Reovirus infection activates JNK and the JNK-dependent transcription factor c-Jun

Viral infection often perturbs host cell signaling pathways including those involving mitogen-activated protein kinases (MAPKs). We now show that reov irus infection results in the selective activation of c-Jun N-terminal kina se (JNK). Reovirus-induced JNK activation is associated with an increase in the phosphorylation of the JNK-dependent transcription factor c-Jun. Reovi rus serotype 3 prototype strains Abney (T3A) and Dearing (T3D) induce signi ficantly more JNK activation and c-Jun phosphorylation than does the seroty pe 1 prototypic strain Lang (TIL). T3D and T3A also induce more apoptosis i n infected cells than TIL, and there was a significant correlation between the ability of these viruses to phosphorylate c-Jun and induce apoptosis. H owever, reovirus-induced apoptosis, but not reovirus-induced c-Jun phosphor ylation, is inhibited by blocking TRAIL/receptor binding, suggesting that a poptosis and c-Jun phosphorylation involve parallel rather than identical p athways. Strain-specific differences in JNK activation are determined by th e reovirus S1 and M2 gene segments, which encode viral outer capsid protein s (sigma1 and mu 1c) involved in receptor binding and host cell membrane pe netration. These same gene segments also determine differences in the capac ity of reovirus strains to induce apoptosis, and again a significant correl ation between the capacity of T1L X T3D reassortant reoviruses to both acti vate JNK and phosphorylate c-Jun and to induce apoptosis was shown. The ext racellular signal-related kinase (ERK) is also activated in a strain-specif ic manner following reovirus infection. Unlike JNK activation, ERK activati on 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.