A nonstructural viral protein, L*, influences viral persistence and demyelination induced by Theiler's murine encephalomyelitis virus (TMEV)

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Theiler's murine encephalomyelitis virus (TMEV) is divided into two subgroups on the basis of their different biological activities. The strains belonging to GDVII subgroup produce acute and fatal poliomyelitis in mice without virus persistence or demyelination. In contrast, the strains belonging to DA or TO subgroup induce an nonfatal polioencephalomyelitis of weanling mice in the acute stage of infection followed by chronic demyelination with virus persistence in the spinal cord. A unique feature of DA (or TO) subgroup is that a 17 kDa protein, designated L*, is synthesized out-of-frame with the polyprotein. Since GDVII subgroup has an ACG rather than AUG at the initiation site and therefore does not synthesize L*, L* is thought to be a key protein for the subgroup-specific biological activities of TMEV. Studies using anti-L* protein antibody showed that L* remains stable in the cytoplasm of infected cells without being incorporated into virions, indicating that it is a nonstructural protein. A 'loss of function' experiment using DAL*-1 virus, which does not synthesize L* since the AUG at nucleotide 1079 of DA strain is mutated to ACG, demonstrated that L* protein is important for virus growth in macrophages, virus persistence and demyelination. Therefore, L* protein is multi-functional and further analysis of L* protein may help elucidate the pathomechanism(s) of TMEV-induced demyelinating disease.
金沢医科大学の論文