How to Be a Good Host

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Science  10 Dec 2004:
Vol. 306, Issue 5703, pp. 1862
DOI: 10.1126/science.306.5703.1862c

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).

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