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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 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 Virological and pathological features of mice infected with murine gamma-herpesvirus 68(Society for General Microbiology; Microbiology Society, 1992) Sunil-Chandra, N.P.; Efstathiou, S.; Arno, J.; Nash, A.A.The primary infection of BALB/c mice with murine herpesvirus 68 (MHV-68) was investigated. When the virus was introduced intranasally, the lung was the main tissue infected, the virus being associated with alveolar epithelium and mononuclear cells. A productive infection lasted for 10 days, after which viral DNA could be detected by in situ hybridization up to 30 days after infection. At that time lymphoproliferative accumulations were also observed in the lung, with formation of germinal centres. Virus could also be recovered from the heart, kidney, adrenal gland and spleen during the primary infection. In addition, the spleen appeared to be the major site of virus persistence, with latently infected cells detected up to 90 days post-infection. During the primary infection, there was atrophy of the thymus and spleen of clinically sick animals. In contrast, lymphoproliferative responses, typified by splenomegaly, were frequently seen in asymptomatic animals. The pattern of infection observed in MHV-68-infected mice is similar to that seen in infectious mononucleosis of man following Epstein-Barr virus infection. The model described in this paper may prove to be useful in studying natural gamma-herpesvirus infections of man and domestic animals.Item Characterization of murine gammaherpesvirus 68 glycoprotein B (gB) homolog: similarity to Epstein-Barr virus gB (gp110)(American Society for Microbiology, 1994) Stewart, J.P.; Janjua, N.J.; Sunil-Chandra, N.P.; Nash, A.A.; Arrand, J.R.Murine gammaherpesvirus 68 (MHV-68) is a natural pathogen of murid rodents and displays similar pathobiological characteristics to those of the human gammaherpesvirus Epstein-Barr virus (EBV). However, in contrast to EBV, MHV-68 will replicate in epithelial cells in vitro. It has therefore been proposed that MHV-68 may be of use as a model for the study of gammaherpesviruses, EBV in particular, both in vitro and in vivo. The EBV homolog of herpes simplex virus glycoprotein B (gB), termed gp110, is somewhat unusual compared with those of many other herpesviruses. We therefore decided to characterize the homolog of gB encoded by MHV-68 (termed MHV gB) to observe the properties of a gammaherpesvirus gB produced in epithelial cells and also to test the relatedness of MHV-68 and EBV. The MHV gB-coding sequence was determined from cloned DNA. The predicted amino acid sequence shared closest homology with gammaherpesvirus gB homologs. Biochemical analysis showed that MHV gB was a glycoprotein with a molecular weight of 105,000. However, the glycans were of the N-linked, high-mannose type, indicating retention in the endoplasmic reticulum. In line with this, MHV gB was localized to the cytoplasm and nuclear margins of infected cells but was not detected on the cell surface or in virions. Additionally, anti-MHV gB antisera were nonneutralizing. Thus, the MHV gB was unlike many other herpesvirus gBs but was extremely similar to the EBV gB. This highlights the close relationship between MHV-68 and EBV and underlines the potential of MHV-68 as a model for EBV in epithelial cells both in vitro and in vivo.Item Interactions of the murine gammaherpesvirus with the immune system(Current Science; Elsevier, 1994) Nash, A.A.; Sunil-Chandra, N.P.Our understanding of the host response to gammaherpesviruses comes largely from studies on Epstein-Barr virus. A recent addition to this family is murine herpesvirus-68 which, like Epstein-Barr virus, establishes a latent infection in B lymphocytes and is associated with lymphoproliferative disease. This virus provides a unique opportunity to explore the relationship between gammaherpesviruses and the immune system.