Anticapsid immunity level, not viral persistence level, correlates with the progression of Theiler's virus-induced demyelinating disease in viral P1-transgenic mice.
Intracranial infection of Theiler's murine encephalomyelitis virus (TMEV) induces demyelination and a neurological disease in susceptible SJL/J (SJL) mice that resembles multiple sclerosis. While the virus is cleared from the central nervous system (CNS) of resistant C57BL/6 (B6) mice, it persists in SJL mice. To investigate the role of viral persistence and its accompanying immune responses in the development of demyelinating disease, transgenic mice expressing the P1 region of the TMEV genome (P1-Tg) were employed. Interestingly, P1-Tg mice with the B6 background showed severe reductions in both CD4(+) and CD8(+) T-cell responses to capsid epitopes, while P1-Tg mice with the SJL background displayed transient reductions following viral infection. Reduced antiviral immune responses in P1-Tg mice led to >100- to 1,000-fold increases in viral persistence at 120 days postinfection in the CNS of mice with both backgrounds. Despite the increased CNS TMEV levels in these P1-Tg mice, B6 P1-Tg mice developed neither neuropathological symptoms nor demyelinating lesions, and SJL P1-Tg mice developed significantly less severe TMEV-induced demyelinating disease. These results strongly suggest that viral persistence alone is not sufficient to induce disease and that the level of T-cell immunity to viral capsid epitopes is critical for the development of demyelinating disease in SJL mice.
Myoung
Jinjong
J
Department of Microbiology-Immunology, Northwestern University Medical School, 303 East Chicago Ave., Chicago, IL 60611, USA.
Bahk
Young Yil
YY
Kang
Hyun Seok
HS
Dal Canto
Mauro C
MC
Kim
Byung S
BS
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001921:Brain / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002213:Capsid / Q000276:immunology* / Q000378:metabolism*; D018188:Cardiovirus Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016679:Genome, Viral / Q000235:genetics; D007108:Immune Tolerance / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D017945:Theilovirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma