Genetics of susceptibility to Theiler's virus infection

Theiler's virus is a picornavirus of mouse which causes an acute encephalomyelitis followed by a persistent infection of the white matter resulting in chronic inflammation and demyelination. This disease has been studied as a model for multiple sclerosis. Inbred strains of mice are either resistant--they clear the infection after the acute encephalomyelitis--or susceptible to persistent infection and demyelination. Susceptibility is a polygenic trait which has been analyzed using methods of association with “candidate” genes, and linkage analysis after a complete genome scan. The H-2D^b gene is responsible for an efficient CTL response which makes some strains resistant. Non H-2 genes responsible for the susceptibility of other strains have been mapped by linkage analysis to the Ifng and, possibly, the Mbp loci. The analysis of a set of congenic mice ruled out the possiblity that the relevant gene codes for interferon gamma, and showed that the region around Ifngprobably contains two susceptibility genes. The analysis of mutant mice showed further that the Mbp gene, which codes for the myelin basic protein, has a major effect on viral persistence. BioEssays 20 :627–633, 1998. © 1998 John Wiley & Sons Inc.