TY - JOUR
T1 - vFLIP protects PC-12 cells from apoptosis induced by Sindbis virus: implications for the role of TNF-α
AU - Sarid, R.
AU - Ben-Moshe, T
AU - Kazimirsky, G
AU - Weisberg, S
AU - Appel, E
AU - Kobiler, D
AU - Lustig, S
AU - Brodie, C
PY - 2001
Y1 - 2001
N2 - Sindbis virus (SV) is an alphavirus used as a model for studying the pathogenesis of viral encephalitis. In this study we examined the effects and the mechanisms involved in the apoptosis induced by SV in PC-12 cells, and the role of a vFLIP in this process. Infection of PC-12 cells with a neurovirulent strain of SV, SVNI, induced cell apoptosis. Overexpression of vFLIP encoded by the HHV-8 or treatment with a caspase-8 inhibitor inhibited cell apoptosis. SVNI induced an increase in the expression of tumor necrosis factor α (TNF-α), and pretreatment of the cells with an anti-TNF-α blocking antibody or with soluble TNF-α receptor abrogated the apoptotic effect of SVNI. Moreover, TNF-αR1 knockout mice were more resistant to the cytopathic effects of the virus as compared to control animals. Our results indicate that the apoptosis induced by SVNI is mediated by activation of caspase-8, and that TNF-α plays an important role in the apoptotic response.
AB - Sindbis virus (SV) is an alphavirus used as a model for studying the pathogenesis of viral encephalitis. In this study we examined the effects and the mechanisms involved in the apoptosis induced by SV in PC-12 cells, and the role of a vFLIP in this process. Infection of PC-12 cells with a neurovirulent strain of SV, SVNI, induced cell apoptosis. Overexpression of vFLIP encoded by the HHV-8 or treatment with a caspase-8 inhibitor inhibited cell apoptosis. SVNI induced an increase in the expression of tumor necrosis factor α (TNF-α), and pretreatment of the cells with an anti-TNF-α blocking antibody or with soluble TNF-α receptor abrogated the apoptotic effect of SVNI. Moreover, TNF-αR1 knockout mice were more resistant to the cytopathic effects of the virus as compared to control animals. Our results indicate that the apoptosis induced by SVNI is mediated by activation of caspase-8, and that TNF-α plays an important role in the apoptotic response.
UR - https://scholar.google.co.il/scholar?q=vFLIP+protects+PC-12+cells+from+apoptosis+induced+by+Sindbis+virus%3A+implications+for+the+role+of+TNF-alpha&btnG=&hl=en&as_sdt=0%2C5
M3 - Article
VL - 8
SP - 1224
EP - 1228
JO - Cell Death & Differentiation
JF - Cell Death & Differentiation
IS - 12
ER -