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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody-Dependent Enhancement / immunology
  • Antibody-Dependent Enhancement / physiology*
  • Antigens, CD / metabolism*
  • Blotting, Western
  • Cell Line
  • Dengue / immunology
  • Dengue / physiopathology*
  • Dengue Virus / metabolism*
  • Dengue Virus / physiology
  • Humans
  • Leukocyte Immunoglobulin-like Receptor B1
  • Microarray Analysis
  • RNA, Small Interfering / genetics
  • Receptors, IgG / metabolism
  • Receptors, Immunologic / metabolism*


  • Antigens, CD
  • LILRB1 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • RNA, Small Interfering
  • Receptors, IgG
  • Receptors, Immunologic