The involvement of a stress-activated pathway in equine influenza virus-mediated apoptosis

Lin, CB Zimmer, SG Lu, ZJ Holland, RE Dong, Q Chambers, TM

Cb. Lin et al., The involvement of a stress-activated pathway in equine influenza virus-mediated apoptosis, VIROLOGY, 287(1), 2001, pp. 202-213

69

INGLESE

Article

Microbiology

VIROLOGY

0042-6822 → ACNP

287

1

2001

202 - 213

ISI

0042-6822(20010815)287:1<202:TIOASP>2.0.ZU;2-A

We have shown elsewhere that equine-2 influenza virus (EIV; subtype H3N8) i nduced pronounced cell death in infected cells through apoptosis as demonst rated by DNA fragmentation assay and a combined TUNEL and immunostaining sc heme. In this study, we investigated the mechanism of EM-mediated cytotoxic ity on a permissive mammalian epithelial cell line, Madin-Darby canine kidn ey (MDCK) cells. EIV infection increased the cellular levels of oxidative s tress and c-Jun/AP-1 protein (which is known to be affected by oxidative st ress), as well as its DNA binding activity. Increased production of TGF-bet a1, an inducer of c-Jun N-terminal kinase or stress-activated protein kinas e (JNK/SAPK) activation, was also detected in EIV-infected MDCK cells. It h as been reported that TGF-beta may initiate a signaling cascade leading to JNK/SAPK activation. Addition of c-Jun antisense oligodeoxynucleotide, anti oxidant N-acetyl-cysteine (NAC), JNK/SAPK inhibitor carvedilol, or TGF-beta -neutralizing antibody effectively blocked cJun/AP-1 upregulation and TGF- beta1 production mediated by EIV Infection. These treatments also attenuate d EIV-induced cytopathogenic effects (CPE) and apoptosis. Our results sugge st that a stress-activated pathway is involved in apoptosis mediated by EIV infection. It is likely that EIV infection turns on the JNK/SAPK cascade, which modulates the activity of apoptosis-promoting regulatory factor c-Jun /AP-1 and epithelial growth inhibitory cytokine TGF-beta. (C) 2001 Academic Press.