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Title: The role of the acquired immune response in virus clearance and neuropathology in Semliki Forest virus infection
Author: Ballany, Catherine Miriam Dixon
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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This thesis examines the role of acquired immune responses in Semliki Forest virus (SFV) encephalitis. The role of components of the acquired immune response in mediating clearance of infectious virus and virus RNA and in the pathogenesis of demyelination was examined using mice with genetic deletions affecting components of acquired immune responses. This included mice deficient in CD4+ and CD8+ T-cell responses and specific T-cell mediators IFNγ, perforin and Fas. Analysis of inflammatory infiltrates in the SFV infected CNS demonstrated a rapid influx of macrophages and NK cells and a >40-fold increase in T-lymphocytes, predominantly CD8+ cells. Mice lacking CD8+ T-cells mediated the demyelinating lesions.  Mice lacking CD4+ T-cells were unable to generate good antibody responses and were unable to clear infectious virus. Transfer of anti-SFV hyperimmune (HI) serum to SFV infected SCID mice lowered virus RNA to levels comparable to those in immunocompetent (BALB/c) mice. However, antibody alone was not sufficient to eliminate virus RNA and infectious virus reappeared once antibody levels dropped. IFNγR-/- mice were found to have slower clearance of virus RNA compared to wild-type mice but IFNγ was not necessary for the development of demyelinating lesions. A protective role for IFNγ was demonstrated in SFV infection; recombinant IFNγ transiently protected SFV infected IFNα/βR-/- mice. Neither perforin nor Fas was necessary for clearance of infectious virus or viral RNA. SFV infected Fas knock-out mice had increased CNS demyelination. In summary, this thesis demonstrates that in SFV infection, CD8+ T-cells are the main component of the CNS inflammatory response. It is likely that both antibody and CD8+ T-cells are required to eliminate SFV infection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available