Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/119247
Title: A MECHANISTIC INVESTIGATION OF FCγR SIGNALING DURING ANTIBODY-ENHANCED DENGUE INFECTION
Authors: ONG ZIYING, EUGENIA
Keywords: Dengue, Fc gamma receptor, antibody-dependent enhancement, LILRB1, phagosome, compartmentalization
Issue Date: 26-Feb-2015
Citation: ONG ZIYING, EUGENIA (2015-02-26). A MECHANISTIC INVESTIGATION OF FCγR SIGNALING DURING ANTIBODY-ENHANCED DENGUE INFECTION. ScholarBank@NUS Repository.
Abstract: Viruses must evade the host innate defenses for replication and dengue is no exception. During secondary infection with a heterologous dengue virus (DENV) serotype, DENV is opsonized with sub- or non-neutralizing antibodies that enhance infection of monocytes and dendritic cells through Fc-gamma receptors, a process termed antibody-dependent enhancement (ADE). However, cross-linking of activating Fc-gamma receptors signals an early antiviral response by inducing the type-I interferon-stimulated genes (ISGs). To escape this antiviral response, we demonstrate that antibody-opsonized DENV co-ligates leukocyte immunoglobulin-like receptor-B1 (LILRB1), which recruits Src homology phosphatase-1 (SHP-1) to dephosphorylate spleen tyrosine kinase (Syk) and reduce ISG induction. As Syk also regulates phagosomal maturation, it is possible that compartmentalization of DENV-containing phagosomes could be altered by differential Syk phosphorylation, thereby influencing the outcome of ADE. Indeed, we observed that LILRB1 co-ligation reduced levels of phagosomal acidification, which could be reversed by inhibiting SHP-1. Collectively, we have shown that DENV co-ligates LILRB1 to both attenuate the expression of ISGs and the rapid acidification in the phagolysosomal pathway, ensuring intracellular survival during antibody-enhanced dengue infection.
URI: http://scholarbank.nus.edu.sg/handle/10635/119247
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