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Journal of Virology, December 2004, p. 13132-13138, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13132-13138.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

JNK Regulates the Release of Proapoptotic Mitochondrial Factors in Reovirus-Infected Cells

Penny Clarke,1* Suzanne M. Meintzer,1 Yibing Wang,2 Lisa A. Moffitt,2 Sarah M. Richardson-Burns,3 Gary L. Johnson,4 and Kenneth L. Tyler1,2,5,6

Departments of Neurology,1 Immunology,2 Neuroscience,3 Medicine and Microbiology, University of Colorado Health Sciences Center,5 Denver Veteran's Affairs Medical Center, Denver, Colorado,6 Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina4

Received 25 March 2004/ Accepted 19 July 2004

Reovirus-induced apoptosis is associated with activation of the proapoptotic mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) and the JNK-associated transcription factor c-Jun. Here we show that reovirus-induced apoptosis and activation of caspase 3 are inhibited in cells deficient in MEK kinase 1, an upstream activator of JNK in reovirus-infected cells. Inhibition of JNK activity following reovirus infection delays the release of proapoptotic mitochondrial factors and the subsequent onset of apoptosis. In contrast, reovirus-induced apoptosis is not blocked by infection with adenovirus expressing dominant-negative c-Jun, and c-Jun activation does not correlate with apoptosis in reovirus-infected cells. This is the first report demonstrating that JNK is associated with regulation of mitochondrial pathways of apoptosis following viral infection.

* Corresponding author. Mailing address: Dept. of Neurology (B 182), University of Colorado Health Sciences Center, 4200 East 9th Ave., Denver, CO 80262. Phone: (303) 393-3684. Fax: (303) 393-4686. E-mail: penny.clarke{at}uchsc.edu.

Journal of Virology, December 2004, p. 13132-13138, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13132-13138.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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