The involvement of survival signaling pathways in rubella-virus induced apoptosis.
Rubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the development of such defects. Often the outcome of apoptotic stimuli is dependent on apoptotic, proliferative and survival signaling mechanisms in the cell. Therefore we investigated the role of phosphoinositide 3-kinase (PI3K)-Akt survival signaling and Ras-Raf-MEK-ERK proliferative signaling during RV-induced apoptosis in RK13 cells. Increasing levels of phosphorylated ERK, Akt and GSK3beta were detected from 24-96 hours post-infection, concomitant with RV-induced apoptotic signals. Inhibition of PI3K-Akt signaling reduced cell viability, and increased the speed and magnitude of RV-induced apoptosis, suggesting that this pathway contributes to cell survival during RV infection. In contrast, inhibition of the Ras-Raf-MEK-ERK pathway impaired RV replication and growth and reduced RV-induced apoptosis, suggesting that the normal cellular growth is required for efficient virus production.
Cooray
Samantha
S
Enteric, Neurological, and Respiratory Virus Laboratory, Health Protection Agency, 61 Colindale Avenue, London NW9 5HT, UK. s.cooray@imperial.ac.uk
Jin
Li
L
Best
Jennifer M
JM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011817:Rabbits; D012412:Rubella virus / Q000378:metabolism*; D015398:Signal Transduction; D014779:Virus Replication
D002070:Butadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D009570:Nitriles; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one