Semliki Forest virus-induced demyelination and remyelination--involvement of B cells and anti-myelin antibodies.
Semliki Forest virus (SFV) infection induces a demyelinating encephalomyelitis in the central nervous system (CNS) of mice and serves as a model for multiple sclerosis (MS). This study investigated CNS immune responses at different stages of infection and during SFV-induced demyelination and remyelination. Following the initial CNS inflammation, pathology and viral clearance on days 6-10 post-infection (pi), primary demyelination was observed in cerebellar, brainstem and corpus collosal white matter by days 15-21 pi, with plasma cells and microglia as main participants, and this was followed by remyelination. By day 35 pi, the tissue appeared almost normal. Fluorescent antibody cell sorter (FACS) analysis showed that brain CD8(+) T cells increased during the initial inflammatory response and gradually decreased thereafter. Brain B cell (B220(+)CD19(+)) numbers did not change significantly during the course of infection; however, from days 14 to 35 pi, they matured and produced antibodies to viral and myelin proteins (and peptides) during the period of demyelination and remyelination. The proportion of CD3(-)B220(-)CD11b(+) cells also progressively increased throughout the periods of de- and remyelination. Our results suggest that CD8(+) T cells are involved in the initial destruction of CNS tissue during the first weeks of SFV infection, while B cells, antibodies and microglia may contribute to the myelin pathology seen after recovery.
Mokhtarian
Foroozan
F
Division of Immunology, Department of Medicine, Maimonides Medical Center, Brooklyn, NY 11219, USA. fmokhtarianSUNY@aol.com
Huan
Chong-min
CM
Roman
Christopher
C
Raine
Cedric S
CS
D018354:Alphavirus Infections / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001323:Autoantibodies / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003711:Demyelinating Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D051379:Mice; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009413:Nerve Fibers, Myelinated / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012672:Semliki forest virus / Q000276:immunology*
D001323:Autoantibodies; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein