Adeno-associated virus induces apoptosis during coinfection with adenovirus

Jennifer M Timpe1, Kristin C Verrill, Bret N Black

  • 1Department of Biochemistry and Cancer Biology, Medical University of Ohio, 3035 Arlington Ave., Toledo, OH 43614-5804, USA.

Virology
|October 3, 2006
PubMed

Insights

Adeno-associated virus (AAV) induces programmed cell death (apoptosis) during viral infections. This cell death is caspase-dependent and independent, even when cells are coinfected with adenovirus (Ad).

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Adeno-associated virus (AAV) is a nonpathogenic parvovirus requiring helper adenovirus (Ad) for replication.
  • Adenovirus (Ad) infection induces programmed cell death (apoptosis), complicating the study of AAV-induced apoptosis.
  • Adenoviral death protein (ADP) plays a role in Ad-mediated cytolysis.

Purpose of the Study:

  • To investigate whether AAV infection induces apoptosis during viral coinfection.
  • To differentiate AAV-induced apoptosis from Ad-mediated cell death.
  • To elucidate the mechanisms of AAV-induced cell death.

Main Methods:

  • Coinfection of cells with AAV and an E3 adenoviral death protein (ADP) mutant (pm534) or wild-type Ad.
  • Assessment of cell killing, cytolysis, and apoptosis using biochemical and morphological criteria.
  • Measurement of caspase activation and extracellular pH.

Main Results:

  • AAV coinfection with pm534 or wild-type Ad resulted in increased cell killing compared to Ad alone.
  • AAV and Ad coinfection showed moderate caspase activation, unlike infections with Ad alone.
  • AAV coinfection led to increased extracellular pH and exhibited characteristics of both caspase-dependent and independent apoptosis.

Conclusions:

  • Adeno-associated virus (AAV) induces apoptosis during viral infections, independent of helper adenovirus (Ad).
  • AAV-induced apoptosis involves both caspase-dependent and caspase-independent pathways.
  • AAV coinfection modulates cellular processes, including pH, contributing to programmed cell death.

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