Journal Article

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

Tang, Kin Fai, Kaliaperumal, Nivashini, Hibberd, Martin L., Lin, Chao-Nan, Zhang, Qian, Krishnan, Manoj N., Tan, Hwee Cheng, Lok, Shee Mei, Zhang, Summer Li-Xin, Connolly, John E., Hanson, Brendon J., Ooi, Eng Eong, Chan, Kuan Rong, Chan, Soh Ha, Pei Chiew Lim, Angeline, Ong, Eugenia Z.

2014

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Antibodies / Antibody-Dependent Enhancement - immunology / Antibody-Dependent Enhancement - physiology / Antigens, CD - metabolism / Antivirals / Biological Sciences / Blotting, Western / Cell Line / Cell lines / crosslinking / dendritic cells / Dengue / Dengue - immunology / Dengue - physiopathology / Dengue fever / Dengue virus / Dengue Virus - metabolism / Dengue Virus - physiology / Genes / Humans / Immunoglobulins / immunologic receptors / Infections / Kinases / Leukocyte Immunoglobulin-like Receptor B1 / Leukocytes / macrophages / Microarray Analysis / Monocytes / non-specific protein-tyrosine kinase / Receptors / Receptors, IgG - metabolism / Receptors, Immunologic - metabolism / RNA, Small Interfering - genetics / secondary infection / serotypes / Vector-borne diseases / Viruses