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Current Topics in Virology   Volumes    Volume 4 
A small out-of-frame protein regulating the biological activities in a mouse model for human demyelinating disease
Yoshiro Ohara, Toshiki Himeda, Kunihiko Asakura
Pages: 123 - 132
Number of pages: 10
Current Topics in Virology
Volume 4 

Copyright © 2004 Research Trends. All rights reserved


Strains of Theiler’s murine encephalomyelitis virus (TMEV) are divided into two subgroups on the basis of their different biological acivities. GDVII subgroup strains produce acute and fatal poliomyelitis in mice without virus persistence or demyelination. On the other hand, DA or TO subgroup strains induce an early nonfatal polioencephalomyelitis of weanling mice followed by chronic demyelination with virus persistence in the spinal cord. One unique feature of DA (or TO) subgroup strains is that a 17 kDa protein, called L*, is synthesized out–of–frame with the polyprotein. Since GDVII subgroup strains have an ACG rather than AUG at the initiation site and therefore do not synthesize L*, L* is thought to be a key protein influencing DA biological activities. Studies using anti–L* protein antibody showed that L* remains stable in the cytoplasm of infected cells without being incorporated into virions. A ‘loss of function’ experiment using DAL*–1 virus, in which the AUG at nucleotide 1079 of DA strain is mutated to AGG, demonstrated that L* protein is important for virus growth in macrophages, virus persistence and demyelination. Therefore, L* is a multi–functional protein that is the key mediating DA biological activities. Further analysis of L* protein may help elucidate the pathomechanism(s) of TMEV–induced demyelinating disease.


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