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Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2722-7. doi: 10.1073/pnas.1317454111. Epub 2014 Jan 13.

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

Author information

1
Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169857.

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.

KEYWORDS:

early innate immune response; immune evasion; innate immune signaling

PMID:
24550301
PMCID:
PMC3932915
DOI:
10.1073/pnas.1317454111
[Indexed for MEDLINE]
Free PMC Article
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