Low Intra-Host and Inter-Host Genetic Diversity of Carnivore Protoparvovirus 1 in Domestic Cats During A Feline Panleukopenia Outbreak

Feline panleukopenia (FPL), a highly contagious and frequently fatal disease of cats, is caused by Feline parvovirus (FPV) and Canine parvovirus (CPV). We characterized 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 X coverage per site. All samples comprised FPV alone. Compared to the reference FPV genome, isolated in 1967, 44 mutations were detected. Ten of these were non-synonymous, including 9 in non-structural genes and one in VP1/VP2 (Val232Ile), which was the only one to exhibit inter-host diversity, being present in five sequences. There were five other polymorphic nucleotide positions, all with synonymous mutations. Intra-host diversity at all polymorphic positions was low with sub-consensus variant frequencies (SVF) of >1% except for two positions (2108 and 3208) in two samples with SVF of 1.1 – 1.3%. Intra-host 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, intra-host viral genetic diversity was limited and most mutations observed were synonymous, indicative of a low background mutation rate and strong selective constraints.