Alteration of amino acid 101 within capsid protein VP-1 changes the pathogenicity of Theiler's murine encephalomyelitis virus.

Theiler's murine encephalomyelitis virus (TMEV)' is a member of the picornavirus family. The icosahedral capsid consists of 60 capsomers, each containing asingle copy ofthefour capsid proteins : VP-1, VP-2, VP-3, andVP-4. Thegenome, "8,100 nucleotides long, is a single-stranded RNA of positive polarity with more thana 1,000-base-long 5' noncoding region and a poly(A) tail at theTend (1). Nucleotide sequence analysis has revealed thatTMEV is closely related to the cardioviruses, i.e ., encephalomyocarditis (EMC) and Mengo viruses (2-4) . TMEV is a naturally occurring murine virus that leads to an asymptomatic enteric infection in most young adult mice . In rare instances, a spontaneous central nervous system (CNS) disease has been observed (5) . Since its original description a number of different viral strains have been isolated . The strains can be divided into two subgroups based on their pathologic and biologic characteristics . TheGD VII/FA subgroup is highly virulent and produces an acute polio encephalitis that kills the host . In contrast, members of the TO (Theiler's original) subgroup, which include the DA strain (6), produce a biphasic disease in susceptible mice (7) . The acutedisease is similar tohuman poliomyelitis and is characterized by virus replication, inflammation, necrosis of neurons, and glial cell proliferation (8) . Survivors of the acute phase go on to develop the secondary chronic disease that is marked by spasticity of limbs (7) . The relative severity of the acute versus chronic disease is dependent on the genetic background ofthe mice (9) . In SJL/J mice, most of the infected animals survive the acute disease without exhibiting severe clinical symp