Virus Evolution In A Novel Host: Studies Of Host Adaptation By Canine Parvovirus
Virus emergence continues to pose a threat to the health of humans, companion animals, domestic agriculture and wildlife species. The processes of emergence by host switching and the subsequent adaptation of viruses to their new hosts remain poorly understood. Canine parvovirus (CPV) represents an excellent model for studying these processes. CPV emerged in the late 1970s as a host range variant of feline panleukopenia virus (FPV). The original variant, CPV-2, was rapidly replaced by a newer, presumably better-adapted variant, CPV-2a, that differs from CPV-2 in several genomic mutations, including four that alter capsid residue sequences. These studies examine the evolution and adaptation of CPV in dogs by studying the differences among CPV variants. Viruses containing intermediate capsid sequences between the original and newer CPV variants were constructed and their relative fitness was assessed by various in vitro measures. These studies suggest that CPV adaptation in dogs required intermediate viruses that had lower fitness than either wildtype virus. CPV capsid sequences have continued to mutate and multiple strains are in circulation today, including an antigenic variant, CPV-2c. These studies also examine this more recent CPV capsid variation and show that, although newer CPV variants are being selected in nature, there are currently no significant differences in disease severity or clinical outcomes among these variants. While surveillance for novel CPV variants remains important, prevention, diagnosis and treatment of parvoviral enteritis has not changed. Finally, a preliminary characterization of an in vitro model for CPV infection is presented and shows promise for use in defining additional cellular requirements for infection, in addition to the previously identified canine transferrin receptor. The model may be useful for identifying how the original CPV-2 and newer CPV variants differ in their requirements for productive infection, and may one day help us better understand the molecular mechanisms involved in host adaptation by viruses.
dissertation or thesis