Different Strains of Theiler's Murine Encephalomyelitis Virus Antagonize Different Sites in the Type I Interferon Pathway

Author:

Stavrou Spyridon1,Feng Zongdi2,Lemon Stanley M.2,Roos Raymond P.1

Affiliation:

1. Committee of Microbiology, the University of Chicago Medical Center, 5841 S. Maryland Ave., Chicago, Illinois 60637

2. Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas

Abstract

ABSTRACT The DA strain of Theiler's murine encephalomyelitis virus (TMEV), a member of the Cardiovirus genus of the family Picornaviridae , causes persistent infection in susceptible mice, associated with restricted expression of viral proteins, and induces a demyelinating disease of the central nervous system. DA-induced demyelinating disease serves as a model of human multiple sclerosis because of similarities in pathology and because host immune responses contribute to pathogenesis in both disorders. In contrast, the GDVII strain of TMEV causes acute lethal encephalitis with no virus persistence. Cardiovirus L is a multifunctional protein that blocks beta interferon (IFN-β) gene transcription. We show that both DA L and GDVII L disrupt IFN-β gene transcription induction by IFN regulatory factor 3 (IRF-3) but do so at different points in the signaling pathway. DA L blocks IFN-β gene transcription downstream of mitochondrial antiviral signaling protein (MAVS) but upstream of IRF-3 activation, while GDVII L acts downstream of IRF-3 activation. Both DA L and GDVII L block IFN-β gene transcription in infected mice; however, IFN-β mRNA is expressed at low levels in the central nervous systems of mice persistently infected with DA. The particular level of IFN-β mRNA expression set by DA L as well as other factors in the IRF-3 pathway may play a role in virus persistence, inflammation, and the restricted expression of viral proteins during the late stage of demyelinating disease.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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