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We identified a novel human circovirus in an immunocompromised 66-year-old woman with sudden onset of self-limiting hepatitis. We detected human circovirus 1 (HCirV-1) transcripts in hepatocytes and the HCirV-1 genome long-term in the patient's blood, stool, and urine. HCirV-1 is an emerging human pathogen that persists in susceptible patients.

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.

Porcine circovirus type 2 (PCV2) plays a key role in PCV2-associated disease (PCVAD) etiology and has yielded significant losses in the pig husbandry in the last 20 years. However, the impact of two recently described species of porcine circoviruses, PCV3 and PCV4, on the pork industry remains unknown. The presence of PCV3 has been associated with several clinical presentations in pigs. Reproductive failure and multisystemic inflammation have been reported most consistently. The clinical symptoms, anatomopathological changes and interaction with other pathogens during PCV3 infection in pigs indicate that PCV3 might be pathogenic for these animals and can cause economic losses in the swine industry similar to PCV2, which makes PCV3 worth including in the differential list as a cause of clinical disorders in reproductive swine herds. Moreover, subsequent studies indicate interspecies transmission and worldwide spreading of PCV3. To date, research related to PCV3 and PCV4 vaccine design is at early stage, and numerous aspects regarding immune response and virus characteristics remain unknown.

Porcine circovirus type 2 (PCV2) is an economically important swine pathogen and, although small, it has the highest evolution rate among DNA viruses. Since the discovery of PCV2 in the late 1990s, this minimalistic virus with a 1.7 kb single-stranded DNA genome and two indispensable genes has become one of the most important porcine pathogens, and presently is subjected to the highest volume of prophylactic intervention in the form of vaccines in global swine production. PCV2 can currently be divided into five different genotypes, PCV2a through PCV2e. It is well documented that PCV2 continues to evolve, which is reflected by changes in the prevalence of genotypes. During 2006, commercial vaccines for PCV2 were introduced on a large scale in a pig population mainly infected with PCV2b. Since 2012, the PCV2d genotype has essentially replaced the previously predominant PCV2b genotype in North America and similar trends are also documented in other geographic regions such as China and South Korea. This is the second major PCV2 genotype shift since the discovery of the virus. The potential increase in virulence of the emergent PCV2 genotype and the efficacy of the current vaccines derived from PCV2a genotype against the PCV2d genotype viruses has received considerable attention. This review attempts to synthesize the understanding of PCV2 biology, experimental studies on the antigenic variability, and molecular epidemiological analysis of the evolution of PCV2 genotypes.

Circoviruses (family Circoviridae) are small, single-stranded DNA viruses known to infect a broad range of bird species. The Beak and Feather Disease Virus (BFDV), typically associated with parrots, has occasionally been reported in unrelated avian taxa, raising questions about host range and potential spillover. We investigated BFDV-like sequences in three sympatric vultures breeding in Spain (Egyptian vulture Neophron percnopterus, cinereous vulture Aegypius monachus, and griffon vulture Gyps fulvus). PCR screening revealed low and inconsistent prevalence in Egyptian vultures (7.4%, n = 163) and cinereous vultures (2.9%, n = 47), and absent in griffon vultures (n = 35). Phylogenetic analyses identified nine highly divergent haplotypes spanning three distinct clades, with no structure by species, geography, or year, and no evidence of nest- or territory-level transmission. These patterns contradict expectations for an actively circulating virus and instead suggest that the sequences represent endogenous circoviral elements (ECV) integrated into the host genome. The absence of clinical signs, except in one inbred Egyptian vulture nestling (offspring of a brother-sister mating), indicates these elements are non-pathogenic. Our findings demonstrate that BFDV detections in non-psittacine birds often reflect genomic remnants rather than active infections. This reinterpretation underscores the need to combine molecular surveillance and evolutionary genomics to distinguish actual infections from viral relics.

Porcine circovirus-associated disease encompasses multiple disease syndromes including porcine circovirus 2 systemic diseases, reproductive failure, and porcine dermatitis and nephropathy syndrome. Until recently, porcine circovirus 2 was the only species associated with the porcine circovirus-associated disease. In this report, diagnostic investigations of thirty-six field cases submitted from multiple production systems, numerous sites and varied geographic locations demonstrated porcine circovirus 3 within lesions by in situ hybridization including fetuses with myocarditis, weak-born neonatal piglets with encephalitis and myocarditis, from cases of porcine dermatitis and nephropathy syndrome, and in weaned pigs with systemic periarteritis. Porcine circovirus 3 was detected by PCR in numerous fetuses and perinatal piglets at high viral loads (trillions of genome copies per mL of tissue homogenate). Samples from all cases in this study were assayed and found negative for porcine circovirus 2 by PCR. Metagenomic sequencing was performed on a subset of reproductive cases, consisting of sixteen fetuses/fetal sample pools. PCV3 was identified in all pools and the only virus identified in fourteen pools. Based on these data, porcine circovirus 3 is considered a putative cause of reproductive failure, encephalitis and myocarditis in perinatal piglets, porcine dermatitis and nephropathy syndrome, and periarteritis in swine in the United States.

Circovirus human is a new viral species that includes the human circovirus (HCirV), which has been linked to hepatitis in immunocompromised persons. We investigated prevalence of HCirV infection in 278 patients with hepatitis and 184 asymptomatic persons using real-time PCR and sequencing assays. HCirV viremia and sequences were found in 8 (2.9%) hepatitis patients and no asymptomatic patients. Alternate causes of hepatitis (hepatitis E and cholangitis) were clearly identifiable in 2 HCirV-infected patients. HCirV could not be ruled out as a contributor to hepatitis in the remaining 6 patients, 4 of whom were immunocompromised. Persistent infections were documented in 3 patients, but only 1 had relapsing hepatitis. One HCirV patient displayed symptoms of an infectious mononucleosis-like syndrome. Isolates clustered with known HCirV strains from France and China. HCirV-derived virus-like particles bound to PLC/PRF/5 and Hep-G2 human hepatoma cells but not to lung epithelial cells, indicating hepatic tropism.

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated diseases in swine and is also described as the modulator of host immunity that exacerbates the clinical outcome of many bacterial and viral infections. To date, it has caused increasingly larger losses in the pig industry worldwide. The genomic DNA of PCV2 is predicted to contain 11 open reading frames (ORFs) and at least seven potential ORFs-encoding proteins larger than 5 kDa. Currently, however, only five virally encoded proteins (Rep, Rep′, Cap, ORF3, and ORF4 protein) have been identified in PCV2 replication. In the present review, we strive to discuss the current understanding of the genomic DNA of PCV2 with the purpose of providing insight into the scientific basis of the pathogenesis of PCV2 and the prevention of its infection.

Recently, the emergence of HP-PRRSV (Highly Pathogenic porcine reproductive and respiratory syndrome virus) and the exacerbation of mixed infections of PRRSV and PCV have resulted in significant economic losses for the Chinese pig industry. This study collected a total of 226 samples suspected of infection with the aforementioned viruses from diverse pig farms in seven urban districts of central and northern Guangdong Province between 2020 and 2022. The positive rates of PRRSV, PCV2, and PCV3 in the samples were 33.2%, 37.6%, and 7.5%, respectively, and there were various mixed-infection scenarios present in the samples. This study successfully isolated multiple strains of PRRSV2 and PCV2 from their positive samples, and obtained the gene sequences of six PCV3 (ORF1 + ORF2) from samples. The associated sequences obtained were subjected to bioinformatic analysis and revealed the following:Predominantly prevalent strains of PRRSV in Guangdong Province include HP-PRRSV and NADC30-like variants, whereas PCV2 is primarily represented by the 2b and 2d subtypes. Specifically, the amino acid variation patterns exhibited by the PRRSV GP5 and NSP2 proteins of the strains sg_2108, qy_2008, and fs_2108 under environmental selective pressure are remarkably similar to the characteristics of Highly Pathogenic PRRSV; thus, it is inferred that they may possess higher virulence. The detected PCV3 strains were predominantly concentrated within the PCV3a-IM branch. All PRRSV strains involved in this study are wild-type-PRRSV (wt-PRRSV), comprising three recombinant strains and seven highly virulent strains. Among these strains, the ORF1a gene exhibited the highest variability in their genomes. Environmental selective pressure may enhance the virulence and immune evasion capabilities of PRRSV and drive mutations in the Cap proteins of PCV2 and PCV3. Conversely, PCV2 and PCV3 strains demonstrated greater stability in genetic evolution. In conclusion, this study enhances the epidemiological data regarding PRRSV, PCV2, and PCV3 in Guangdong Province, China, and is significant for the surveillance, prevention, and active control of these three diseases.

This study describes the genetic and antigenic characterization of a newly emerging porcine circovirus type 2b (PCV2b) mutant first isolated in cases of vaccine failure in Korea. The full genome of the PCV2b isolates (SNUVR130689 and SNUVR140004) is 1,767 base pairs (bp) in length. The size of ORF1 is 945 bp, encoding a protein of 314 amino acids (aa), and the size of ORF2 is 705 bp, encoding a protein of 234 aa, which is 1 aa longer than that of the common PCV2 (233 aa). Korean PCV2b mutant strains had higher levels of nucleotide sequence identity to other PCV2b mutant strains (99.7–99.8 %) than to reference PCV2a (94.5–95.0 %) and PCV2b (95.5–96.1 %) strains. There was no difference in antigenic reactivity among PCV2a, PCV2b and PCV2b mutant strains to the polyclonal and monoclonal PCV2a antibodies. PCV2b mutant strains have distinct genetic characteristics but similar antigenic reactivity when compared to common PCV2a and 2b strains.