Browsing by Author "Efstathiou, S."

Now showing 1 - 5 of 5

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.
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.
Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo
(Microbiology Society, 1992) Sunil-Chandra, N.P.; Efstathiou, S.; Nash, A.A.
Murine gammaherpesvirus 68 (MHV-68) is able to persist in spleen cells of infected mice. To determine the cell type harbouring persistent virus, spleen cells from infected animals were separated into immunoglobulin (Ig)-positive (B cell-enriched), Ig-negative (T cellenriched) and plastic-adherent (macrophage-enriched) fractions. These cells were co-cultivated with permissive BHK-21 cells in an infectious centre assay. The consistent recovery and enrichment of infectious centres in the Ig-positive fraction clearly demonstrates that B cells are a major site of virus persistence/latency. This observation indicates that MHV-68 is biologically similar to Epstein-Barr virus and other members of the B cell lymphotropic gammaherpesvirus 1 subgroup.
MURINE GAMMAHERPESVIRUS 68: A MODEL TO STUDY DISEASES OF MAN AND DOMESTIC ANIMALS
(Immunobiology of viral infections, 1995) Sunil-Chandra, N.P.; J.P. Simas.; J.K, Fazakerley.; Efstathiou, S.; Nash, A.A.
The gamma herpesviruses are widely disseminated in nature causing infection and disease in man. Domestic animals including cattle, deer, sheep, horses and rodents. Murine gammaherpesvirus-68 is a natural pathogen of wild rodents. In Balb/c mice, it establishes a productive infection of epithelial cells of the lung alveoli, and a latent infection of B-Iymphocytes. As with other gammaherpesviruses, chronic infection of mice is associated with Iymphoproliferative disease (LPD) which ranges from mild to high grade lymphomas. In vitro. virus establishes persistent infection in murine myeloma B-cells in which viral DNA exists both in circular form, indicative of a latent infection and linear form, indicative of productive infection. Acyclovir can inhibit virus replication in vivo and in vitro but does not prevent latent infection in mice or reduce circular forms of viral DNA in persistently infected murine myeloma cells. CD8+ T cells are the major effector cells during acute infection. In contrast to the T-cell response which arises promptly to counter infection in the lung and spleen, antibody production (IgM) is first detectable only at 15 to 20 days. MHV-68 infection of mice provides a powerful model to study pathogenesis of gammaherpesviruses, in particular establishment and maintenance of latent infection and virus interaction with the immune system.
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.