Not Asian Anymore: Reconstruction of the History, Evolution, and Dispersal of the "Asian" Lineage of CPV-2c

Abstract

Variability has been one of the hallmarks of canine parvovirus type 2 (CPV-2) since its discovery, and several lineages and antigenic variants have emerged. Among these, a group of viruses commonly called Asian CPV-2c has recently been reported with increasing frequency in different regions. Currently, its global epidemiology and evolution are essentially unknown. The present work deals with this information gap by evaluating, via sequence, phylodynamic, and phylogeographic analyses, all the complete coding sequences of strains classified as Asian CPV-2c based on a combination of amino acid markers and phylogenetic analysis. After its estimated origin around 2008, this lineage circulated undetected in Asia until approximately 2012, when an expansion in viral population size and geographical distribution occurred, involving Africa, Europe, and North America. Asia was predicted to be the main nucleus of viral dispersal, leading to multiple introduction events in other continents/countries, where infection establishment, persistence, and rapid evolution occurred. Although the dog is the main host, other non-canine species were also involved, demonstrating the host plasticity of this lineage. Finally, although most of the strains showed an amino acid motif considered characteristic of this lineage, several exceptions were observed, potentially due to convergent evolution or reversion phenomena.

Keywords: CPV-2; Protoparvovirus carnivoran1; canine parvovirus type 2; molecular epidemiology; parvovirus; virus evolution.

Figure 1

Temporal, host, and country distribution of sequences belonging to the Asian CPV-2c lineage annotated in GenBank. In the map at the top, the countries where the earliest sequences (2013–2016) were identified are indicated in green, while those where the viruses were found later (2017–2021) are in purple. The gray on the map indicates no sequences reported as of yet. In the lower part, countries (top) and hosts (bottom: in black, domestic animals, and in gray, other animals) are indicated in correspondence to the years when they were detected for the first time. The map was created with Mapchart.net ^©. * Classified based on NS1.

Figure 2

Key amino acids at specific residues in VP2 (left) and NS1 (right), defining Asian CPV-2c strains. In each panel, the amino acid position is indicated at the top, while the number (N) of times and percentages (%) that these sequences were found in the CPV-2c Asian (Asian) clade and in all other CPV-2 strains (non-Asian) are indicated on the right.

Figure 3

Relative genetic diversity (Ne x t) of the Asian CPV-2c lineage over the years. The results of the six independent runs have been color-coded. Mean, median, and upper and lower 95HPD values are reported for each run on the right and superimposed on the left.

Figure 4

Well-supported migration paths (i.e., BF > 10) of strains belonging to the Asian CPV-2c lineage among countries are depicted as edges whose colors are proportional to the base-10 logarithm of the migration rate. The location of each country is matched with its centroid. The results of the 6 independent analyses are reported in different panels.

Figure 5

Maximum clade credibility trees based on the Asian CPV-2c lineage VP2 dataset. The results of the phylogeographic analyses are reported with different colors. Tips and branches are color-coded according to the collection country or the one estimated with the higher posterior probability, respectively. Countries are reported in different shades of color featuring the same continent. Node size is proportional to the posterior probability of the inferred locations. The results of different datasets are reported in different panels. A comparable figure with reported tip names is provided in Supplementary Figure S4.

Figure 6

Maximum clade credibility trees based on the Asian CPV-2c lineage VP2 dataset. The results of the DTA analysis—reconstructing the evolution, over time, of the amino acids traditionally used as markers to define Asian CPV-2c strains—are reported in different panels. Tips and branches are color-coded according to the detected amino acid or the one estimated with the higher posterior probability, respectively.