title: The L-coding region of the DA strain of Theiler's murine encephalomyelitis virus causes dysfunction and death of myelin-synthesizing cells.
abstract: The DA strain and other members of the TO subgroup of Theiler's murine encephalomyelitis virus (TMEV) induce an early transient subclinical neuronal disease followed by a chronic progressive inflammatory demyelination, with persistence of the virus in the central nervous system (CNS) for the life of the mouse. Although TMEV-induced demyelinating disease (TMEV-IDD) is thought to be immune mediated, there is also evidence that supports a role for the virus in directly inducing demyelination. In order to clarify the function of DA virus genes, we generated a transgenic mouse that had tamoxifen-inducible expression of the DA L-coding region in oligodendrocytes (and Schwann cells), a cell type in which the virus is known to persist. Tamoxifen-treated young transgenic mice usually developed an acute progressive fatal paralysis, with abnormalities of the oligodendrocytes and Schwann cells and demyelination, but without significant lymphocytic infiltration; later treatment led to transient weakness with demyelination and persistent expression of the recombined transgene. These findings demonstrate that a high level of expression of DA L can cause the death of myelin-synthesizing cells and death of the mouse, while a lower level of L expression (which can persist) can lead to cellular dysfunction with survival. The results suggest that expression of DA L plays an important role in the pathogenesis of TMEV-IDD. Virus-induced infection and death of oligodendrocytes may play a part in the demyelination of other diseases in which an immune-mediated mechanism has been stressed, including multiple sclerosis.
authors.affiliation: Department of Neurology, The University of Chicago Medical Center, 5841 S. Maryland Ave., MC2030, Chicago, IL 60637, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Ghadge
authors.forename: R
authors.initials: R
authors.lastname: Wollmann
authors.forename: G
authors.initials: G
authors.lastname: Baida
authors.forename: M
authors.initials: M
authors.lastname: Traka
authors.forename: R P
authors.initials: RP
authors.lastname: Roos
mesh_terms: D000818:Animals; D016923:Cell Death; D003711:Demyelinating Diseases; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D009836:Oligodendroglia / Q000473:pathology / Q000821:virology; D011051:Poliomyelitis / Q000473:pathology / Q000821:virology; D012367:RNA, Viral / Q000235:genetics*; D012376:Rodent Diseases / Q000473:pathology / Q000821:virology; D012583:Schwann Cells / Q000473:pathology / Q000821:virology; D017945:Theilovirus / Q000472:pathogenicity*; D014764:Viral Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins; D037521:Virulence Factors