Cellular immunity in Pneumovirus infections

Abstract

Human Respiratory Syncytial Virus (RSV) is the leading cause of viral respiratory tract infection in infants worldwide. In the developed world viral bronchiolitis is the most common cause of hospitalization among infants, 70% of these are associated with RSV. In recent years the realization is growing that RSV also is a considerable disease burden on adults as well. At the moment there is no effective antiviral therapy or an effective vaccine available against RSV infection. The development of a safe and working vaccine would greatly benefit from a better understanding of the interactions between the virus and its host. RSV is a negative sense, single-stranded RNA virus, part of the family of Paramyxoviridae, subfamily Pneumovirinae, genus Pneumovirus. Two closely related viruses Bovine Repiratory Syncytial virus (BRSV) and Pneumonia Virus of Mice (PVM) cause in their hosts, cattle and mice respectively, clinical symptoms reminiscent of RSV disease in humans. The aim of the research described in this thesis was to gain better insight in the (cellular) immunological responses of the hosts against pneumoviruses. Three models were used to examine the cellular immunity against pneumoviral infection, RSV in mice, BRSV in cattle, and a relatively new model, PVM in mice. Since the murine RSV model relies heavily on BALB/c mice, we have investigated the cellular immunity against RSV in C57BL/6. Five RSV-specific CD8 T cell epitopes were identified. Using the BRSV cattle infection model, the antiviral CD8 T cell reponses are analyzed. In the last model, PVM in mice, the first antiviral CD8 and CD4 T cell responses are described and their role in protection against PVM infection is examined. The results obtained with PVM in mice argue that it could represent a promising small animal model to elucidate pneumovirus host interactions.