Porcine circovirus type 4 (PCV4) is a novel virus associated with porcine dermatitis and nephropathy syndrome (PDNS)-like signs identified firstly in China in 2019. However, the details of the molecular epidemiology of PCV4 are unclear at this time. A total of forty-two related sequences were selected from the GenBank database to explore the spread of PCV4 and its rule in genetic evolution. Of the selected strains, 41 were from south China in 2019 to 2021 and the other was a foreign representative strain. Phylogenetic tree construction, nucleotide and amino acid (aa) sequence alignment, gene recombination and antigen structure prediction were performed on the collected sequences using bioinformatics softwares. The 42 PCV4 strains were divided into two subgenotypes: PCV4a (35/42) and PCV4b (7/42), according to the constructed genetic evolution tree. PCV4a is the main epidemic strain, and it can be further divided into two different gene clusters: PCV4a-1 (22/35) and PCV4a-2 (13/35). The pairwise comparison analysis showed that the complete genome sequence similarity of the 42 PCV4 strains ranged between 97.9% and 100%, and the aa sequences of the Cap proteins of 42 PCV4 strains had three major heterogenic or hypervariable regions—27–28, 96 and 212—all located near the antigenic epitope of the Cap protein. The results of this study can provide some basis for further studying the spread and epidemic growth of PCV4, and the prevention and control of PCV4 infection in China.
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