ATTENUATION OF NEUROVIRULENCE OF THEILERS MURINE ENCEPHALOMYELITIS VIRUS-STRAIN GDVII IS NOT SUFFICIENT TO ESTABLISH PERSISTENCE IN THE CENTRAL-NERVOUS-SYSTEM

Virus recombinants constructed from Theiler's murine encephalomyelitis virus (TMEV) strain GDVII, which causes a rapidly fatal encephalitis in mice, and the less virulent BeAn, which persists in the murine cent ral nervous system (CNS) and causes inflammatory demyelination, and a GDVII mutant deleted of 46 of 76 leader protein amino acids were analy sed for virus persistence in the CNS. The two recombinant and mutant v iruses principally contain GDVII sequences including the nucleotides e ncoding the polyprotein and 3' untranslated region. These viruses were found to replicate in the CNS of mice but they did not produce acute encephalitis or paralysis, i.e. they were attenuated in neurovirulence compared to the GDVII parent. More important, none of the viruses per sisted in the mouse CNS nor caused chronic demyelination, Thus, attenu ation of GDVII neurovirulence alone is not sufficient to establish TME V persistence. This result is discussed in the context of a genomic de terminant for persistence.