Murine coronavirus-induced oligodendrocyte apoptosis is mediated through the activation of the Fas signaling pathway

Virology. 2007 Apr 10;360(2):364-75. doi: 10.1016/j.virol.2006.10.044. Epub 2006 Dec 6.


We previously showed that infection of rat oligodendrocytes by ultraviolet light-inactivated mouse hepatitis virus (MHV) resulted in apoptosis, suggesting that the apoptosis is triggered during cell entry. To further characterize the earliest apoptotic signaling events, here we treated cells with an antibody specific to the MHV receptor prior to and during virus infection or with an antibody specific to MHV spike protein following virus binding. Both treatments blocked virus infection and apoptosis, indicating that virus-receptor binding is necessary but not sufficient for the apoptosis induction. Furthermore, virus infection significantly increased the formation of the "death-receptor complexes" consisting of Fas, Fas-associated death domain and procaspase-8, but did not induce the complexes involving the tumor necrosis factor receptor and its associated death domain, demonstrating the specific activation of the Fas signaling pathway. Moreover, virus infection did not alter the abundance of the individual proteins of the complexes, suggesting that the activation of the Fas signaling pathway was at the post-translational level. Treatment with a Fas/Fc chimera, which blocks Fas-Fas ligand-mediated apoptosis, inhibited the formation of the complexes and blocked the activation of caspase-8 and apoptosis in MHV-infected cells. It also inhibited the release of cytochrome c from mitochondria and the activation of caspase-9. These results demonstrate that oligodendrocyte apoptosis is triggered by MHV infection during cell entry through the activation of the Fas signaling pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis*
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Cell Line
  • Cytochromes c / metabolism
  • Cytoplasm / metabolism
  • Fas-Associated Death Domain Protein / metabolism
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / metabolism
  • Mice
  • Models, Biological
  • Murine hepatitis virus / immunology
  • Murine hepatitis virus / physiology*
  • Oligodendroglia / cytology*
  • Oligodendroglia / metabolism
  • Oligodendroglia / virology*
  • Rats
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Virus / antagonists & inhibitors
  • Receptors, Virus / metabolism
  • Signal Transduction*
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / antagonists & inhibitors
  • Viral Envelope Proteins / metabolism
  • Virus Attachment
  • fas Receptor / metabolism*


  • Fas protein, mouse
  • Fas-Associated Death Domain Protein
  • Membrane Glycoproteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • fas Receptor
  • Cytochromes c
  • Caspase 8
  • Caspase 9