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Journal of Virology, December 2001, p. 11275-11283, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11275-11283.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Reovirus Infection Activates JNK and the JNK-Dependent Transcription Factor c-Jun

Penny Clarke,1 Suzanne M. Meintzer,1 Christian Widmann,2,dagger Gary L. Johnson,2 and Kenneth L. Tyler1,3,4,5,*

Departments of Neurology,1 Pharmacology,2 Medicine,3 and Microbiology and Immunology,4 University of Colorado Health Science Center, Denver, Colorado 80262, and Denver Veterans Affairs Medical Center, Denver, Colorado 802205

Received 6 April 2001/Accepted 22 August 2001

Viral infection often perturbs host cell signaling pathways including those involving mitogen-activated protein kinases (MAPKs). We now show that reovirus infection results in the selective activation of c-Jun N-terminal kinase (JNK). Reovirus-induced JNK activation is associated with an increase in the phosphorylation of the JNK-dependent transcription factor c-Jun. Reovirus serotype 3 prototype strains Abney (T3A) and Dearing (T3D) induce significantly more JNK activation and c-Jun phosphorylation than does the serotype 1 prototypic strain Lang (T1L). T3D and T3A also induce more apoptosis in infected cells than T1L, and there was a significant correlation between the ability of these viruses to phosphorylate c-Jun and induce apoptosis. However, reovirus-induced apoptosis, but not reovirus-induced c-Jun phosphorylation, is inhibited by blocking TRAIL/receptor binding, suggesting that apoptosis and c-Jun phosphorylation involve parallel rather than identical pathways. Strain-specific differences in JNK activation are determined by the reovirus S1 and M2 gene segments, which encode viral outer capsid proteins (sigma 1 and µ1c) involved in receptor binding and host cell membrane penetration. These same gene segments also determine differences in the capacity of reovirus strains to induce apoptosis, and again a significant correlation between the capacity of T1L × T3D reassortant reoviruses to both activate JNK and phosphorylate c-Jun and to induce apoptosis was shown. The extracellular signal-related kinase (ERK) is also activated in a strain-specific manner following reovirus infection. Unlike JNK activation, ERK activation could not be mapped to specific reovirus gene segments, suggesting that ERK activation and JNK activation are triggered by different events during virus-host cell interaction.

* Corresponding author. Mailing address: Department of Neurology (127), Denver VA Medical Center, 1055 Clermont St., Denver, CO 80220. Phone: (303) 393-2874. Fax: (303) 393-4686. E-mail: Ken.Tyler{at}uchsc.edu.

dagger Present address: Institute de Biologie Cellulaire et de Morphologie, Lausanne, Switzerland.

Journal of Virology, December 2001, p. 11275-11283, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11275-11283.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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