Caspase 3 activation during herpes simplex virus 1 infection.
During herpes simplex virus 1 (HSV-1) infection, apoptosis is initiated by immediate early gene transcription and is later modulated by proteins synthesized in infected cells. We have previously shown that procaspase 3 levels are reduced during HSV-1 replication. We now demonstrate that a replication-defective HSV-1 recombinant virus which is incapable of packaging viral DNA into capsids activated caspase 3 but retained the ability to prevent the apoptotic process from killing the infected cells. This implies that HSV-1-dependent apoptosis is not merely a response to abortive infection. Maximum accumulation of the active form of caspase 3 accompanied complete HSV-1-dependent apoptosis. Additionally, caspase 7 was found to be activated during HSV-1-dependent apoptosis. Infected MCF-7 cells which ectopically express caspase 3 underwent more efficient apoptosis than their caspase 3-null parental counterparts, confirming that caspase 3 contributes to HSV-1-dependent apoptosis. However, caspase 3 reconstitution did not make the MCF-7 cells as sensitive as HEp-2 cells to HSV-1-dependent apoptosis, suggesting that other cellular factors may be involved in conferring resistance to this process. These results indicate that caspase 3 activation is a consequence of HSV-1 infection and have important implications in our understanding of the interactions of the virus with host cells.
Kraft
Rachel M
RM
Department of Microbiology, One Gustave L. Levy Place, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Nguyen
Marie L
ML
Yang
Xiao-He
XH
Thor
Ann D
AD
Blaho
John A
JA
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004792:Enzyme Precursors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006561:Herpes Simplex / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D014709:Vero Cells; D019065:Virus Assembly
D004792:Enzyme Precursors; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases