Data Sheet 1_An updated phylogeography and population dynamics of porcine circovirus 2 genotypes: are they reaching an equilibrium?.zip

IntroductionPorcine circovirus 2 (PCV2) emerged more than three decades ago as one of the most impactful pathogens in the swine industry. Despite being a DNA virus, one of the hallmarks of PCV2 is its high evolutionary rate, which has led to the emergence of different genotypes, each exhibiting varying degrees of evolutionary success. Current knowledge suggests the occurrence of three main waves of genotype dominance, alternating over time (i.e., PCV2a, PCV2b, and PCV2d), alongside less prevalent genotypes. However, although PCV2d is currently the most common genotype nowadays, the others continue being circulating in the pig population.MethodsThe present study reconsidered the epidemiological and evolutionary patterns of PCV2 genotypes using phylodynamic analyses, benefiting from an almost 10-fold increase in ORF2 sequence availability compared to previous studies. Additionally, a phylogeographic analysis was performed to investigate viral dispersal patterns and frequency, and the selective pressures acting on the capsid protein were estimated and compared among genotypes.ResultsWhile successive emergence of major genotypes was confirmed, this study extends previous findings by revealing subsequent prevalence fluctuations of PCV2a and PCV2b after their initial decline. This evolutionary process may represent an example of balancing selection, specifically negative frequency-dependent selection, where a genotype fitness diminishes as it becomes more common, and vice versa. Variations in genotype- or clade-specific immunity—affected by the local prevalence of viral groups—combined with the periodic introduction of strains that have independently evolved in different regions, may have led to fluctuations in the population dynamics of major genotypes over time. These fluctuations were associated with ongoing evolution and variations in the capsid amino acid profile.DiscussionThese findings have profound implications for future control strategies. Although PCV2d remains the most prevalent and widespread genotype, other genotypes should not be neglected. Control strategies should thus target the entire PCV2 population, with a focus on fostering broader and more cross-protective immunity.

猪圆环病毒2型（PCV2）自三十多年前出现以来，已成为养猪业最具影响力的病原体之一。尽管其为DNA病毒，但PCV2的一个显著特征是其高进化速率，这导致了不同基因型的出现，每种基因型均展现出不同程度的进化成功率。当前的研究表明，三种主要基因型（PCV2a、PCV2b和PCV2d）的流行波次依次交替出现（即随时间交替出现），同时伴随着其他较少见的基因型。然而，尽管PCV2d目前是最常见的基因型，但其他基因型仍在猪群中持续流行。本研究重新审视了PCV2基因型的流行病学和进化模式，利用了与先前研究相比序列可用性增加近十倍的优势。此外，还进行了系统地理分析，以调查病毒的传播模式和频率，并对基因型之间作用的囊膜蛋白的选择压力进行了估算和比较。结果显示，尽管主要基因型的连续出现得到了证实，但本研究通过揭示PCV2a和PCV2b在其初始下降后的后续流行波动，扩展了先前的研究发现。这一进化过程可能代表了一种平衡选择，特别是负频率依赖性选择，其中基因型的适应度随着其变得更为普遍而降低，反之亦然。基因型或分支特异性免疫力的变化——受病毒组地方流行率的影响——以及不同地区独立进化的菌株的周期性引入，可能导致了主要基因型种群动态随时间的变化。这些波动与持续进化和囊膜氨基酸谱的变化相关。讨论中提到，这些发现对未来控制策略具有深远的影响。尽管PCV2d仍然是普遍和广泛传播的基因型，但其他基因型不应被忽视。因此，控制策略应针对整个PCV2群体，重点关注培养更广泛和更具交叉保护性的免疫力。