Porcine cytomegalovirus: Diagnosis, pathogenesis and control.

摘要

Porcine cytomegalovirus (PCMV) infection has been known since 1955, and although it seems to be widely distributed in the swine population, very little is known about the virus itself and the patterns of infection in pigs. Due to the increased interest in xenotransplantation, and the potential of PCMV being an important pathogen in this context, there is a need to better understand the mechanisms of PCMV pathogenesis and to study ways to control the infection in pigs. The overall goals of this thesis were to develop assays to be used to detect PCMV, to characterize the mechanisms of pathogenesis involved in PCMV infection in pigs and to determine if PCMV is susceptible to antiviral treatment. The first section describes studies performed to develop and optimize methods of PCMV detection. A PCR test to detect PCMV in infected cell culture and tissues from naturally and experimentally infected pigs was optimized, followed by the development of an in situ hybridization assay to detect PCMV within infected cells and tissues. The second section addresses the replication and localization of PCMV in porcine fetuses inoculated in utero, as well as the effect of immunosuppressive therapy on PCMV pattern of infection in nursery pigs. In both studies, PCMV could be found in different tissues in infected fetuses and in immunosuppressed pigs, showing a generalized pattern of infection. Furthermore, studies were performed in order to demonstrate that latent PCMV could be reactivated, in vitro, through allogeneic stimulation of co-cultured peripheral blood mononuclear cells (PBMCs). It was shown that the allogeneic stimulation of PBMCs was sufficient to induce reactivation of PCMV. In the third section, the in vitro and in vivo susceptibility of PCMV to the antiviral drug ganciclovir was determined in order to elucidate ways to control PCMV infection. It was shown that PCMV is susceptible to ganciclovir, both in vitro and in vivo. In summary, new information about PCMV pathogenesis and ways to detect and control it were achieved in this thesis.