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Interaction between endoplasmic reticulum stress and caspase 8 activation in retrovirus MoMuLV-ts1-infected

Na Liu1, Virginia L Scofield, Wenan Qiang

  • 1Department of Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park-Research Division, Smithville, 78957, USA.

Virology
|February 10, 2006
PubMed

Insights

Murine retrovirus infection triggers astrocyte apoptosis through endoplasmic reticulum (ER) stress and caspase 8 activation. Inhibiting caspase 8 reduces ER stress, revealing a link between these pathways in neuroinflammation.

Area of Science:

  • Neurovirology
  • Cellular Biology
  • Immunology

Background:

  • Murine retrovirus (MoMuLV-ts1) causes paralysis and immune deficiency in mice.
  • Previous work indicated MoMuLV-ts1 induces astrocyte apoptosis via endoplasmic reticulum (ER) and mitochondrial stress.

Purpose of the Study:

  • To elucidate the mechanisms of caspase 8 activation in ts1-infected astrocytes.
  • To investigate the interplay between ER stress and caspase 8-mediated apoptosis.

Main Methods:

  • Assessed caspase 8 activation in ts1-infected astrocytes.
  • Examined the role of death receptor DR5 and GADD153/CHOP in caspase 8 activation.
  • Utilized Z-IETD-FMK, a caspase 8 inhibitor, to evaluate its effects on ER stress and BAP31 cleavage.

Main Results:

  • Caspase 8 activation was mediated by ER stress-induced DR5 and GADD153/CHOP, not TNFalpha/TNF-R1.
  • Inhibition of caspase 8 by Z-IETD-FMK reduced ER stress.
  • Z-IETD-FMK prevented BAP31 cleavage to BAP20, mitigating ER stress exacerbation.

Conclusions:

  • Caspase 8 activation in ts1-infected astrocytes is linked to ER stress.
  • ER stress-associated apoptotic pathways and caspase 8 signaling are interconnected.
  • Targeting caspase 8 may offer a therapeutic strategy for retroviral-induced neuroinflammation.

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