Publication: Cell type specificity and host genetic polymorphisms influence antibody-dependent enhancement of dengue virus infection
Issued Date
2011-02-01
Resource Type
ISSN
10985514
0022538X
0022538X
Other identifier(s)
2-s2.0-78951488927
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Virology. Vol.85, No.4 (2011), 1671-1683
Suggested Citation
Kobporn Boonnak, Kaitlyn M. Dambach, Gina C. Donofrio, Boonrat Tassaneetrithep, Mary A. Marovich Cell type specificity and host genetic polymorphisms influence antibody-dependent enhancement of dengue virus infection. Journal of Virology. Vol.85, No.4 (2011), 1671-1683. doi:10.1128/JVI.00220-10 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/11363
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Cell type specificity and host genetic polymorphisms influence antibody-dependent enhancement of dengue virus infection
Abstract
Antibody-dependent enhancement (ADE) is implicated in severe, usually secondary, dengue virus (DV) infections. Preexisting heterotypic antibodies, via their Fc-gamma receptor (FcγR) interactions, may increase disease severity through enhanced target cell infection. Greater numbers of infected target cells may contribute to higher viremia and excess cytokine levels often observed in severe disease. Monocytes, macrophages, and immature and mature dendritic cells (DC) are considered major cellular targets of DV. Apheresis of multiple donors allowed isolation of autologous primary myeloid target cell types for head-to-head comparison of infection rates, viral output, a nd cytokine production under direct infection (without antibody) or ADE conditions (with antibody). All studied cell types except immature DC supported ADE. All cells undergoing ADE secreted proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-α] ) at enhancement titers, but distinct cell-type-specific patterns were observed for other relevant proteins (alpha/ beta interferon [IFN-α/β] and IL-10). Macrophages produced type I interferons (IFN-α/β) that were modulated by ADE. Mature DC mainly secreted IFN-β. Interestingly, only monocytes secreted IL-10, and only upon antibody-enhanced infection. While ADE infection rates were remarkably consistent in monocytes (10 to 15%) across donors, IL-10 protein levels varied according to previously described regulatory single nucleotide polymorphisms (SNPs) in the IL-10 promoter region. The homozygous GCC haplotype was associated with high-level IL-10 secretion, while the ACC and ATA haplotypes produced intermediate and low levels of IL-10, respectively. Our data suggest that ADE effects are cell type specific, are influenced by host genetics, and, depending on relative infection rates, may further contribute to the complexity of DV pathogenesis. Copyright © 2011, American Society for Microbiology. All Rights Reserved.