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Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic signaling during Herpes simplex virus infection.

Abstract：

:Trichosanthin (TCS) is a type I ribosome-inactivating protein with wide spectrum of pharmacological activities. It inhibits human immunodeficiency virus type 1 (HIV-1) and Herpes simplex virus type 1 (HSV-1) replication but the mechanism is not clear. From a previous study, TCS was found to be more cytotoxic to HIV-1 infected cells than uninfected cells. Similar finding was confirmed with HSV-1 in the present study. TCS induced cell death in HEp-2 cells and the EC(50) was 24.64μg/mL. When the same experiment was performed in HSV-1 infected HEp-2 cells, the EC(50) decreased to 3.01μg/mL. TCS appeared to cause more death and apoptosis in viral infected cells. This study explored plausible mechanism with respect to the apoptosis signal pathways. In uninfected cells, TCS induced CD95 (Fas)-mediated and caspase-8-dependent type I apoptosis. When cells were infected with HSV-1, apoptosis induced by TCS clearly switched to a more potent type II pathway. This involved mitochondrial depolarization and caspase-9 activation. The major evidences arose from studying the individual signals of the two apoptosis pathways in infected and uninfected cells. In addition, over expression of Bcl-2, which mainly affected the type II pathway reduced TCS induced apoptosis mostly in infected cells. This further demonstrated that the type II pathway was operating in infected cells. The reason for the switching is not entirely clear but it is well known that viral infection affects signal pathways especially those related to apoptosis. In conclusion, TCS selectively induces more apoptosis in HSV-1 infected cells than uninfected cells. The consequence of infection switches the TCS-induced apoptosis pathway from a CD95 (Fas) dependent type I to a more potent type II pathway mediated by mitochondrial depolarization and caspase-9 activation.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

He D,Yau K,He X,Shi H,Zheng Y,Tam S

doi

10.1016/j.molimm.2011.06.217

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

2000-8

issue

15-16

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(11)00429-9

journal_volume

pub_type

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Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic signaling during Herpes simplex virus infection.