Low Intrahost and Interhost Genetic Diversity of

Feline panleukopenia (FPL), a highly contagious and frequently fatal disease of cats, is caused by Feline parvovirus (FPV) and Canine parvovirus (CPV). We characterised the diversity of these Carnivore protoparvovirus 1 variants in 18 faecal samples collected from domestic cats with FPL during an outbreak, using targeted parvoviral DNA metagenomics to a mean depth of >10,000 × coverage per site. All samples comprised FPV alone. Compared with the reference FPV genome, isolated in 1967, 44 mutations were detected. Ten of these were nonsynonymous, including 9 in nonstructural genes and one in VP1/VP2 (Val232Ile), which was the only one to exhibit interhost diversity, being present in five sequences. There were five other polymorphic nucleotide positions, all with synonymous mutations. Intrahost diversity at all polymorphic positions was low, with subconsensus variant frequencies (SVF) of <1% except for two positions (2108 and 3208) in two samples with SVF of 1.1−1.3%. Intrahost nucleotide diversity was measured across the whole genome (0.7−1.5%) and for each gene and was highest in the NS2 gene of four samples (1.2−1.9%). Overall, intrahost viral genetic diversity was limited and most mutations observed were synonymous, indicative of a low background mutation rate and strong selective constraints.