The genetics of the persistent infection and demyelinating disease caused by Theiler's virus.
Theiler's virus causes a persistent and demyelinating infection of the central nervous system of the mouse, which is one of the best animal models to study multiple sclerosis. This review focuses on the mechanism of persistence. The virus infects neurons for a few weeks and then shifts to white matter, where it persists in glial cells and macrophages. Oligodendrocytes are crucial host cells, as shown by the resistance to persistent infection of mice bearing myelin mutations. Two viral proteins, L and L*, contribute to persistence by interfering with host defenses. L, a small zinc-finger protein, restricts the production of interferon. L*, a unique example of a picornaviral protein translated from an overlapping open reading frame, facilitates the infection of macrophages. Susceptibility to persistent infection, which varies among inbred mouse strains, is multigenic. H2 class I genes have a major effect on susceptibility. Among several non-H2 susceptibility loci, Tmevp3 appears to regulate the expression of important cytokines.
Brahic
Michel
M
Unité des Virus Lents, URA CNRS 1930, Institut Pasteur, 75724 Paris Cedex 15, France. mbrahic@pasteur.fr
Bureau
Jean-François
JF
Michiels
Thomas
T
D000595:Amino Acid Sequence; D000818:Animals; D018188:Cardiovirus Infections / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000821:virology; D002493:Central Nervous System Diseases / Q000209:etiology / Q000235:genetics* / Q000821:virology; D003711:Demyelinating Diseases / Q000209:etiology / Q000235:genetics* / Q000821:virology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D040641:Quantitative Trait Loci; D017945:Theilovirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics
C096897:L(asterisk) protein, Theiler's encephalomyelitis virus; D008565:Membrane Proteins; D014764:Viral Proteins