Importance of Amino Acid 14 (Valine) within Capsid Protein VP2 of Theiler's Murine Encephalomyelitis Virus (TMEV) for Its Neurovirulence

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Abstract

The GDVII strain of Theiler's murine encephalomyelitis virus (TMEV) is highly neurovirulent, and induces acute fatal polioencephalomyelitis in mice. In contrast, the DA strain of TMEV is less neurovirulent, and induces non-fatal polioencephalomyelitis of weanling mice followed by chronic inflammatory demyelination with viral persistence in the spinal cords. The IB (VP2)-1D (VP1) coding region is reported to be one of the neuro virulence determinants of TMEV by Zhang et al (Zhang L, Senkowski A, Shim B et al : J Virol 1993 ; 67 : 4404-8). In order to examine whether valine at amino acid position 14 (val-14) in the IB (VP2) coding region is responsible for the neurovirulence of TMEV, we generated a mutant virus, GDVII_<Leu>, in which val-14 is mutated to leucine. GDVII_<Leu> virus was dramatically attenuated compared with the parental GDVII, and the histopathological findings induced by GDVII_<Leu> were as mild as those induced by the DA strain. The results suggest that val-14 in the IB (VP2) coding region may be responsible for the neurovirulence of TMEV.

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