Species-specific impact of the autophagy machinery on Chikungunya virus infection

EMBO Rep. 2013 Jun;14(6):534-44. doi: 10.1038/embor.2013.51. Epub 2013 Apr 26.

Abstract

Chikungunya virus (CHIKV) is a recently re-emerged arbovirus that triggers autophagy. Here, we show that CHIKV interacts with components of the autophagy machinery during its replication cycle, inducing a cytoprotective effect. The autophagy receptor p62 protects cells from death by binding ubiquitinated capsid and targeting it to autophagolysosomes. By contrast, the human autophagy receptor NDP52--but not its mouse orthologue--interacts with the non-structural protein nsP2, thereby promoting viral replication. These results highlight the distinct roles of p62 and NDP52 in viral infection, and identify NDP52 as a cellular factor that accounts for CHIKV species specificity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Alphavirus Infections / virology*
  • Animals
  • Autophagy*
  • Capsid / metabolism
  • Chikungunya Fever
  • Chikungunya virus / physiology*
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Phagosomes / metabolism
  • Phagosomes / virology
  • Protein Binding
  • Protein Transport
  • Sequestosome-1 Protein
  • Sirolimus / pharmacology
  • Species Specificity
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication*

Substances

  • Adaptor Proteins, Signal Transducing
  • CALCOCO2 protein, human
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Viral Nonstructural Proteins
  • light chain 3, human
  • Sirolimus