Porcine Circovirus Type 4 Strains Circulating in China Are Relatively Stable and Have Higher Homology with Mink Circovirus than Other Porcine Circovirus Types

Abstract

Porcine circovirus type 4 (PCV4) is a newly identified porcine circovirus (PCV) belonging to the Circovirus genus Circoviridae family. Although several groups have conducted epidemiological investigations on PCV4 and found that PCV4 also exists widely in pigs, there are few reports on the origin and evolution of PCV4. In this study, the genetic relationship between PCV4, mink circovirus (MiCV), bat circovirus (BtCV), PCV1, PCV2, and PCV3 was analyzed, and the consistency of viral proteins in three-dimensional (3D) structure and epitopes was predicted. We found that the genome and protein structure of PCV4 was relatively stable among current circulating PCV4 strains. Furthermore, PCV4 was more similar to MiCV in terms of its genome, protein structure, and epitope levels than other PCVs and BtCVs, suggesting that PCV4 may be derived from MiCV or have a common origin with MiCV, or mink may be an intermediate host of PCV4, which may pose a great threat to other animals and/or even human beings. Therefore, it is necessary to continuously monitor the infection and variation of PCV4, analyze the host spectrum of PCV4, and establish the prevention and treatment methods of PCV4 infection in advance.

Advances in Crosstalk between Porcine Circoviruses and Host

“…Although the pathogenesis of PCV, especially PCV3 and PCV4, remains to be clarified, the widespread distribution of PCV2, PCV3, and PCV4 in pigs (including diseased and healthy pigs), wild boar, and/or other animals has been confirmed [ 3 , 4 , 15 , 16 , 17 , 18 , 19 ]. Notably, both PCV2 and PCV3 are closely related to bat circovirus in genome and protein levels, whereas PCV4 has higher homology to mink circovirus [ 1 , 3 , 20 ], which suggests that the host spectrum of PCVs may be broader than what we have already determined. Therefore, it is still urgent and necessary to prevent and control the transmission and infection of PCVs in pigs, which depends on an in-depth understanding of the interaction between the virus and the host.…”

“…PCVs are non-enveloped DNA viruses with a diameter of about 20 nm, belonging to the genus Circovirus in the family Circoviridae [ 1 , 2 , 3 , 4 ]. The genome of PCV is a single-stranded, positive-circular DNA of about 1.7–2.0 kb in length, encoding structural protein capsid (Cap), replicase (Rep), and/or other non-structural proteins ( Figure 1 A) [ 1 , 2 , 3 , 4 ]. The genome of PCV2 contains at least 11 open reading frames (ORFs), of which five ORFs encode proteins with known or partially known functions.…”

“…In addition, the ORF5 protein can induce autophagy, endoplasmic reticulum stress (ERS), unfolded protein response (UPR), and circumvent host immune surveillance, thus enhancing virus replication [ 27 , 28 , 29 , 30 ]. Up to now, only three ORFs in PCV3 (ORF1, ORF2, and ORF3) and two ORFs in PCV4 (ORF1 and ORF2) have been identified [ 1 , 15 ]. The functions of the proteins encoded by these ORFs are similar to those of the corresponding proteins in PCV2 [ 1 , 15 ].…”

“…Up to now, only three ORFs in PCV3 (ORF1, ORF2, and ORF3) and two ORFs in PCV4 (ORF1 and ORF2) have been identified [ 1 , 15 ]. The functions of the proteins encoded by these ORFs are similar to those of the corresponding proteins in PCV2 [ 1 , 15 ].…”

“…Porcine circoviruses (PCVs) are viruses isolated from diseased pigs or porcine cells, which include PCV1 to PCV4 to date [ 1 , 2 , 3 , 4 ]. PCV1 was first identified and isolated from porcine kidney cells and considered contamination due to its non-pathogenic characteristics in vivo and in vitro [ 5 ].…”