Introduction
Canine parvovirus (CPV-2), a causative agent of hemorrhagic gastroenteritis and myocarditis in canids, belongs to the family Parvoviridae, subfamily Parvovirinae, and genus Protoparvovirus(Maclachlan et al., 2011). The clinical symptoms include fever, leukopenia, diarrhea, dehydration, anorexia with 100% morbidity, and mortality of 10% in adult dogs and 91% in pups(Nandi et al., 2019).
CPV-2 is a naked, icosahedral, linearized, and single-stranded DNA virus(Cavalli et al., 2018). The capsid consists of 60 subunits. Each subunit has the same eight-stranded antiparallel β-barrel motif with large insertions between strands of the β-barrel(Parrish, 2010). The features of capsid include spikes in the three-fold axes, a canyon-like depression circulating around each of the five-fold axes, and a dimple-like depression at the two-fold axes(Agbandje and Rossmann, 1995). The full genome is 5323bp, containing two open reading frames (ORFs). One is located in 3’, encoding nonstructural proteins called NS1 and NS2. NS1 is necessary for duplicating(Maclachlan et al., 2011) while the function of NS2 is still unclear, which seems not required for efficient replication and assembly(Wang et al., 1998). Another ORF is located in 5’, which encodes structural protein including VP1 and VP2 through alternative splicing of the same mRNAs. VP1 protein contains the complete sequence of VP2 protein and a 143 residues unique N-terminal sequence required for successful infection(Vihinen-Ranta et al., 2002). The VP2 protein is a favored location for mutation and a key molecule determining the host range, antigenic properties, and receptor binding. The antigens or subtypes of CPV-2 can be identified by certain residues positioned within the VP2 protein(Vannamahaxy and Chuammitri, 2017). VP3 was derived from VP2 protein by host proteolytic cleavage presenting only on complete (DNA-containing) virions(Nandi and Kumar, 2010).
CPV-2 was regarded as a host-range variant derived from an FPLV-like virus via wild carnivores that gained the ability to bind the canine transferrin receptors (TfR), thus allowing the infection of dogs while failed to replicate in the feline host (Hueffer et al., 2003; Nandi et al., 2019; Stucker et al., 2012). CPV-2 was first reported in 1978 in the United States whereas the serological test indicated that dogs in Europe or Eurasia were widely infected between 1974 and 1976(Hoelzer and Parrish, 2010). At least six amino acid differences between CPV-2 and FPLV were found. VP2 amino acid residues 93 and 323 determined the canine host range(Chang et al., 1993). Within a few years, its variants arose and replaced the original CPV-2. The first CPV-2 variant, termed CPV-2a, emerged in 1979. The single mutation of VP2 residue 300, from Asp to Gly, is a key determinant of infecting cats(Organtini et al., 2015). In 1984 and 2001, another two variants, CPV-2b and CPV-2c were detected in the United States and Italy respectively. Antigenic differences among these three variants were based on the amino acid presented at residue 426 of VP2 protein (Asn in CPV-2a, Asp in CPV-2b and Glu in CPV-2c)(Miranda and Thompson, 2016).
Additional variants, New CPV-2a and New CPV-2b, were discovered in 1990. They differ from CPV-2a/b only at 297 residue (Ser to Ala) of VP2 protein without changing their antigenic properties even its proximity to epitope B(Ohshima et al., 2008), which is currently detected in most recent CPV-2 strains(Martella et al., 2006). Another two variants, CPV-2c(a) and CPV-2c(b), were isolated from Vietnamese leopard cats in 1997 with substitution at residue 300 (Gly to Asp) and lost canine host range(Ikeda et al., 2000; Ohshima et al., 2008). The few amino acid differences in VP2 protein between FPLV, CPV-2 and, CPV-2 variants appear to have modified important biological properties, such as antigenic properties, host ranges, interactions with TfR, and virulence(Cavalli et al., 2008).
In China, the first CPV-2 case was detected in 1982(Shizhe et al., 1982). CPV-2 prevailed during the early 1980s, then it was gradually replaced by CPV-2a after 1986(Zhijing et al., 2004). In the 1990s, most CPV-2 variants detected were New CPV-2a/2b, which seemed to completely replace CPV2a/2b. The New CPV-2a has been the dominant genotype since the 1990s. After 2000, the detection rate of New CPV-2b increased, which was identified as the dominant strains in some cities(Jianqing, 2003; Kegong et al., 2004; Zhijing et al., 2004). The CPV-2c variant was observed initially in 2009 and has developed a continuous uptrend since 2010(Qi et al., 2020). In this study, we collected samples in the Tianjin area, a city that hasn’t been investigated before, along with other cities between 2018 and 2020. To further study the prevalence of CPV-2 in China, we retrieved CPV-2 sequences date with clear background collected in China from Genbank and related papers from 2014 to 2019 then examined those data in detail.