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J Virol, June 1998, p. 4918-4924, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Transmissible Gastroenteritis Coronavirus Induces Programmed Cell Death in Infected Cells through a Caspase-Dependent Pathway

Jean-François Eleouet,* Stefan Chilmonczyk, Lydia Besnardeau, and Hubert Laude

Unité de Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France

Received 15 October 1997/Accepted 16 March 1998

In this report, we show that apoptosis (or programmed cell death) is induced in different cell lines infected with a coronavirus, the porcine transmissible gastroenteritis virus (TGEV). Kinetic analysis of internucleosomal DNA cleavage by agarose gel electrophoresis and flow cytometry or cytometric monitoring of the mitochondrial transmembrane potential showed that, for ST cells infected with TGEV, the first overt signs of apoptosis appeared from 10 to 12 h postinfection on. They preceded 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-fluoromethylketone blocked TGEV-induced apoptosis with no effect on virus production. The thiol agent pyrrolidine dithiocarbamate inhibited apoptosis, suggesting that TGEV infection may lead to apoptosis via cellular oxidative stress. The effect of TGEV infection on activation of NF-kappa B, a transcription factor known to be activated by oxidative stress, was examined. NF-kappa B DNA binding was shown to be strongly and quickly induced by TGEV infection. However, transcription factor decoy experiments showed that NF-kappa B activation is not critical for TGEV-induced apoptosis.


* Corresponding author. Mailing address: INRA, Unité de Virologie et Immunologie Moléculaires, 78352 Jouy-en-Josas cedex, France. Phone: (33) 1 34 65 26 41. Fax: (33) 1 34 65 26 21. E-mail: eleouet{at}biotec.jouy.inra.fr.


J Virol, June 1998, p. 4918-4924, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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