Dengue virus compartmentalization during antibody-enhanced infection

Sci Rep. 2017 Jan 13:7:40923. doi: 10.1038/srep40923.

Abstract

Secondary infection with a heterologous dengue virus (DENV) serotype increases the risk of severe dengue, through a process termed antibody-dependent enhancement (ADE). During ADE, DENV is opsonized with non- or sub-neutralizing antibody levels that augment entry into monocytes and dendritic cells through Fc-gamma receptors (FcγRs). We previously reported that co-ligation of leukocyte immunoglobulin-like receptor-B1 (LILRB1) by antibody-opsonized DENV led to recruitment of SH2 domain-containing phosphatase-1 (SHP-1) to dephosphorylate spleen tyrosine kinase (Syk) and reduce interferon stimulated gene induction. Here, we show that LILRB1 also signals through SHP-1 to attenuate the otherwise rapid acidification for lysosomal enzyme activation following FcγR-mediated uptake of DENV. Reduced or slower trafficking of antibody-opsonized DENV to lytic phagolysosomal compartments, demonstrates how co-ligation of LILRB1 also permits DENV to overcome a cell-autonomous immune response, enhancing intracellular survival of DENV. Our findings provide insights on how antiviral drugs that modify phagosome acidification should be used for viruses such as DENV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody-Dependent Enhancement*
  • Antigens, CD / metabolism
  • Cell Line, Tumor
  • Dengue / immunology*
  • Dengue Virus / immunology*
  • Dengue Virus / physiology
  • Humans
  • Leukocyte Immunoglobulin-like Receptor B1 / metabolism
  • Phagosomes / immunology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • Virus Internalization

Substances

  • Antigens, CD
  • LILRB1 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6