Ectromelia Virus Affects Mitochondrial Network Morphology, Distribution, and Physiology in Murine Fibroblasts and Macrophage Cell Line

Viruses. 2018 May 16;10(5):266. doi: 10.3390/v10050266.


Mitochondria are multifunctional organelles that participate in numerous processes in response to viral infection, but they are also a target for viruses. The aim of this study was to define subcellular events leading to alterations in mitochondrial morphology and function during infection with ectromelia virus (ECTV). We used two different cell lines and a combination of immunofluorescence techniques, confocal and electron microscopy, and flow cytometry to address subcellular changes following infection. Early in infection of L929 fibroblasts and RAW 264.7 macrophages, mitochondria gathered around viral factories. Later, the mitochondrial network became fragmented, forming punctate mitochondria that co-localized with the progeny virions. ECTV-co-localized mitochondria associated with the cytoskeleton components. Mitochondrial membrane potential, mitochondrial fission⁻fusion, mitochondrial mass, and generation of reactive oxygen species (ROS) were severely altered later in ECTV infection leading to damage of mitochondria. These results suggest an important role of mitochondria in supplying energy for virus replication and morphogenesis. Presumably, mitochondria participate in transport of viral particles inside and outside of the cell and/or they are a source of membranes for viral envelope formation. We speculate that the observed changes in the mitochondrial network organization and physiology in ECTV-infected cells provide suitable conditions for viral replication and morphogenesis.

Keywords: ectromelia virus; mitochondrial mass; mitochondrial membrane potential; mitochondrial network; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / physiology
  • Dynamins / metabolism
  • Ectromelia virus / physiology*
  • Ectromelia virus / ultrastructure
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibroblasts / virology*
  • GTP Phosphohydrolases / metabolism
  • L Cells
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Macrophages / virology*
  • Membrane Potential, Mitochondrial / physiology
  • Mice
  • Microtubule-Organizing Center / metabolism
  • Microtubule-Organizing Center / virology
  • Mitochondria / metabolism
  • Mitochondria / physiology*
  • Mitochondria / ultrastructure*
  • Mitochondria / virology
  • Mitochondrial Proteins / metabolism
  • RAW 264.7 Cells
  • Reactive Oxygen Species / analysis
  • Tubulin / metabolism
  • Virion / metabolism
  • Virus Replication


  • FIS1 protein, mouse
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Tubulin
  • GTP Phosphohydrolases
  • Opa1 protein, mouse
  • Dnm1l protein, mouse
  • Dynamins