The Vici syndrome protein EPG5 regulates intracellular nucleic acid trafficking linking autophagy to innate and adaptive immunity

Autophagy. 2018;14(1):22-37. doi: 10.1080/15548627.2017.1389356. Epub 2018 Jan 2.


Vici syndrome is a human inherited multi-system disorder caused by recessive mutations in EPG5, encoding the EPG5 protein that mediates the fusion of autophagosomes with lysosomes. Immunodeficiency characterized by lack of memory B cells and increased susceptibility to infection is an integral part of the condition, but the role of EPG5 in the immune system remains unknown. Here we show that EPG5 is indispensable for the transport of the TLR9 ligand CpG to the late endosomal-lysosomal compartment, and for TLR9-initiated signaling, a step essential for the survival of human memory B cells and their ultimate differentiation into plasma cells. Moreover, the predicted structure of EPG5 includes a membrane remodeling domain and a karyopherin-like domain, thus explaining its function as a carrier between separate vesicular compartments. Our findings indicate that EPG5, by controlling nucleic acids intracellular trafficking, links macroautophagy/autophagy to innate and adaptive immunity.

Keywords: EPG5; Endosomal trafficking; TLR9; Vici syndrome; memory B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Agenesis of Corpus Callosum / genetics
  • Agenesis of Corpus Callosum / immunology
  • Autophagy / immunology*
  • Autophagy-Related Proteins
  • B-Lymphocytes / immunology
  • Biological Transport
  • Cataract / genetics
  • Cataract / immunology
  • Cell Line
  • DNA / metabolism*
  • Endosomes / metabolism*
  • Humans
  • Immunity, Innate*
  • Lysosomal Membrane Proteins
  • Lysosomes / metabolism*
  • Mutation
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA / metabolism*
  • Toll-Like Receptor 9 / metabolism
  • Vesicular Transport Proteins


  • Autophagy-Related Proteins
  • EPG5 protein, human
  • Lysosomal Membrane Proteins
  • Proteins
  • Toll-Like Receptor 9
  • Vesicular Transport Proteins
  • RNA
  • DNA

Supplementary concepts

  • Absent corpus callosum cataract immunodeficiency