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STAT3 activates the anti-apoptotic form of caspase 9 in oncovirus-infected B lymphocytes

Siva Koganti1, Sandeepta Burgula1, Sumita Bhaduri-McIntosh2

  • 1Division of Infectious Diseases, Department of Pediatrics, Stony Brook University, NY, USA.

Virology
|January 14, 2020
PubMed

Insights

Epstein-Barr virus (EBV) hijacks STAT3 to activate caspase 9, which then activates caspase 7. This process impairs DNA repair, allowing EBV-infected cells to survive and proliferate.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Epstein-Barr virus (EBV) is a human oncogenic virus that infects B-lymphocytes.
  • EBV infection leads to the activation of the STAT3 transcription factor.
  • STAT3 activation is implicated in viral-induced cell proliferation and evasion of DNA damage responses.

Purpose of the Study:

  • To elucidate the precise mechanism by which EBV-infected B-cells activate caspase 7.
  • To investigate the role of STAT3 and caspase 9 in EBV-mediated cellular processes.
  • To understand how EBV-infected cells overcome DNA replication stress and maintain proliferation.

Main Methods:

  • Analysis of caspase activation pathways in EBV-infected B-lymphocytes.
  • Investigation of STAT3-mediated transcriptional regulation of caspases.
  • Detection of caspase cleavage products and assessment of Chk1 phosphorylation.
  • Evaluation of caspase 9 splice variants in infected cells.

Main Results:

  • STAT3 transcriptionally activates caspase 9 in newly EBV-infected B-cells.
  • Caspase 9 subsequently activates caspase 7, leading to impaired Chk1 phosphorylation at S345.
  • EBV infection induces an increase in the dominant-negative splice variant of caspase 9.
  • STAT3 inhibition abrogates the expression of dominant-negative caspase 9.

Conclusions:

  • EBV utilizes STAT3 to activate caspase 9, which then activates caspase 7.
  • This pathway impairs ATR-Chk1 signaling, allowing EBV-transformed cells to proliferate despite DNA damage.
  • EBV balances caspase 9 activation with the expression of its dominant-negative form to promote cell survival and viral replication.
Keywords:
B-lymphocytesCaspase 7Caspase 9Epstein-barr virusSTAT3

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