Adeno-associated virus induces apoptosis during coinfection with adenovirus

Jennifer M. Timpe, Kristin C. Verrill, Bret N. Black, Han Fei Ding, James P. Trempe

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Adeno-associated virus (AAV) is a nonpathogenic parvovirus that efficiently replicates in the presence of adenovirus (Ad). Exogenous expression of the AAV replication proteins induces caspase-dependent apoptosis, but determining if AAV infection causes apoptosis during viral infection is complicated by Ad-mediated programmed cell death. To eliminate Ad-induced cytolysis, we used an E3 adenoviral death protein (ADP) mutant, pm534. AAV and pm534-coinfected cells exhibited increased cell killing compared to pm534 alone. Relative to cells infected with Ad alone, AAV and wild-type Ad-infected cells displayed decreased ADP expression, increased cytolysis until the third day of the infection, and decreased cytolysis thereafter. Biochemical and morphological characteristics of apoptosis were observed during coinfections with AAV and pm534 or Ad, including a moderate degree of caspase activation that was not present during infections with pm534 or Ad alone. AAV coinfection also increased extracellular pH. These studies suggest that AAV induces caspase-dependent and caspase-independent apoptosis.

Original languageEnglish (US)
Pages (from-to)391-401
Number of pages11
JournalVirology
Volume358
Issue number2
DOIs
StatePublished - Feb 20 2007
Externally publishedYes

Keywords

  • AAV-induced apoptosis

ASJC Scopus subject areas

  • Virology

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