Leukocyte immunoglobulin-like receptor B1 is critical for antibody-dependent dengue.
Chan, Kuan Rong;
Ong, Eugenia Z;
Tan, Hwee Cheng;
Zhang, Summer Li-Xin;
Zhang, Qian;
Tang, Kin Fai;
Kaliaperumal, Nivashini;
Lim, Angeline Pei Chiew;
Hibberd, Martin L;
Chan, Soh Ha;
+6 more...Connolly, John E;
Krishnan, Manoj N;
Lok, Shee Mei;
Hanson, Brendon J;
Lin, Chao-Nan;
Ooi, Eng Eong;
(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. 2722-2727.
ISSN 0027-8424
DOI: https://doi.org/10.1073/pnas.1317454111
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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.