The infection of mouse by Theiler's virus: from genetics to immunology

Abstract

Theiler's virus is a picornavirus of mouse which causes an acute encephalomyelitis followed by a persistent infection of the white matter of the spinal cord with chronic inflammation and demyelination. This late disease is studied as a model for multiple sclerosis. Inbred strains of mice differ in their susceptibility to persistent infection and demyelination. Resistant strains clear the infection after the acute encephalomyelitis. This observation is the basis of genetic studies which we used as a thread for this review. The H-2D locus has a major effect on susceptibility. The H-2Db gene is involved in a fast and intense CTL response which confers resistance. The Tcrb locus is also implicated, although there is no proof that the susceptibility gene in this region codes for the T-cell receptor. A complete screen of the genome uncovered the role of the Ifng locus and led to the demonstration that IFN-gamma limits viral spread in the white matter. The roles of NK cells and B cells in limiting the infection are discussed. CD4+ T cells participate both in protection against the infection and in demyelination. Finally, the effect of non-immune factors in resistance is illustrated by mice with mutations in the MBP or PLP gene.

H-2Db−/−Mice Are Susceptible to Persistent Infection by Theiler's Virus

“…The generally held view is that the H-2D b gene brings about resistance by efficient viral epitope presentation resulting in viral clearance by cytotoxic T lymphocytes (CTL) and prevention of demyelination (13,19).…”

“…The DA strain of Theiler's virus, a picornavirus of mice, causes a persistent infection of the spinal cord with primary demyelination which is one of the best models of multiple sclerosis (19). The disease that follows intracranial inoculation is biphasic.…”

Non-AUG-Initiated Internal Translation of the L* Protein of Theiler's Virus and Importance of This Protein for Viral Persistence

“…Neurovirulent strains, such as GDVII, replicate permissively in the neurons of the brain and cause acute fatal encephalitis. Persistent strains, such as DA or BeAn, induce a biphasic disease (4,11,18). During the early phase, the virus replicates in the gray matter of the brain, causing subclinical encephalitis.…”

Attenuation of neurovirulence of Theiler's murine encephalomyelitis virus strain GDVII is not sufficient to establish persistence in the central nervous system.

“…Fax j1 708 570 1568. e-mail hllipton!merle.acns.nwu.edu pathological damage of myelin is mediated by major histocompatibility (MHC) class II-restricted Th1 lymphocytes directed at virus epitope(s) (Miller et al, 1990 ;Welsh et al, 1990 ;Lipton et al, 1997 ;Monteyne et al, 1997).…”