Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item The Effect of acyclovir on the acute and latent murine gammaherpesvirus-68 infection of mice(Sage Publishing, 1994) Sunil-Chandra, N.P.; Efstathiou, S.; Nash, A.A.Mice inoculated intranasally with murine gammaherpesvirus-68 were used to evaluate the efficacy of acyclovir (ACV) in the treatment of acute and latent infections. Effectiveness was measured by infectious virus assay of the lung (site of active replication) and infectious centre assay of spleen cells (site of latency). Intraperitoneal administration of ACV at 6-h intervals starting soon after inoculation was more effective in reducing infectious virus in the lung than was treatment with 12-hourly injections commencing 3 days post-infection.Item Interactions of murine gammaherpesvirus 68 with B and T cell lines(Academic Press, Elsevier, 1993) Sunil-Chandra, N.P.; Efstathiou, S.; Nash, A.A.Murine gammaherpesvirus is a natural pathogen of wild rodents. We have established that in vivo the virus persists in B lymphocytes in a latent form and therefore has similar biological properties to Epstein-Barr virus and related gamma-I-herpesviruses. In this report we have established a persistent infection in mouse myeloma (B) cells (NSO cell line), but not in mouse thymoma (T) cells (BW 5147 cell line). The virus persists indefinitely in myeloma cells, without any apparent cytopathic effect, but with the production of infectious virus. We demonstrate that ACV abolishes the productive infection, but large numbers of cells harbor the virus in a latent form, as determined by an infectious center assay. Analysis of the viral DNA has shown that during a persistent infection linear virus genomes predominated, with low levels of circular DNA also present. Treatment of cells with ACV results in a significant reduction of linear genomes, but has no effect on the level of circular DNA molecules. These data provide further evidence to support our earlier observations on B cells as the site of latency and provides an in vitro model with which to study the molecular basis of MHV-68 latency/persistence.Item Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68(American Assn. of Pathologists; Elsevier, 1994) Sunil-Chandra, N.P.; Arno, J.; Fazakerley, J.; Nash, A.A.Murine gammaherpesvirus is a natural pathogen of wild rodents. In the laboratory it establishes an infection of epithelial cells and persists in B lymphocytes in a latent form. Inbred mice chronically infected with the virus develop a lymphoproliferative disease (LPD) similar to that seen in patients infected with Epstein-Barr virus. The frequency of LPD over a period of 3 years was 9% of all infected animals, with 50% of these displaying high grade lymphomas. The incidence of LPD was greatly increased when infected mice were treated with cyclosporin A. The majority of mice used in the experiments were BALB/c, although lymphomas were detected in mice on other genetic backgrounds, ie, CBA and B10Br. Lymphomas were associated with both lymphoid and nonlymphoid tissues (liver, lung, and kidney). In all cases of lymphomas studied thus far, there was a mixed B cell (B220+ve) and T cell (CD3+ve) phenotype. The B cells were light chain restricted, indicative of a clonal origin. Variable numbers of virus genome-positive cells were detected by in situ hybridization in and around the lymphomas. In contrast, no lytic antigen-positive cells were detected, indicating that genome-positive cells were either latently infected or undergoing an abortive infection. These observations suggest that murine gammaherpesvirus-infected mice may be an important model to study the pathogenesis of LPD associated with other gammaherpesviruses, such as Epstein-Barr virus.Item 2'-Deoxy-5-ethyl-beta-4'-thiouridine inhibits replication of murine gammaherpesvirus and delays the onset of virus latency(International Medical Press, 1999) Barnes, A.; Dyson, H.; Sunil-Chandra, N.P.; Collins, P.; Nash, A. A.The antiviral thionucleoside analogue 2'-deoxy-5-ethyl-beta-4'-thiouridine (4'-S-EtdU) was shown to be a more potent inhibitor of gammaherpesvirus infection than acyclovir. This compound inhibits replication of murine herpesvirus (MHV)-68 in the lungs of mice when given 3 days post-infection. However, as with other nucleoside analogues, it was unable to prevent the establishment of latency, despite delaying the onset of latent infection in the spleen. In contrast, virus persistence in the lung was inhibited following drug treatment, although persistence was re-established in mice when treatment was suspended after 12 days. These data suggest that 4'-S-EtdU is a highly effective inhibitor of murine gamma herpesvirus replication and as such provides a powerful tool to study the pathogenesis of this virus in vivo.