Insights into Theiler's virus neurovirulence based on a genomic comparison of the neurovirulent GDVII and less virulent BeAn strains

Theiler's murine encephalomyelitis viruses (TMEV) are naturally occurring enteric pathogens of mice which can be divided into two subgroups based primarily on their neurovirulence after intracerebral inoculation: the highly virulent GDVII group and the less virulent TO strains. To begin to elucidate the molecular basis of neurovirulence of the two TMEV subgroups, we have cloned and sequenced the entire 8105 nucleotide RNA genome of the highly virulent GDVII virus and compared it to the less virulent BeAn 8386 virus ( D. C. Pevear, M. Calenoff, E. Rozhon, and H. L. Lipton (1987) J. Virol. 61, 1507–1516). The viruses are 90.4% identical at the nucleotide level. The highest level of nucleotide identity is in the 5′ and 3′ noncoding regions of the RNAs (95.5 and 99.2%, respectively): regions believed to be important for control of viral RNA synthesis, initiation of translation, encapsidation, and virion uncoating. The 2303 amino acid polyproteins of BeAn and GDVII viruses are 95.7% identical at the amino acid level (99 of 2303 residues differed). Thirty-nine of these amino acid differences occur in the three surface coat proteins, VP1 (20 differences), VP2 (10 differences), and VP3 (9 differences), while the remainder of the changes are distributed throughout the polyprotein. Although these levels of identity are too low to determine where neurovirulence maps based solely on nucleotide sequence analysis, having the complete sequence will facilitate construction of recombinant BeAn-GDVII viruses to be used for this purpose.