of PHS (0.06 ± 0.04% and 0.44 ± 0.22% for T and B cells, respectively). Furthermore, depletion of CD14+ monocytes prior to DV inoculation abrogated the detection of infected cells, and the addition of monoclonal antibodies to either FcγRI (CD64) or FcγRII (CD32) led to a 50–70% reduction in antibody‐dependent enhancement (ADE) of DV infection. Collectively, these results provide further support to the notion that primary monocytes and FcγRs expressed on these cells may be important in the initial steps of immune enhancement observed in some patients with natural DV infection. They also demonstrate that using modern experimental technology, DV infection, and neutralization and enhancement of DV infection can be easily assessed simultaneously in multiple cell types. J. Med. Virol. 80:134–146, 2008. © 2007 Wiley‐Liss, Inc.