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.