Caspase 3 activation is essential for efficient influenza virus propagation.
Apoptosis is a hallmark event observed upon infection with many viral pathogens, including influenza A virus. The apoptotic process is executed by a proteolytic system consisting of a family of cysteinyl proteases, termed caspases. Since the consequences of apoptosis induction and caspase activation for the outcome of an influenza virus infection are not clear, we have addressed this issue by interfering with expression or function of a major virus-induced apoptosis effector, caspase 3. Surprisingly, influenza virus propagation was strongly impaired in the presence of an inhibitor that blocks caspase 3 and in cells where caspase 3 was partially knocked down by small interfering RNAs. Consistent with these findings, poor replication efficiencies of influenza A viruses in cells deficient for caspase 3 could be boosted 30-fold by ectopic expression of the protein. Mechanistically, the block in virus propagation appeared to be due to retention of the viral RNP complexes in the nucleus, preventing formation of progeny virus particles. Our findings indicate that caspase 3 activation during the onset of apoptosis is a crucial event for efficient influenza virus propagation.
Wurzer
Walter J
WJ
Institute of Molecular Medicine (IMM), Heinrich-Heine Universität, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
Planz
Oliver
O
Ehrhardt
Christina
C
Giner
Martin
M
Silberzahn
Tobias
T
Pleschka
Stephan
S
Ludwig
Stephan
S
D000818:Animals; D001483:Base Sequence; D002070:Butadienes / Q000494:pharmacology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004789:Enzyme Activation; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014709:Vero Cells; D014779:Virus Replication / Q000502:physiology*; D051636:X-Linked Inhibitor of Apoptosis Protein
D002070:Butadienes; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D009570:Nitriles; D009842:Oligopeptides; D011506:Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C113580:U 0126; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases