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Human adenovirus type 5 induces cell lysis through autophagy and autophagy-triggered caspase activity

Hong Jiang1, Erin J White, Christian I Ríos-Vicil

  • 1Department of Neuro-Oncology, Unit 1002, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. hjiang@mdanderson.org

Journal of Virology
|March 4, 2011
PubMed

Insights

Oncolytic adenoviruses induce cell lysis through autophagy, a process involving autophagosomes and lysosomes. Inhibiting autophagy genes protects cells, suggesting autophagy modulation enhances oncolytic virus therapy for brain tumors.

Area of Science:

  • Oncology
  • Virology
  • Cell Biology

Background:

  • Oncolytic adenoviruses show promise for brain tumor treatment.
  • Increasing adenovirus-induced cell lysis is key to enhancing therapeutic efficacy.
  • The precise mechanism of adenovirus-induced cell lysis remains unclear.

Purpose of the Study:

  • To elucidate the role of autophagy in adenovirus-induced cell lysis.
  • To investigate the involvement of caspase activation in this process.
  • To explore autophagy modulation as a strategy for improving oncolytic adenovirus therapy.

Main Methods:

  • Studied the effects of adenovirus infection on cell structure and autophagy.
  • Analyzed autophagic vacuoles and autophagosome-lysosome fusion post-infection.
  • Investigated the impact of downregulating autophagy genes (ATG5, ATG10) on cell lysis.
  • Examined the role of autophagy in triggering caspase activity via the FADD/caspase 8 pathway.

Main Results:

  • Autophagy, marked by numerous autophagic vacuoles, accompanies adenovirus-induced cell lysis.
  • The complete autophagic process, from initiation to lysosomal turnover, is induced by the virus.
  • Formation of autophagosomes alone is sufficient for viral cell lysis.
  • Downregulating ATG5 or ATG10 significantly rescued infected cells from lysis.
  • Autophagy activation of caspase activity through the FADD/caspase 8 pathway contributes to cell lysis.

Conclusions:

  • Autophagy is a critical component of adenovirus-induced cell lysis.
  • Caspase activation, triggered by autophagy, also contributes to viral cell lysis.
  • Targeting autophagy and caspase pathways offers a potential strategy to enhance oncolytic adenovirus efficacy in brain tumors.

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