Towards a unified nomenclature for diseases associated with porcine circovirus infections

PORCINE circoviruses (PCVs) are small, circular, single-stranded DNA viruses belonging to the genus Circovirus within the family Circoviridae. As of 2024, there were four recognised species (PCV1 to PCV4),1 with a potential fifth species (PCV5) recently reported in pigs in China.2 Since their discovery,3, 4 PCVs have represented a remarkable example of viral diversity and disease evolution. PCV1 was first identified in the 1970s as a non-pathogenic cell culture contaminant, although it has since been found that subclinical infections are common in pigs worldwide.5, 6 In contrast, PCV2 was linked to a new condition known as postweaning multisystemic wasting syndrome (PMWS) in the mid-1990s.7-9 Despite early controversy regarding causality – mainly due to the disease's multifactorial nature and inconsistent reproduction in experimental models – the subsequent global success of PCV2 vaccines confirmed the pathogenic role of the virus. Indeed, PCV2 is now recognised as a major pathogen of pigs, responsible for systemic and reproductive disorders, subclinical infection with loss of average daily weight gain, and porcine dermatitis and nephropathy syndrome (PDNS).10 PCV3, discovered in 2016 using next-generation sequencing, has also been associated with clinical disease, and was initially detected in pigs with reproductive failure, systemic inflammation and lesions reminiscent of PDNS.11, 12 Meanwhile, although PCV4, identified in 2020,13 and the putative PCV52 have been detected in both diseased and healthy pigs, their pathogenicity remains unclear. However, it is important to note that only PCV1 and PCV2 can be readily cultured,14 with the isolation of PCV3 being limited to a few laboratories, and neither PCV4 nor PCV5 having yet been propagated in vitro. Before 2015, the terminology for PCV-associated conditions was relatively simple. PCV1 was non-pathogenic, while PCV2 was associated with PMWS,7-9 reproductive disorders15 and PDNS,16 with reduced growth rates linked to subclinical infection.17 Early reports also connected PCV2 with respiratory and enteric disease, but later studies clarified that systemic infection was the unifying pathogenic feature.18, 19 To harmonise terminology, the term porcine circovirus diseases (PCVD) was proposed in 2002.20 This terminology was accepted in Europe; however, in North America, it was felt that any new term used in connection with PCV2 should include the word ‘associated’. Thus, the term porcine circovirus-associated disease (PCVAD) was coined by the American Association of Swine Veterinarians in March 2006.21 Unfortunately, the use of PCVAD in America and Asia and PVCD in Europe often resulted in the existence of two names for the same condition, which resulted in considerable confusion.22 A further step in 201210 refined the classification of PCV2-associated conditions into three main entities: PCV2-systemic disease (PCV2-SD) – replacing PMWS, characterised by wasting and lymphoid cell depletion; PCV2-reproductive disease (PCV2-RD) – encompassing fetal infection, abortion and stillbirth; and PCV2-subclinical infection (PCV2-SI) – associated with reduced growth and production losses without overt clinical signs (Table 1). However, the term PDNS was maintained, as it is regarded as an immune-complex disease in which PCV2 was considered the associated antigen based on circumstantial evidence, since it has never been experimentally reproduced.21 The discovery of new PCV species has further complicated disease nomenclature. PCV3, initially associated with reproductive failure, systemic inflammation and PDNS-like lesions, shared clinical overlap with PCV2 but exhibited distinct histopathological features.11, 12 An experimental infection study proposed that PCV3-reproductive disease (PCV3-RD) and PCV3-systemic disease (PCV3-SD) may represent sequential manifestations of a single pathogenic process.23 Accordingly, the collective term PCV3-associated diseases (PCV3-AD) was introduced to encompass both conditions.24 PCV5 has been reported only once,2 with minimal clinical description and debatable histological evidence. Its aetiological role remains speculative; thus, any discussion of case definitions or disease terminology should await further confirmation. Since the initial identification of PCV1 nearly 50 years ago, the Circovirus genus has expanded substantially. Yet, as viral taxonomy has evolved, disease terminology has lagged behind, often resulting in inconsistent use and miscommunication. The establishment of standardised, universally accepted nomenclature is therefore critical to ensure consistency in diagnosis, surveillance and research. This framework ensures adaptability for future discoveries while maintaining internal consistency. When considering disease nomenclature, PDNS deserves particular attention. Up to three PCV species (PCV2, PCV3 and PCV4) have been linked to this condition; however, experimental reproduction has never been successful. The association with PCV2 is largely circumstantial but is strongly supported by three main observations: PDNS emerged concurrently with PCV2-SD, affected pigs exhibit high PCV2 antibody titres and the implementation of PCV2 vaccination led to a dramatic decline in PDNS incidence. PDNS's associations with PCV3 and PCV4 are weaker, being limited to sporadic PCR detections in cases that often do not fit the classical diagnostic criteria. Indeed, a recent investigation confirmed the presence of PCV2 antigen and/or nucleic acid in all examined PDNS cases. In contrast, PCV3 was detected in only about 30 per cent of cases, while PCV4 was not detected at all.27 Based on this evidence, we suggest that PDNS should continue to be classified as a PCV2-associated disease. PCVs represent one of the most dynamic and evolving viral groups recognised in veterinary medicine. From the recognition of PCV1 as a harmless contaminant to the recent discovery of new species such as the putative PCV5, our understanding of their taxonomy and pathogenic potential has greatly expanded. However, the lack of unified terminology has hampered clear communication and data comparability. The nomenclature proposed here – anchored on the global concept of PCV-associated diseases – provides a coherent and flexible framework capable of accommodating future discoveries and supporting consistent application across research, diagnostics and industry.