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dc.contributor.authorGangadharan, Babunilayamen
dc.date.accessioned2018-05-14T10:13:00Z
dc.date.available2018-05-14T10:13:00Z
dc.date.issued2006
dc.identifier.urihttp://hdl.handle.net/1842/29773
dc.description.abstracten
dc.description.abstractIntranasal infection of gamma interferon receptor knockout (IFNγR⁻/⁻) mice with murine gammaherpesvirus - 68 (MHV-68) causes unique pathological changes in the spleen characterised by development and resolution of fibrosis. Delineation of virological, cellular and molecular events taking place in the spleen during these pathological changes was the main objective of this study.en
dc.description.abstractSequential histopathological and cellular characterisation studies showed early invasion of lymphoid follicles (harbouring latently infected B-lymphocytes) with CD4+ and CD8+ T lymphocytes. Concomitantly, invasion of alternatively activated macrophages characterised by arginase -1 expression was observed. These events were followed by a reduction in the number of B-lymphocytes and development of a 'fibrotic cage' around the shrinking lymphoid follicles. In spite of the decrease in the number of B-lymphocytes, the number of latently infected cells showed a progressive increase until the development of fibrosis. During fibrosis, a dramatic reduction in the number of latently infected cells was observed followed by repopulation of lymphoid follicles with B-lymphocytes indicating a recovery phase of the fibrotic response. These observations suggest that: 1) the progressive reduction and repopulation of B-lymphocytes in the lymphoid follicles of the spleen constituted the primary events during the development and resolution of fibrosis respectively. 2) Fibrosis as a host response mechanism is able to contain the expansion of latently infected cells in the spleen. 3) Presence of latently infected cells might be the trigger for fibrosis development by preventing the repopulation of lymphoid follicles.en
dc.description.abstractThe role of IFNγ responsiveness of bone marrow derived cells in the pathogenesis of splenic fibrosis was investigated by generating radiation bone marrow chimera mice and subsequent infection with MHV-68. The study showed that, replacing the bone marrow derived cells in IFNγR⁻/⁻ mice with bone marrow derived cells from wild type mice prevented the development of splenic fibrosis following MHV-68 infection.en
dc.description.abstractOther pathological changes occurred in the lung, liver, aorta and spleen of IFNγR⁻/⁻ mice infected with MHV-68. 1) Focal areas of interstitial fibrosis were observed in the lung during day 12-16 post infection. At the same time, cuffing of pulmonary vessels with primarily mononuclear cells was observed. A few of the infiltrating cells were productively infected with MHV-68 which coincided with clearing of productive infection from alveolar epithelial cells. The change in the tropism of viral infection may be related to the development of fibrosis. 2) The pathological changes observed in the liver was characterised by proliferation of intrahepatic bile ducts and infiltration of mononuclear cells around them. Productively and latently infected mononuclear cells were present among the infiltrating cells. At later stages, some of the lesions progressed to degeneration and necrosis of intrahepatic bile ducts and encircling 'onion skin' type fibrosis. The pathological changes observed in the liver mimic the changes observed in primary sclerosing cholangitis. 3) The incidence of bony metaplasia in the spleen of IFNγR⁻/⁻ mice infected with MHV-68 was higher in comparison to mock infected IFNγR⁻/⁻ mice and MHV-68 infected wild type mice. Bony metaplasia was observed in the spleen of IFNγR⁻/⁻ mice before the development of fibrosis. These observations suggest that development of bony metaplasia is independent of fibrosis. There was no direct correlation between the expression of bone morphogenic protein-4 and development of bony metaplasia in the spleen. 4) The incidence of chronic arteritis at the base of aorta was in the range of 6-11% and viral antigen was demonstrated in the tunica media of blood vessels.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2018 Block 18en
dc.relation.isreferencedbyAlready catalogueden
dc.titleRole of gamma interferon in the pathogenesis of Murine gannaherpesvirus-68en
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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