Porcine Circovirus Background

Circoviruses are widely distributed in mammals, fish, avian species and insects. In pigs, four different CVs have been identified and named with consecutive numbers based on the order of their discovery: Porcine circovirus 1 (PCV1), Porcine circovirus 2 (PCV2), Porcine circovirus 3 (PCV3) and Porcine circovirus 4 (PCV4). The PCV genome is one of the simplest of all viruses, requiring only a capsid protein (ORF2) and two replicase proteins (ORF1) in order to replicate and produce a functional virus. The viral capsid is icosahedral and approximately 17 nm in diameter. PCV infects a wide variety of cell types, including hepatocytes, cardiomyocytes, and macrophages via clathrin-mediated endocytosis, although there may also be other entry factors that haven’t yet been identified.

PCVs were originally identified in 1974 when a novel, noncytopathogenic, picornavirus-like contaminant in the porcine kidney cell line PK-15 was discovered. It was shown to be a small, nonenveloped virus containing a single-stranded, circular DNA genome and was named porcine circovirus (PCV). PCV antibodies in swine were found to be widespread, and experimental infections with this virus in pigs did not result in clinical disease, suggesting that this PCV was nonpathogenic.

Later, during the early and mid-1990s a new disease was described in Western Canada, namely postweaning multisystemic wasting syndrome (PMWS, now PCVAD). In the late 1990s, a novel PCV-like virus was isolated from PMWS-affected pigs which was antigenically and genetically distinct from the PK-15 cell culture PCV contaminant. These new PCV isolates were designated as porcine circovirus type 2 viruses (PCV2) and the original PCV from PK-15 cell cultures as porcine circovirus type 1. PCV2 has been associated with PMWS or systemic disease, respiratory disease, enteric disease, reproductive disease and porcine dermatitis and nephropathy syndrome (PDNS) (Ouyang et al., 2019). Phylogenetic studies have shown that at least three genotypes of PCV2 exist (PCV2 a, b, and c). PCV2 infections may downregulate the host immune system and enhance the infection and replication of other pathogens and swine that show signs of PCV2-SD usually are infected with multiple agents, including porcine parvovirus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, Staphylococcus spp, and Streptococcus spp.

PCV-3 was described in 2016, causes a wide range of problems, and may be widespread among pigs. It is associated with porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs, reproductive failure, and cardiac and multiorgan inflammation. Furthermore, PCV3 has been detected in other animals and ticks, suggesting that PCV3 possesses cross-species transmission abilities and has broad distribution and circulation in the wild (Ouyang et al., 2019). The role of PCV3 is still controversial and propagation is challenging, limiting studies on it. Both PCV-1 and PCV-2 show a high degree of sequence identity and similar genomic organization, whereas the PCV-3 sequence identity is much lower, despite similar organization (Opriessnig et al., 2020).

PCV4 was identified in 2016, with the aid of sequencing, in 7 and 12 week old pigs suffering from respiratory, enteric and PDNS signs and also in healthy pigs from two farms in Hunan province, China. The distribution of PCV4 is currently unknown.

Generally, PCV2 vaccines have been shown to be very successful and efficacious but in the future additional PCV3 and PCV4 vaccines may be needed by global pig producers (Opriessnig et al., 2020).

References

• Ellis J. Porcine circovirus: a historical perspective. Vet Pathol. 2014 Mar;51(2):315-27.
• Opriessnig T, Karuppannan AK, Castro AMMG, Xiao CT. Porcine circoviruses: current status, knowledge gaps and challenges. Virus Res. 2020 Sep;286:198044.
• Ouyang T, Zhang X, Liu X, Ren L. Co-Infection of Swine with Porcine Circovirus Type 2 and Other Swine Viruses. Viruses. 2019 Feb 21;11(2):185.
• Ouyang T, Niu G, Liu X, Zhang X, Zhang Y, Ren L. Recent progress on porcine circovirus type 3. Infect Genet Evol. 2019 Sep;73:227-233.
• Segalés J. (2014). Overview of Porcine Circovirus Diseases. MSD Veterinary Manual.