dc.contributor.author | Gangadharan, Babunilayam | en |
dc.date.accessioned | 2018-05-14T10:13:00Z | |
dc.date.available | 2018-05-14T10:13:00Z | |
dc.date.issued | 2006 | |
dc.identifier.uri | http://hdl.handle.net/1842/29773 | |
dc.description.abstract | | en |
dc.description.abstract | Intranasal 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.abstract | Sequential 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.abstract | The 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.abstract | Other 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.publisher | The University of Edinburgh | en |
dc.relation.ispartof | Annexe Thesis Digitisation Project 2018 Block 18 | en |
dc.relation.isreferencedby | Already catalogued | en |
dc.title | Role of gamma interferon in the pathogenesis of Murine gannaherpesvirus-68 | en |
dc.type | Thesis or Dissertation | en |
dc.type.qualificationlevel | Doctoral | en |
dc.type.qualificationname | PhD Doctor of Philosophy | en |