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The ability of BHRF1 to inhibit apoptosis is dependent on stimulus and cell type

L Foghsgaard1, M Jäättelä

  • 1Division for Cancer Biology, Danish Cancer Society, Copenhagen.

Journal of Virology
|October 6, 1997
PubMed

Insights

Epstein-Barr virus (EBV) protein BHRF1 protects cells from apoptosis, similar to Bcl-2. This anti-apoptosis function is cell-type specific and depends on the trigger, potentially aiding virus production.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Cellular apoptosis, triggered by mechanisms like tumor necrosis factor (TNF) and Fas, is a key host defense against transformed or infected cells.
  • Resistance to apoptosis can contribute to disease development.
  • Identifying genes that confer resistance to apoptosis is crucial for understanding disease pathogenesis.

Purpose of the Study:

  • To identify genes that protect cells from apoptosis.
  • To characterize the anti-apoptotic function of the Epstein-Barr virus (EBV) protein BHRF1.

Main Methods:

  • Expression cloning strategy to identify apoptosis-protective genes.
  • Introduction of BHRF1 into MCF-Fas cells to assess its effect on apoptosis.
  • Comparison of BHRF1's function with Bcl-2 and Bcl-xL.
  • Analysis of BHRF1's mechanism of action on apoptosis-related enzymes and transcription factors.
  • Testing BHRF1 and Bcl-2 in BJAB B-cell lines.

Main Results:

  • BHRF1, an EBV early-lytic-cycle protein, was identified as an anti-apoptosis protein with homology to Bcl-2.
  • BHRF1 conferred significant resistance to TNF- and Fas-mediated apoptosis in MCF-Fas cells.
  • BHRF1's protective effects mirrored those of Bcl-2 and Bcl-xL, inhibiting caspase-3/CPP32 and cytosolic phospholipase A2 activation.
  • BHRF1's protective role was cell-type specific and stimulus-dependent, as it failed to protect BJAB cells from anti-Fas-induced apoptosis.

Conclusions:

  • BHRF1 acts as an anti-apoptosis protein, potentially protecting EBV-infected cells from host immune responses to facilitate viral production.
  • The anti-apoptotic function of BHRF1 is analogous to Bcl-2, exhibiting cell type specificity and dependence on the apoptotic stimulus.
  • Understanding BHRF1's role in apoptosis provides insights into viral pathogenesis and host-virus interactions.

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