Summary auto-generated
This study investigated the role of perforin, a cytotoxic protein released by immune cells, in controlling murine gammaherpesvirus 68 (MHV-68) infection. Researchers compared infection outcomes in transgenic perforin-deficient mice versus normal C57BL/6 mice following intranasal virus exposure. MHV-68 causes acute lung infection followed by latent infection in B lymphocytes, serving as a model for human gammaherpesvirus infections like Epstein-Barr virus. Although CD8+ T cells are essential for controlling this infection, the study found that perforin deficiency did not significantly affect virus clearance from lungs or the establishment and control of latent infection in the spleen. Lymphocytes from both mouse strains showed comparable cytotoxic T lymphocyte (CTL) activity and secreted similar levels of antiviral cytokines (IFN-γ, IL-10, IL-6). These findings demonstrate that perforin-mediated killing is not required for immune control of MHV-68, contrasting with lymphocytic choriomeningitis virus where perforin is essential. The results suggest CD8+ T cells may control MHV-68 through alternative mechanisms such as cytokine secretion or other non-cytolytic pathways rather than direct cell lysis.
Key findings
- Perforin-deficient mice effectively control MHV-68 acute lung infection with kinetics similar to wild-type mice
- Latent spleen infection and numbers of latently infected B cells are controlled normally without perforin
- CD8+ T cells from perforin-deficient mice maintain comparable cytotoxic activity and cytokine production to control mice
- Unlike lymphocytic choriomeningitis virus, perforin-mediated killing is dispensable for immunity to this gammaherpesvirus
- Alternative CD8+ T cell effector mechanisms, likely involving cytokine secretion, can compensate for lack of perforin in controlling MHV-68
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Abstract
Perforin-mediated cytotoxic T cell killing has been suggested to be of importance in the control of noncytopathic virus infections, based on studies with lymphocytic choriomeningitis virus (LCMV). We examined the role of perforin in a mouse model of gammaherpesvirus infection using transgenic perforin-deficient mice. Previous work from this laboratory has shown that CD8 T cells are essential for the resolution of the acute lung infection and control of latently infected B cells in murine gamma-herpesvirus 68 infection. The absence of perforin did not significantly affect the kinetics of either the lytic lung infection or the latent spleen infection. Lymphocytes from both perforin-deficient and control mice secreted comparable levels of IFN-gamma, IL-10 and IL- 6. In addition, lymphocytes from both strains had similar levels of CD3epsilon-dependent cytotoxic activity in the spleen, draining lymph nodes and bronchoalveolar lavage. These data indicate that the lack of perforin has little affect on the ability of mice to control an experimental gammaherpesvirus infection.