Porcine circovirus 2 (PCV-2) genotype update and proposal of a new genotyping methodology

Abstract

Porcine circovirus 2 (PCV-2) is one of the most widespread viral infections of swine, causing a remarkable economic impact because of direct losses and indirect costs for its control. As other ssDNA viruses, PCV-2 is characterized by a high evolutionary rate, leading to the emergence of a plethora of variants with different biological and epidemiological features. Over time, several attempts have been made to organize PCV-2 genetic heterogeneity in recognized genotypes. This categorization has clearly simplified the epidemiological investigations, allowing to identify different spatial and temporal patterns among genotypes. Additionally, variable virulence and vaccine effectiveness have also been hypothesized. However, the rapid increase in sequencing activity, coupled with the per se high viral variability, has challenged the previously established nomenclature, leading to the definition of several study-specific genotypes and hindering the capability of performing comparable epidemiological studies. Based on these premises, an updated classification scheme is herein reported. Recognizing the impossibility of defining a clear inter-cluster p-distance cut-off, the present study proposes a phylogeny-grounded genotype definition based on three criteria: maximum intra-genotype p-distance of 13% (calculated on the ORF2 gene), bootstrap support at the corresponding internal node higher than 70% and at least 15 available sequences. This scheme allowed defining 8 genotypes (PCV-2a to PCV-2h), which six of those had been previously proposed. To minimize the inconvenience of implementing a new classification, the most common names already adopted have been maintained when possible. The analysis of sequence-associated metadata highlighted a highly unbalanced sequencing activity in terms of geographical, host and temporal distribution. The PCV-2 molecular epidemiology scenario appears therefore characterized by a severe bias that could lead to spurious associations between genetic and epidemiological/biological viral features. While the suggested classification can establish a “common language” for future studies, further efforts should be paid to achieve a more homogeneous and informative representation of the PCV-2 global scenario.

Reservoirs of Porcine Circoviruses: A Mini Review

“…In late 1990s, a new porcine disease, called post-weaning multisystemic wasting syndrome (PMWS), emerged in North America and Europe (3)(4)(5)(6), and PCV2 was confirmed as the causal pathogen (7,8). PCV2 has a global distribution and diverse genotypes (9,10). In 2016, the third PCV, named PCV3, was discovered using high-throughput sequencing technology in U.S. swine herds suffering from porcine dermatitis and nephropathy syndrome (PDNS), reproductive failure and other syndromes (11,12).…”

Structural characterization of the PCV2d genotype at 3.3 Å resolution reveals differences to PCV2a and PCV2b genotypes, a tetranucleotide, and an N-terminus near the icosahedral 3-fold axes

“…Several phylogenetic studies have compared the amino acid sequence of PCV2 CPs to differentiate PCV2 into genotypes (6, 7, 14). Indeed, Franzo and Segales recently identified eight PCV2 genotypes (a-h) (14).…”

“…Several phylogenetic studies have compared the amino acid sequence of PCV2 CPs to differentiate PCV2 into genotypes (6, 7, 14). Indeed, Franzo and Segales recently identified eight PCV2 genotypes (a-h) (14). A report by Wang et al mapped the sequence variation in 50 PCV2 CP sequences onto the crystal structure and identified regions of variability (8); however, since then a significant number of CP sequences have been deposited into GenBank that requires revisiting the analysis.…”

“…Phylogenetic analysis of the PCV2 CP sequences has recently been used to identify eight genotypes (a-h) (14). We mapped the diversity and variability present in the CP sequences of the PCV2a, b, and d genotypes onto their respective atomic coordinates (Fig 6A-C) (9, 26).…”

“…reported and deposited a large quantity of PCV2d sequences into GenBank (5). Since then the number of PCV2d depositions in GenBank has significantly outpaced the deposition of PCV2b sequences (7, 14). The increase in the deposition of PCV2d sequences may be a result of PCV2d becoming an emerging and predominant genotype in Asia, Europe, North and South America.…”