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Chapter 34 : Pathogenesis of Theiler's Murine Encephalomyelitis Virus-Induced Disease

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Abstract:

Strains of Theiler’s murine encephalomyelitis virus (TMEV) were first isolated by Max Theiler at the Rockefeller Foundation during his investigations of yellow fever virus vaccine. The GDVII strain of TMEV was named because this isolate was the seventh made by George, Theiler’s technician, from an uninoculated mouse that was found to be diseased (paralyzed). The presence of polypyrimidine tract binding protein (PTB) and nPTB binding sites in GDVII affects neurovirulence. The importance of sialic acid binding to virus entry is further supported by studies that showed that a variant of DA that has enhanced binding to L929 cells and has mutations in the VP2 puff B or VP1 loop 2; this region is also one that has been found important in disease pathogenesis. It was found that demyelination can occur when one replaces any part of the DA genome with the corresponding segment from the GDVII genome. In addition, the immune system is believed to mediate the pathology in both diseases. Therefore, it is hoped that investigations of TMEV-induced demyelination may provide insights into the pathogenesis of multiple sclerosis. The identity of the TMEV receptor, or what are probably TMEV receptors, is likely to help clarify the pathogenesis of TMEV-induced central nervous system disease. In addition, the identification of cell-specific RNA-binding proteins that affect translation and regulate the synthesis of L* versus the polyprotein is also likely to help in the understanding of picornaviral gene expression and TMEV disease pathogenesis.

Citation: Roos R. 2002. Pathogenesis of Theiler's Murine Encephalomyelitis Virus-Induced Disease, p 427-435. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch34

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Central Nervous System Diseases
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Theiler's Murine Encephalomyelitis
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Figures

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FIGURE 1

The TMEV single-stranded RNA of approximately 8,100 nucleotides. The 5′ UTR precedes the polyprotein coding region, which has the leader (L) coding region as its most amino terminus; a 3′ UTR is at the 3′ end of the genome. The genomic region of P1 is divided into 1A, 1B, 1С, and 1D coding regions, which synthesize, respectively, the structural proteins VP4, VP2, VP3, and VP1. P2 (which includes 2A, 2B, 2C, and 2D) and P3 (which includes 3А, 3B, 3C, and 3D) encode various nonstructural proteins. The polyprotein's initiation codon is at nucleotide 1066, while the initiation codon for L* in the case of the DA strain of TMEV is at nucleotide 1079. There is a stop codon (UAG) for L* at nucleotide 1547. The GDVII strain of TMEV has an ACG rather than an AUG in the position corresponding to the DA L* initiation codon, so GDVII fails to synthesize L*.

Citation: Roos R. 2002. Pathogenesis of Theiler's Murine Encephalomyelitis Virus-Induced Disease, p 427-435. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch34
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Tables

Generic image for table
TABLE 1

Phenotypic differences between TMEV subgroups

Citation: Roos R. 2002. Pathogenesis of Theiler's Murine Encephalomyelitis Virus-Induced Disease, p 427-435. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch34
Generic image for table
TABLE 2

The cytolytic response, L*, and susceptibility

Citation: Roos R. 2002. Pathogenesis of Theiler's Murine Encephalomyelitis Virus-Induced Disease, p 427-435. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch34

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