Dengue Virus Perturbs Mitochondrial Morphodynamics to Dampen Innate Immune Responses

Cell Host Microbe. 2016 Sep 14;20(3):342-356. doi: 10.1016/j.chom.2016.07.008. Epub 2016 Aug 18.


With no antiviral drugs or widely available vaccines, Dengue virus (DENV) constitutes a public health concern. DENV replicates at ER-derived cytoplasmic structures that include substructures called convoluted membranes (CMs); however, the purpose of these membrane alterations remains unclear. We determine that DENV nonstructural protein (NS)4B, a promising drug target with unknown function, associates with mitochondrial proteins and alters mitochondria morphology to promote infection. During infection, NS4B induces elongation of mitochondria, which physically contact CMs. This restructuring compromises the integrity of mitochondria-associated membranes, sites of ER-mitochondria interface critical for innate immune signaling. The spatio-temporal parameters of CM biogenesis and mitochondria elongation are linked to loss of activation of the fission factor Dynamin-Related Protein-1. Mitochondria elongation promotes DENV replication and alleviates RIG-I-dependent activation of interferon responses. As Zika virus infection induces similar mitochondria elongation, this perturbation may protect DENV and related viruses from innate immunity and create a favorable replicative environment.

MeSH terms

  • Dengue Virus / pathogenicity*
  • Dynamins
  • GTP Phosphohydrolases / antagonists & inhibitors*
  • Host-Pathogen Interactions*
  • Immune Evasion*
  • Immunity, Innate*
  • Microscopy, Electron, Transmission
  • Microtubule-Associated Proteins / antagonists & inhibitors*
  • Mitochondria / ultrastructure*
  • Mitochondrial Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / metabolism*


  • Microtubule-Associated Proteins
  • Mitochondrial Proteins
  • NS4B protein, flavivirus
  • Viral Nonstructural Proteins
  • GTP Phosphohydrolases
  • DNM1L protein, human
  • Dynamins