L-ASTERISK PROTEIN OF THE DA STRAIN OF THEILERS MURINE ENCEPHALOMYELITIS VIRUS IS IMPORTANT FOR VIRUS GROWTH IN A MURINE MACROPHAGE-LIKE CELL-LINE

Strain GDVII and other members of the GDVII subgroup of Theiler's muri ne encephalomyelitis virus (TMEV) are highly virulent and cause acute polioencephalomyelitis in mice. Neither viral persistence nor demyelin ation is demonstrated in the few surviving mice. On the other hand, st rain DA and other members of the TO subgroup of TMEV are less virulent and establish a persistent infection in the spinal cord, which result s in a demyelinating disease. We previously reported that GDVII does n ot actively replicate in a murine macrophage-like cell line, J774-1, w hereas DA strain productively infects these cells (hl. Obuchi, I: Ohar a, T, Takegami, T, Murayama, H. Takada, and H. Iizuka, J, Virol, 71:72 9-733, 1997), In the present study, we used recombinant viruses betwee n these strains of the two subgroups to demonstrate that the DA L codi ng region of DA strain is important for virus growth in J774-1 cells. Additional experiments with a mutant virus indicate that L protein, w hich is synthesized out of frame with the polyprotein from an addition al alternative initiation codon in the L coding region of TO subgroup strains, is a key determinant responsible for the cell-type-specific r estriction of virus growth, L protein may play a critical role in the DA-induced restricted demyelinating infection by allowing growth in m acrophages, a major site for virus persistence.