Publication: Role of dendritic cells in antibody-dependent enhancement of dengue virus infection
Issued Date
2008-04-01
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ISSN
0022538X
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2-s2.0-41949101934
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Virology. Vol.82, No.8 (2008), 3939-3951
Suggested Citation
Kobporn Boonnak, Bonnie M. Slike, Timothy H. Burgess, Randall M. Mason, Shuenn Jue Wu, Peifang Sun, Kevin Porter, Irani Fianza Rudiman, Djoko Yuwono, Pilaipan Puthavathana, Mary A. Marovich Role of dendritic cells in antibody-dependent enhancement of dengue virus infection. Journal of Virology. Vol.82, No.8 (2008), 3939-3951. doi:10.1128/JVI.02484-07 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/18747
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Title
Role of dendritic cells in antibody-dependent enhancement of dengue virus infection
Abstract
Dengue viruses (DV), composed of four distinct serotypes (DV1 to DV4), cause 50 to 100 million infections annually. Durable homotypic immunity follows infection but may predispose to severe subsequent heterotypic infections, a risk conferred in part by the immune response itself. Antibody-dependent enhancement (ADE), a process best described in vitro, is epidemiologically linked to complicated DV infections, especially in Southeast Asia. Here we report for the first time the ADE phenomenon in primary human dendritic cells (DC), early targets of DV infection, and human cell lines bearing Fc receptors. We show that ADE is inversely correlated with surface expression of DC-SIGN (DC-specific intercellular adhesion molecule-3-grabbing nonintegrin) and requires Fc gamma receptor IIa (FcγRIIa). Mature DC exhibited ADE, whereas immature DC, expressing higher levels of DC-SIGN and similar FcγRIIa levels, did not undergo ADE. ADE results in increased intracellular de novo DV protein synthesis, increased viral RNA production and release, and increased infectivity of the supernatants in mature DC. Interestingly, tumor necrosis factor alpha and interleukin-6 (IL-6), but not IL-10 and gamma interferon, were released in the presence of dengue patient sera but generally only at enhancement titers, suggesting a signaling component of ADE. FcγRIIa inhibition with monoclonal antibodies abrogated ADE and associated downstream consequences. DV versatility in entry routes (FcγRIIa or DC-SIGN) in mature DC broadens target options and suggests additional ways for DC to contribute to the pathogenesis of severe DV infection. Studying the cellular targets of DV infection and their susceptibility to ADE will aid our understanding of complex disease and contribute to the field of vaccine development. Copyright © 2008, American Society for Microbiology. All Rights Reserved.