TRANSMISSIBLE GASTROENTERITIS CORONAVIRUS INDUCES PROGRAMMED CELL-DEATH IN INFECTED-CELLS THROUGH A CASPASE-DEPENDENT PATHWAY

In this report, we show that apoptosis (or programmed cell death) is i nduced in different cell lines infected with a coronavirus, the porcin e transmissible gastroenteritis virus (TGEV), Kinetic analysis of inte rnucleosomal DNA cleavage by agarose gel electrophoresis and flow cyto metry or cytometric monitoring of the mitochondrial transmembrane pote ntial showed that, for ST cells infected with TGEV, the first overt si gns of apoptosis appeared from 10 to 12 h postinfection on, They prece ded morphological changes characteristic of cells undergoing apoptosis , as observed by light and electron microscopy, The tripeptide pan-ICE (caspase) inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketon e blocked TGEV-induced apoptosis with no effect on virus production. T he thiol agent pyrrolidine dithiocarbamate inhibited apoptosis, sugges ting that TGEV infection may lead to apoptosis via cellular oxidative stress. The effect of TGEV infection on activation of NF-kappa B, a tr anscription factor known to be activated by oxidative stress, was exam ined, NF-kappa B DNA binding was shown to be strongly and quickly indu ced by TGEV infection. However, transcription factor decoy experiments showed that NF-kappa B activation is not critical for TGEV-induced ap optosis.