Leukocyte immunoglobulin-like receptor B1 is critical for antibody-dependent dengue.


Chan, KR; Ong, EZ; Tan, HC; Zhang, SL; Zhang, Q; Tang, KF; Kaliaperumal, N; Lim, AP; Hibberd, ML; Chan, SH; Connolly, JE; Krishnan, MN; Lok, SM; Hanson, BJ; Lin, CN; Ooi, EE; (2014) Leukocyte immunoglobulin-like receptor B1 is critical for antibody-dependent dengue. Proceedings of the National Academy of Sciences of the United States of America, 111 (7). pp. 2722-7. ISSN 0027-8424 DOI: https://doi.org/10.1073/pnas.1317454111

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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 nonneutralizing antibodies that enhance infection of monocytes, macrophages, and dendritic cells via the Fc-gamma receptor (FcγR), a process termed antibody-dependent enhancement of DENV infection. However, this enhancement of DENV infection is curious as cross-linking of activating FcγRs signals an early antiviral response by inducing the type-I IFN-stimulated genes (ISGs). Entry through activating FcγR would thus place DENV in an intracellular environment unfavorable for enhanced replication. Here we demonstrate that, to escape this antiviral response, antibody-opsonized DENV coligates leukocyte Ig-like receptor-B1 (LILRB1) to inhibit FcγR signaling for ISG expression. This immunoreceptor tyrosine-based inhibition motif-bearing receptor recruits Src homology phosphatase-1 to dephosphorylate spleen tyrosine kinase (Syk). As Syk is a key intermediate of FcγR signaling, LILRB1 coligation resulted in reduced ISG expression for enhanced DENV replication. Our findings suggest a unique mechanism for DENV to evade an early antiviral response for enhanced infection.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 24550301
Web of Science ID: 331396500066
URI: http://researchonline.lshtm.ac.uk/id/eprint/2014194

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