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J Virol, June 1998, p. 4950-4955, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

L* Protein of the DA Strain of Theiler's Murine Encephalomyelitis Virus Is Important for Virus Growth in a Murine Macrophage-Like Cell Line

Hisashi Takata,1 Masatsugu Obuchi,2 Jiro Yamamoto,1 Takato Odagiri,2 Raymond P. Roos,3 Hideaki Iizuka,1 and Yoshiro Ohara2,*

Departments of Neurosurgery1 and Microbiology,2 Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan, and Department of Neurology, University of Chicago, Chicago, Illinois 606373

Received 23 October 1997/Accepted 22 February 1998

Strain GDVII and other members of the GDVII subgroup of Theiler's murine encephalomyelitis virus (TMEV) are highly virulent and cause acute polioencephalomyelitis in mice. Neither viral persistence nor demyelination is demonstrated in the few surviving mice. On the other hand, strain DA and other members of the TO subgroup of TMEV are less virulent and establish a persistent infection in the spinal cord, which results in a demyelinating disease. We previously reported that GDVII does not actively replicate in a murine macrophage-like cell line, J774-1, whereas DA strain productively infects these cells (M. Obuchi, Y. Ohara, T. Takegami, T. Murayama, H. Takada, and H. Iizuka, J. Virol. 71:729-733, 1997). In the present study, we used recombinant viruses between these strains of the two subgroups to demonstrate that the DA L coding region of DA strain is important for virus growth in J774-1 cells. Additional experiments with a mutant virus indicate that L* protein, which is synthesized out of frame with the polyprotein from an additional alternative initiation codon in the L coding region of TO subgroup strains, is a key determinant responsible for the cell-type-specific restriction of virus growth. L* protein may play a critical role in the DA-induced restricted demyelinating infection by allowing growth in macrophages, a major site for virus persistence.

* Corresponding author. Mailing address: Department of Microbiology, Kanazawa Medical University, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan. Phone: 81-76-286-2211. Fax: 81-76-286-3961. E-mail: ohara{at}kanazawa-med.ac.jp.

J Virol, June 1998, p. 4950-4955, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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