Publication: Mechanisms of immune evasion induced by a complex of dengue virus and preexisting enhancing antibodies
Issued Date
2010-03-12
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ISSN
00221899
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2-s2.0-77749295592
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Infectious Diseases. Vol.201, No.6 (2010), 923-935
Suggested Citation
Sukathida Ubol, Weerawat Phuklia, Siripen Kalayanarooj, Naphak Modhiran Mechanisms of immune evasion induced by a complex of dengue virus and preexisting enhancing antibodies. Journal of Infectious Diseases. Vol.201, No.6 (2010), 923-935. doi:10.1086/651018 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/29733
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Title
Mechanisms of immune evasion induced by a complex of dengue virus and preexisting enhancing antibodies
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Abstract
We have found that dengue virus (DENV) not only uses preexisting enhancing antibodies to promote its entry into Fc receptor-bearing cells but also exploits enhancing antibodies for intracellular immune evasion through 2 mechanisms. In the first mechanism, entry of DENV-antibody complexes into human monocytic cells activates negative regulators, dihydroxyacetone kinase and autophagy-related 5-autophagy-related 12, which then disrupt the retinoic acide incucible gene I and melanoma differentiation associated gene 5 signaling cascade and disable type 1 interferon production, leading to suppression of interferon-mediated antiviral responses. In the second mechanism, the immune evasion was found to be mediated by the suppressive cytokine interleukin 10 (IL-10). High levels of IL-10 activated expression of suppressor of cytokine signaling 3 gene, which subsequently inactivated the Janus kinase-signal transducer and activator of transcription pathway. Inhibition of IL-10 production by small interfering RNA down-regulated suppressor of cytokine signaling 3 gene expression, restored inducible nitric oxide synthase gene expression, and suppressed DENV replication. Importantly, we were able to demonstrate that these 2 loops of suppression occurred in patients with severe secondary dengue infection (dengue hemorrhagic fever) but not in patients with mild secondary dengue infection (dengue fever). © 2010 by the Infectious Diseases Society of America. All rights reserved.