In the middle of the past century, the Australian government took advantage of the species specificity of myxoma virus to control the spread of European wild rabbits, by then considered a pest. Although other poxviruses display specificity to varying degrees, it is not clear what influences host/virus compatibility.
Wang et al. observed that myxoma virus infection of primary mouse embryo fibroblasts, which are nonpermissive for replication of this virus, activated the kinase Erk1/2. In the presence of an Erk1/2 inhibitor or in cells with impaired Erk1/2 expression, viral replication increased, suggesting that this kinase normally represses this virus. Erk1/2 is linked with interferon regulatory factor 3, which in turn induces expression of type I interferons (IFNs). The possibility that these cytokines maintain the nonpermissive state induced by Erk1/2 activation is supported by the fact that cells unable to produce IFNs or the IFN-dependent transcription factor STAT-1 became susceptible to myxoma infection. Furthermore, STAT-1-deficient mice succumbed to inocula of the virus that had no effect on wild-type animals, raising the possibility that similar cellular mechanisms may govern species specificity of other poxviruses. -- SJS
Nature Immunol. 5, 1266 (2004).
