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The HPV E7 oncoprotein inhibits tumor necrosis factor alpha-mediated apoptosis in normal human fibroblasts

D A Thompson1, V Zacny, G S Belinsky

  • 1Department of Pathology and Harvard Center for Cancer Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, MA 02115, USA.

Oncogene
|July 6, 2001
PubMed

Insights

Human papillomavirus type 16 E7 oncoprotein hinders tumor necrosis factor-alpha (TNF)-induced apoptosis by blocking pro-caspase 8 activation. E7-expressing cells show resistance to TNF and Fas-mediated cell death.

Area of Science:

  • Cell Biology
  • Virology
  • Immunology

Background:

  • Cytokines like tumor necrosis factor-alpha (TNF) induce apoptosis, a crucial defense against viral infections.
  • Viruses often develop strategies to evade host apoptosis mechanisms, promoting their survival.
  • The human papillomavirus type 16 E7 oncoprotein is implicated in cellular transformation and immune evasion.

Purpose of the Study:

  • To investigate the effect of human papillomavirus type 16 E7 oncoprotein on TNF-mediated apoptosis in normal human diploid fibroblasts.
  • To determine the specific molecular mechanisms by which E7 influences apoptosis signaling pathways.

Main Methods:

  • Culturing normal human diploid fibroblasts expressing the HPV16 E7 oncoprotein.
  • Treating cells with TNF and Fas receptor agonists to induce apoptosis.
  • Analyzing pro-caspase 8 activation and overall apoptotic response.

Main Results:

  • Fibroblasts expressing HPV16 E7 demonstrated reduced apoptosis upon TNF treatment.
  • E7 expression impaired pro-caspase 8 activation, a key step in TNF-mediated apoptosis.
  • E7 conferred partial resistance to Fas-induced apoptosis, with slower induction rates.

Conclusions:

  • The HPV16 E7 oncoprotein specifically obstructs cytokine-mediated activation of pro-caspase 8.
  • E7 expression in fibroblasts leads to a defect in initiating apoptosis, contributing to cellular transformation and viral persistence.

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