Adeno-associated virus induces apoptosis during coinfection with adenovirus.
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.
Timpe
Jennifer M
JM
Department of Biochemistry and Cancer Biology, Medical University of Ohio, 3035 Arlington Ave., Toledo, OH 43614-5804, USA.
Verrill
Kristin C
KC
Black
Bret N
BN
Ding
Han-Fei
HF
Trempe
James P
JP
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D017503:Adenovirus E3 Proteins / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D003588:Cytopathogenic Effect, Viral; D000229:Dependovirus / Q000472:pathogenicity / Q000502:physiology*; D006378:Helper Viruses / Q000502:physiology*; D006801:Humans; D010322:Parvoviridae Infections / Q000503:physiopathology*; D017354:Point Mutation; D014774:Virulence; D014779:Virus Replication
D017503:Adenovirus E3 Proteins; D020169:Caspases