The biological and evolutionary significance of multiple cytomegalovirus infection

[Truncated abstract] Human cytomegalovirus (HCMV) is a large DNA virus that is widespread in the human population and circulates as a large number of genetically distinct strains. Since primary infection does not provide sterilising immunity, an individual may become re-infected over the course of a lifetime. Infection by multiple HCMV strains has been documented in both healthy and immunocompromised individuals and has been linked to increased disease in certain patient groups. The mechanism of this enhanced disease is unknown but may be due to complementary interactions between viral strains resulting in higher viral loads. The aim of this thesis was to test the hypothesis that multiple CMV infection leads to the enhancement of global viral fitness through functional complementation. Murine CMV (MCMV) also circulates within mice as genetically distinct strains with infection by multiple strains documented in individual free-living wild mice. A panel of low-passage, wild-derived MCMV strains was utilised to develop a mouse model of multiple-infection with the aim of defining mechanisms of enhanced disease. For these studies, four wild-derived MCMV strains, C4A, C4B, C4C, and C4D, were selected as representatives of circulating strains within the population. Whole genome sequencing confirmed that these four MCMV strains were unique and sufficient genetic variability was observed between these strains which could provide a platform for in vivo complementation and (Chapter 4). A novel, MCMV strain-specific multiplex qPCR developed for this investigation, permitted the identification and quantification of strains recovered from co-infection (Chapter 3).