Limited Intrahost Diversity and Background Evolution Accompany 40 Years of Canine Parvovirus Host Adaptation and Spread

Abstract

Canine parvovirus (CPV) is a highly successful pathogen that has sustained pandemic circulation in dogs for more than 40 years. Here, integrating full-genome and deep-sequencing analyses, structural information, and in vitro experimentation, we describe the macro- and microscale features that accompany CPV’s evolutionary success. Despite 40 years of viral evolution, all CPV variants are more than ∼99% identical in nucleotide sequence, with only a limited number (<40) of substitutions becoming fixed or widespread during this time. Notably, most substitutions in the major capsid protein (VP2) gene are nonsynonymous, altering amino acid residues that fall within, or adjacent to, the overlapping receptor footprint or antigenic regions, suggesting that natural selection has channeled much of CPV evolution. Among the limited number of variable sites, CPV genomes exhibit complex patterns of variation that include parallel evolution, reversion, and recombination, compromising phylogenetic inference. At the intrahost level, deep sequencing of viral DNA in original clinical samples from dogs and other host species sampled between 1978 and 2018 revealed few subconsensus single nucleotide variants (SNVs) above ∼0.5%, and experimental passages demonstrate that substantial preexisting genetic variation is not necessarily required for rapid host receptor-driven adaptation. Together, these findings suggest that although CPV is capable of rapid host adaptation, a relatively low mutation rate, pleiotropy, and/or a lack of selective challenges since its initial emergence have inhibited the long-term accumulation of genetic diversity. Hence, continuously high levels of inter- and intrahost diversity are not necessarily required for virus host adaptation. IMPORTANCE Rapid mutation rates and correspondingly high levels of intra- and interhost diversity are often cited as key features of viruses with the capacity for emergence and sustained transmission in a new host species. However, most of this information comes from studies of RNA viruses, with relatively little known about evolutionary processes in viruses with single-stranded DNA (ssDNA) genomes. Here, we provide a unique model of virus evolution, integrating both long-term global-scale and short-term intrahost evolutionary processes of an ssDNA virus that emerged to cause a pandemic in a new host animal. Our analysis reveals that successful host jumping and sustained transmission does not necessarily depend on a high level of intrahost diversity nor result in the continued accumulation of high levels of long-term evolution change. These findings indicate that all aspects of the biology and ecology of a virus are relevant when considering their adaptability.

The detection of canine parvovirus type 2c of Asian origin in dogs in Romania evidenced its progressive worldwide diffusion

“…The “Asian CPV-2c” has progressively become the dominant strain in several areas of Asia within a few years from its first identification [ 18 ], and at the same time it has also reached Europe and Africa [ 19 , 20 , 22 ]. Many of the mutations observed in CPV are short-lived and both parallel evolution and reversion are commonplace for this virus [ 10 ]. However, as CPV-2c with VP2 amino acid residues 5Gly, 267Tyr, 324Ile and 370Arg was never reported before 2013 and it has been frequently detected since then, it can be assumed that a virus with this distinctive amino acid profile is progressively expanding its spread in the world dog population, continuing to acquire mutations such as the amino acid change Ala→Gly in residue 5 [ 20 , 22 ].…”

“…The CPV antigenic variants replicate and spread more effectively in susceptible hosts, gaining the ability to infect cats [ 8 , 9 ]. The detection of other amino acid changes in the VP2 protein and the poor phylogenetic resolution supporting the three variants are leading to a progressive move away from the use of the CPV-2a, CPV-2b and CPV-2c terminology towards the use of the defining amino acid substitutions for each of these antigenic variants [ 10 ]. Nevertheless, references to the traditional nomenclature are prevalent in the literature and adopted herein.…”

Molecular Epidemiological Survey of Canine Parvovirus Circulating in China from 2014 to 2019

“…Thus, mutations in this site may have antigenic significance and affect the host immune response. This mutation was estimated to have multiple evolutionary origins [ 51 , 52 ].…”

Molecular and phylogenetic analysis of Vietnamese canine parvovirus 2C originated from dogs reveals a new Asia‐IV clade

“…These amino acid changes lead to the difference in two neutralizing antigenic sites on the surface of viral capsid (Allison et al., 2016; Hoelzer & Parrish, 2010; Stucker et al., 2012). Up‐to‐date, it is clearly showed that CPV‐2a spreads worldwide and is the key ancestor for the later variants, designated as CPV‐2b, CPV‐2c or new CPV‐2a, which are distributed variably (Voorhees et al., 2020). Current epidemiological surveys show that the CPV‐2a variant predominantly circulates in most Asia and in European countries while the CPV‐2b variant is a major antigenic variant in Iceland, the UK, the USA, Africa and some Asian countries (Clark et al., 2018).…”

“…After its emergence, CPV‐2c became widely distributed in other European and Latin American countries (Zhou, Zeng, Zhang, & Li, 2017). In recent years, CPV‐2c has spread many geographic regions and currently causes fatal disease in both domestic and wild dog populations (Aldaz et al., 2013; Decaro & Buonavoglia, 2012; Geng et al., 2015; Parthiban, Mukhopadhyay, Antony, & Pillai, 2010; Voorhees et al., 2020).…”