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| Content Provider | PubMed Central |
|---|---|
| Author | Boonnak, Kobporn Slike, Bonnie M. Burgess, Timothy H. Mason, Randall M. Wu, Shuenn-jue Sun, Peifang Porter, Kevin Rudiman, Irani Fianza Yuwono, Djoko Puthavathana, Pilaipan Marovich, Mary A. |
| 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. |
| Related Links | http://dx.doi.org/10.1128/jvi.02484-07 |
| Ending Page | 3951 |
| Page Count | 13 |
| Starting Page | 3939 |
| File Format | |
| ISSN | 0022538X |
| e-ISSN | 10985514 |
| Journal | Journal of Virology |
| Issue Number | 8 |
| Volume Number | 82 |
| Language | English |
| Publisher | American Society for Microbiology (ASM) |
| Publisher Date | 2008-04-15 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology (ASM) |
| Subject Keyword | Immunology Virology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Virology Immunology Microbiology Insect Science |
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