Importance of Akt signaling pathway for apoptosis in SARS-CoV-infected Vero E6 cells.
Severe acute respiratory syndrome (SARS) is an acute respiratory tract infectious disease that is associated with a new coronavirus (SARS-CoV). Our recent study indicated that SARS-CoV infection induces activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway and the p38 MAPK inhibitor partially inhibited its cytopathic effect in Vero E6 cells. The results of the present study indicated that before cell death, Akt, which is an inhibitor of apoptosis, was also activated in response to viral replication. Phosphorylation of a serine residue on Akt was detected at least 8 h postinfection (hpi), which declined after 18 hpi. Thus, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in virus-infected Vero E6 cells. However, a threonine residue was not phosphorylated. A downstream target of Akt, glycogen synthase kinase 3beta (GSK-3beta), was slightly phosphorylated, indicating that the level of activation of Akt was very low. PKCzeta, which is downstream of the PI3K pathway, was also phosphorylated in virus-infected cells. These results suggested that weak activation of Akt cannot prevent apoptosis induced by SARS-CoV infection in Vero E6 cells.
Mizutani
Tetsuya
T
Special Pathogens Laboratory, Department of Virology 1, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan. tmizutan@nih.go.jp
Fukushi
Shuetsu
S
Saijo
Masayuki
M
Kurane
Ichiro
I
Morikawa
Shigeru
S
D000818:Animals; D017209:Apoptosis; D002522:Chlorocebus aethiops; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D045473:Severe acute respiratory syndrome-related coronavirus / Q000472:pathogenicity*; D015398:Signal Transduction; D014709:Vero Cells
D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human