Beyond labels: current sequencing data do not support standardized porcine circovirus 3 (PCV3) genotypes.

Abstract

BACKGROUND: Porcine circovirus 3 (PCV3) has been detected worldwide in both healthy and diseased pigs, raising questions about its molecular diversity and potential genotype structure. Since its discovery, several genotyping schemes have been proposed; however, most of them rely on arbitrary criteria and often produce inconsistent or conflicting classifications. RESULTS: In this study, all high-quality PCV3 ORF2 sequences available at the GenBank to date were analyzed to evaluate whether consistent and reproducible genotyping criteria can be defined. Phylogenetic trees reconstructed using multiple algorithms and statistical comparisons of topological similarity revealed moderate-to-high incongruence among methods, limited phylogenetic signal, and a general decline in bootstrap support toward deeper nodes. Genetic distance distributions showed complete overlap between and within proposed genotypes, further questioning the biological meaning of such partitions. CONCLUSIONS: Overall, these findings indicate that the current genetic landscape of PCV3 does not support a robust or standardized genotyping framework. Given the low genetic variability of PCV3 and the absence of experimental evidence for genotype-specific differences in antigenicity, epidemiology, or virulence, the definition of formal genotypes appears challenging and premature, and likely unnecessary at this stage.