**2. Virology of CPV-2**

Canine parvovirus infection is caused by *Carnivore protoparvovirus-1* which is characterized under the genus *Protoparvovirus*, family *Parvoviridae*. CPV-2 is a member of the *Parvoviridae* family, which includes two subfamilies: *Parvovirinae* (infects vertebrates) and *Densovirinae (infects invertebrates) Parvovirus, Erythrovirus, Dependovirus, Amdovirus, Bocavirus,* and other unclassified vertebrate parvoviruses are all the genus which comes under *Parvovirinae* (**Figure 1**) [16]. CPV-2 genome is a single stranded, negative sense, linear DNA of about 5 kb [17] contained by two ORFs translated into 4 proteins through alternative splicing [18, 19]. One ORF is associated with the nonstructural proteins NS1 and NS2, which are mainly related to the viral replication and

**Figure 1.** *Schematic representation of* Parvovirdae *taxonomy.* *Canine Parvovirus-2: An Emerging Threat to Young Pets DOI: http://dx.doi.org/10.5772/intechopen.104846*

the second ORF is related with the viral capsid constituents VP1 and VP2. After the cleavage of VP2, VP3 is formed due to the involvement of host proteases. The capsid has 60 protein subunits, 90% of which are VP2 (67 kDa) and 10% are VP1 (83 kDa) [20].

The virus is nonenveloped having icosahedral symmetry and is 25 nm in diameter. The CPV virus is made up of the sixty protein subunits containing VP1 (5–6 units) and VP2 (54–55 units). The protein structure is made up of antiparallel β-barrel (8-stranded) capsid. The viral replication occurs inside the nucleus of multiplying cells and therefore the intranuclear inclusion bodies are formed during the infection. The viral capsid structure is made up of spike at the three-fold axes of the icosahedral unit, a 15-Å depression around the five-fold axes and two-fold axes is formed. Antigenic determinant regions have been plotted to the three-fold protrusion and the two-fold depression are related to the host cell features [17]. The surface of the capsid is composed of four loops inserted between the strands, resulting in spike-like protrusions around threefold axes of approximately 22 Å. The antigen neutralization site, also known as epitope A, is composed of loops 1 and 2 of one VP2 and loop 4 of a threefold related molecule [21]. The molecular weight (MW) is around 5.5 to 6.2 × 106 Da. There is an equal ratio of protein to nucleic acid.

NS1 is the largest non structural protein in CPV-2, and it is primarily involved in viral replication and pathogenicity [22]. NS1 is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis by inducing an antitumor immune response in different tumor models [23]. A recent study demonstrated the amino acid residues of T598 and T601 in the C-terminal phosphorylation sites of NS1 protein, involved in replication and pathogenicity of CPV-2 [24].

In the 1970s, CPV-2 emerged as a novel pathogen in dogs. Since then, CPVE has been reported across all the continents [25, 26]. Other related viruses such as Feline panleukopenia virus (FPV), Mink enteritis virus (MEV), Raccoon parvovirus (RPV) are closely related to the CPV-2 [27]. Mutations in the canine transferrin receptor (TfR) type-1 lead to adaptation of CPV-2 in different species 2 [28, 29]. There is more than 98% genome homology reported in the CPV and FPV nonetheless infect different species and have typical antigenic capsid and haemagglutination (HA) properties [28, 30]. The mutations in different amino acid positions have led to the effective adaptation in the new hosts [30]. There are over five to six mutations in the VP2 residue of the CPV-2 and FPV and also 375 and 323 amino acid position regulates the pH functionality of HA [31, 32]. CPV-2a (Asn CPV-2a) replaced CPV 2 in 1980s in the USA and various European countries. CPV 2a can infect the cats which was not a feature of CPV 2. CPV 2a has been displaced by the CPV-2b (426Asp) which was first reported in USA in 1982 and CPV-2c (426Glu) variant in Italy [31, 33]. Although two variants, CPV-2a and 2b had been identified much earlier, however, the third variant CPV-2c had been recognized in early 2000 [33]. Thereafter it has been reported frequently from many different countries. In addition, new CPV-2a and new CPV-2b have also been documented due to non-synonymous substitution at 297 residues (Ser to Ala) of VP2 protein [34]. In India, CPV-2a has recently become the most prevailing antigenic type among all variants. Recent emergence of new antigenic variants that differ significantly from the current vaccine strains is a matter of concern for efficacy of vaccine [35].
