Holgado-Martín Rocío, Gómez Luis, Risco David, Martínez Remigio, García-Sánchez Alfredo, Legnardi Matteo, Franzo Giovanni
Department of Animal Medicine, Area of Anatomy and Pathological Anatomy, University of Extremadura 10003, Cáceres, Spain.
Department of Animal Health, Animal Health and Zoonosis Research Group (GISAZ), UIC Zoonosis and Emerging Diseases (ENZOEM), University of Córdoba 14014, Córdoba, Spain.
Transbound Emerg Dis. 2025 Jul 22;2025:9326570. doi: 10.1155/tbed/9326570. eCollection 2025.
Porcine circovirus 4 (PCV4) was first identified in China in 2019 and retrospectively traced back to 2008. However, unlike other circoviruses, its distribution appeared to be largely confined to Asian countries until recent reports from Spain and the United States. This study aims to enhance knowledge of the past and present circulation of PCV4 in non-Asian countries, particularly in Spain and in wild boars, where it was previously detected at a significant prevalence. By genetically characterizing the strains, the contextualization within both national and international epidemiological frameworks was attempted. A total of 302 lymph node samples were tested, with 62 testing positives by quantitative real-time polymerase chain reaction (qPCR), predominantly from the 2011 to 2015 period, although five positives were detected in the 2022-2024. Complete open reading frame 2 (ORF2) sequences were obtained from 10 strains. Phylogenetic analysis revealed two major clusters: one comprising only Chinese sequences and another containing strains from multiple continents, including Spain and the United States. The Spanish strains formed a distinct monophyletic clade whose introduction in the country was estimated through phylodynamic analyses around 2000, suggesting long-term undetected circulation. Within Spain, a progressive geographical spread and strain exchange between wild boars and outdoor reared domestic pigs could be inferred. On the other hand, the lack of detection in intensively raised pigs, at least in Europe, remains unclear. The present findings extend the current knowledge of PCV4 history outside Asia and challenge the paradigm of a recent international spreading. Recognizing the current uncertainties in PCV4's international distribution and epidemiology, further efforts are needed, including the use of archived samples in diagnostic activities as well as the sharing of negative results.
猪圆环病毒4型（PCV4）于2019年在中国首次被发现，并追溯至2008年。然而，与其他圆环病毒不同的是，在西班牙和美国最近报告之前，其分布似乎主要局限于亚洲国家。本研究旨在增进对PCV4在非亚洲国家，特别是在西班牙和野猪中过去和当前传播情况的了解，此前在这些地方已检测到该病毒具有较高的流行率。通过对毒株进行基因特征分析，试图将其置于国家和国际流行病学框架中进行背景分析。共检测了302份淋巴结样本，其中62份通过定量实时聚合酶链反应（qPCR）检测呈阳性，主要来自2011年至2015年期间，不过在2022 - 2024年期间也检测到5份阳性样本。从10个毒株中获得了完整的开放阅读框2（ORF2）序列。系统发育分析揭示了两个主要聚类：一个仅包含中国序列，另一个包含来自多个大陆的毒株，包括西班牙和美国。西班牙的毒株形成了一个独特的单系分支，通过系统发育动力学分析估计其于2000年左右传入该国，这表明该病毒长期未被检测到而一直在传播。在西班牙境内，可以推断出野猪和户外饲养的家猪之间存在渐进的地理扩散和毒株交换。另一方面，至少在欧洲，集约化养殖的猪中未检测到该病毒的原因仍不清楚。目前的研究结果扩展了我们对PCV4在亚洲以外地区历史的现有认识，并挑战了近期国际传播的范式。鉴于目前PCV4国际分布和流行病学存在的不确定性，需要进一步努力，包括在诊断活动中使用存档样本以及分享阴性结果。
