Leukocyte immunoglobulin-like receptor B1 is critical for antibody-dependent dengue
Abstract
Dengue virus (DENV) infects almost 400 million people annually and some of these infections result in life threatening disease. An incomplete understanding of pathogenesis, particularly on how non- or subneutralizing levels of antibody augments DENV infection of cells expressing Fc-gamma receptors (FcγRs), has hampered vaccine development. Here, we show that, to overcome the activating FcγR-dependent expression of type-I interferon stimulated genes (ISGs), DENV binds and activates the inhibitory receptor, leukocyte immunoglobulin-like receptor-B1 (LILRB1). LILRB1 signals through its immunoreceptor tyrosine-based inhibition motif cytoplasmic tail to inhibit the expression of ISGs required for successful antibody-dependent DENV infection. Inhibition of DENV activation of LILRB1 could hence be a strategy for vaccine or therapeutic design.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- February 2014
- DOI:
- 10.1073/pnas.1317454111
- Bibcode:
- 2014PNAS..111.2722C