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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 A Novel murine model for studying antiviral compounds against EBV.(International Medical Press, 1994) Sunil-Chandra, N.P.; Barnes, A.G.C.; Nash, A.A.Animal models have been of great importance in for the study of herpes virus parthenogenesis by providing systems with which to investigate basic virological and immunological aspects of acute and latent infection, and also to evaluate chemotherapeutic and vaccination regimens.The best examples are those models used to study acute, latent and recurrent herpes simplex virus (HSV) 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 Pathogenesis of murine gammaherpesvirus infection in mice deficient in CD4 and CD8 T cells(American Society for Microbiology., 1993) Ehtisham, S.; Sunil-Chandra, N.P.; Nash, A.A.Murine gammaherpesvirus is a natural pathogen of wild mice. The virus infects alveolar cells and spleen cells during the primary infection and establishes a latent/persistent infection in B lymphocytes. Little is known about the immunological response to gammaherpesviruses during a primary infection. To address this issue, we investigated the pathogenesis of murine herpesvirus 68 (MHV-68) infection in mice deficient in CD4 or CD8 T-cell populations. Infection of the lung and spleen were greatly exacerbated in CD8-deficient mice, reflected by elevated virus titers in the lung and an increase in the number of infected splenocytes located around germinal centers. This finding contrasts with clearance of virus from the lung and spleen by day 12 postinfection in CD4-depleted animals. These data clearly indicate a major role for CD8 T cells in recovery from an acute MHV-68 infection. Whereas CD4 T cells fail to influence the course of infection in the lung, they do contribute to lymphoproliferation seen in the spleen (splenomegaly) during the primary infection. The significance of these results are discussed in relation to the immune response to other herpesviruses, in particular Epstein-Barr virus, with which MHV-68 shares similar molecular and biological properties.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 Isolation and subgrouping of rotaviruses from buffalo calves in Sri Lanka(British Veterinary Association, Elsevier, 1996) Sunil-Chandra, N.P.; Mahalingam, S.Twenty-eight faecal specimens from Sri Lankan buffalo calves shown to be positive for rotavirus group A antigen were subgrouped by an enzyme-linked immunosorbent assay, by using monoclonal antibodies prepared against subgroup I and II antigens. The 13 of the 28 specimens which were classified as strongly positive belonged to subgroup I. Three of five faecal specimens inoculated on to roller cultures of MA104 cells yielded group A subgroup I rotavirus. As with other group A rotaviruses isolated from human beings and young animals, the buffalo isolates required pre-treatment with trypsin and to have trypsin incorporated in the maintenance medium, and the inoculated cell cultures had to be rolled; at least six serial passages were required before distinct rotavirus cytopathic effects were produced in the MA104 cells.Item Rotavirus-associated diarrhoea in buffalo calves in Sri Lanka(British Veterinary Association, Elseveir, 1994) Sunil-Chandra, N.P.; Mahalingam, S.Faecal samples from 150 buffalo calves, one to 150 days old, located in various districts of Sri Lanka, were examined for group A rotavirus antigen by a screening enzyme linked immunosorbent assay (ELISA). Positive samples were confirmed by the blocking ELISA. In the calves studied 27.3 per cent were diarrhoeic, and the rest were non-diarrhoeic but were in contact with the animals showing diarrhoea. Antigen was detected in 36.6 per cent of the diarrhoeic animals and in 11.9 per cent of the non-diarrhoeic animals. There was a strong association between the presence of antigen in faeces and diarrhoea in these animals (chi 2 = 46.98; P < 0.001). Of the 146 serum samples examined for antirotaviral antibodies, by the blocking ELISA at a single serum dilution (1:20) against a constant dose of antigen (8 units), 68.5 per cent were positive indicating a widespread infection with the virus in the population studied. This is the first record of the detection of rotavirus and its association with diarrhoea in buffalo calves in Sri Lanka.