AZT inhibits Visna/maedi virus-induced apoptosis

V Bellet1, R Duval, S Delebassée

  • 1Faculté de Pharmacie, Laboratoire de Microbiologie, Limoges, France.

Archives of Virology
|March 3, 2004
PubMed

Insights

3' azido-2',3'-deoxythymidine (AZT) inhibits visna/maedi virus-induced apoptosis in sheep cells. AZT blocks all viral-induced apoptotic pathways, including caspase activation and AIF release.

Area of Science:

  • Neurovirology
  • Cellular and Molecular Biology
  • Immunology

Background:

  • Visna/maedi virus (VMV) causes encephalitis and demyelination in sheep.
  • VMV infection induces apoptosis in sheep choroid plexus cells (SCPC) through intrinsic and extrinsic pathways.
  • The anti-apoptotic effects of 3' azido-2',3'-deoxythymidine (AZT), an HIV-1 reverse transcriptase inhibitor, on retrovirus-induced apoptosis are unknown.

Purpose of the Study:

  • To investigate the broad-range effect of AZT on inhibiting VMV-induced apoptosis in SCPC.
  • To determine if AZT can block the different apoptotic pathways activated by VMV infection.

Main Methods:

  • Apoptosis detection using DAPI staining and DNA laddering.
  • Assessing caspase cascade inhibition via caspase activity assays (caspase-3, -8, -9) and in situ labeling (FITC-VAD-FMK).
  • Immunocytochemistry to detect apoptosis-inducing factor (AIF) release.

Main Results:

  • AZT treatment inhibited morphological changes and DNA fragmentation associated with apoptosis.
  • AZT significantly reduced caspase-3, -8, and -9 activities and blocked FITC-VAD-FMK labeling.
  • AZT inhibited the release of apoptosis-inducing factor (AIF) from SCPC during VMV infection.

Conclusions:

  • AZT exhibits broad-spectrum anti-apoptotic effects against VMV-induced cell death.
  • AZT effectively blocks both intrinsic and extrinsic apoptotic pathways, as well as AIF-mediated apoptosis.
  • These findings suggest AZT's potential in managing retroviral infections that trigger apoptosis.

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