Analyze Diet
Scientific reports2025; 15(1); 29414; doi: 10.1038/s41598-025-15353-6

Accurate identification of bovine deltapapillomavirus in equine sarcoids by ddPCR.

Abstract: Sarcoids are benign and locally aggressive skin lesions that commonly affect horses and other equid species. Sarcoids are generally considered to be caused by bovine delta-papillomaviruses (δPVs) types 1 and 2 (BPV1 and BPV2, respectively). Moreover, while bovine δPV types 13 and 14 (BPV13 and BPV14, respectively) are also suspected to induce sarcoids, information regarding this possibility and the occurrence of multiple bovine δPV infections in sarcoids is scarce. This study aimed, for the first time, to assess BPV1, BPV2, BPV13, and BPV14 infections and co-infections in equine sarcoid samples of Austrian provenance, and to determine the intralesional DNA loads of the detected bovine δPV types using highly sensitive droplet digital polymerase chain reaction (ddPCR). BPV DNA was detected in 93 sarcoid samples. The analyses revealed that BPV1 was the predominant bovine δPV type in sarcoids from Austria, with 83/93 lesions testing BPV1-positive. Importantly, 66 tumors also contained BPV2 DNA. In six cases, a triple infection including BPV13 or BPV14 was noted, and one lesion showed a quadruple infection. This is the first ddPCR-based study to show multiple infections by all four bovine δPVs in equine sarcoids. Clinical data suggest that BPV1/2 co-infection may be associated with more severe and therapy-resistant disease. In-depth studies are required to investigate this possibility in greater detail.
Publication Date: 2025-08-11 PubMed ID: 40790360PubMed Central: PMC12340048DOI: 10.1038/s41598-025-15353-6Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study investigates the presence and quantity of four bovine deltapapillomavirus (δPV) types (BPV1, BPV2, BPV13, and BPV14) in equine sarcoids, which are common skin tumors in horses.
  • Using a sensitive detection method called droplet digital PCR (ddPCR), the research identifies single and multiple infections and explores their potential clinical significance.

Background

  • Sarcoids are benign but locally aggressive skin tumors frequently found in horses and related species.
  • These tumors are typically linked to infections by bovine deltapapillomaviruses, particularly BPV1 and BPV2.
  • BPV13 and BPV14 have also been implicated as possible causative agents, though evidence is limited.
  • Understanding the types of viral infections and co-infections in sarcoids can help clarify the disease mechanisms and improve treatment strategies.

Objective

  • To provide the first comprehensive assessment of BPV1, BPV2, BPV13, and BPV14 infections in Austrian equine sarcoid samples.
  • To quantify intralesional viral DNA loads using droplet digital PCR (ddPCR), a method enabling precise and highly sensitive detection of viral DNA.
  • To evaluate whether co-infections with multiple bovine δPVs occur and if such co-infections correlate with disease severity or treatment resistance.

Methods

  • Sample collection: 93 sarcoid tissue samples were collected from horses in Austria.
  • Detection technique: Droplet digital PCR (ddPCR) was employed to identify and quantify the DNA of BPV1, BPV2, BPV13, and BPV14 within the lesions.
  • Data analysis focused on identifying single vs. multiple δPV infections and measuring viral load per sample.

Key Findings

  • High prevalence of BPV DNA was observed in the sarcoid samples, confirming the viral association with these tumors.
  • BPV1 was the most common virus detected, present in 83 out of 93 lesions.
  • BPV2 DNA was also frequently identified, found in 66 of these BPV1-positive tumors, indicating frequent co-infections.
  • In six cases, triple infections including either BPV13 or BPV14 were detected, and one lesion showed the presence of all four types (quadruple infection).
  • This study is the first to use ddPCR to demonstrate simultaneous infections by all four bovine δPVs in equine sarcoids.
  • Preliminary clinical observations suggest that co-infections with BPV1 and BPV2 may be linked to more severe and therapy-resistant sarcoids.

Implications

  • The presence of multiple δPV infections could influence the biological behavior of sarcoids and affect treatment outcomes.
  • The use of ddPCR establishes a more sensitive and quantitative approach to detect and study papillomavirus infections in veterinary dermatology.
  • These findings highlight the need for further research to understand how viral co-infections contribute to tumor pathogenesis and resistance to therapy.

Conclusion

  • The research expands the knowledge of viral involvement in equine sarcoids by confirming frequent multiple δPV infections with BPV1, BPV2, BPV13, and BPV14.
  • Enhanced diagnostic techniques like ddPCR can improve detection accuracy and help in assessing the clinical impact of these infections.
  • Future studies are necessary to determine the exact role of these multiple viral infections in disease progression and treatment resistance in horses.

Cite This Article

APA
Cutarelli A, Buonavoglia A, Fusco G, Pellicanò R, Napoletano M, Brandt S, Roperto S. (2025). Accurate identification of bovine deltapapillomavirus in equine sarcoids by ddPCR. Sci Rep, 15(1), 29414. https://doi.org/10.1038/s41598-025-15353-6

Publication

ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 15
Issue: 1
Pages: 29414
PII: 29414

Researcher Affiliations

Cutarelli, Anna
  • Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Naples, Italy.
Buonavoglia, Alessio
  • Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
Fusco, Giovanna
  • Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Naples, Italy.
Pellicanò, Roberta
  • Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Naples, Italy.
Napoletano, Michele
  • Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Naples, Italy.
Brandt, Sabine
  • Research Group Oncology, Department for Companion Animals and Horses, Veterinary University, Vienna, Austria.
Roperto, Sante
  • Dipartimento di Medicina Veterinaria e delle Produzioni Animali, Università degli Studi di Napoli Federico II, Naples, Italy. sante.roperto@unina.it.

MeSH Terms

  • Animals
  • Horses
  • Cattle
  • Horse Diseases / virology
  • Horse Diseases / diagnosis
  • Papillomavirus Infections / veterinary
  • Papillomavirus Infections / virology
  • Papillomavirus Infections / diagnosis
  • Polymerase Chain Reaction / methods
  • DNA, Viral / genetics
  • Skin Neoplasms / virology
  • Skin Neoplasms / veterinary
  • Deltapapillomavirus / genetics
  • Deltapapillomavirus / isolation & purification
  • Bovine papillomavirus 1 / genetics
  • Bovine papillomavirus 1 / isolation & purification
  • Austria
  • Coinfection / virology
  • Coinfection / veterinary

Conflict of Interest Statement

Declarations. Competing interests: The authors declare no competing interests. Ethics declaration: The animal collection and handling and tissue sampling procedures were performed in accordance with the ethics guidelines of the Veterinary University Vienna and Austrian Law. Animal studies performed in Naples were approved by the Institutional Animal Care and Use Committee (Protocol PG/2024/0023599, Naples University Federico II). Permission to collect samples was obtained from the animals’ owners who were previously informed and in agreement with the purpose and methods used.

References

This article includes 51 references
  1. Nasir L, Campo MS. Bovine papillomaviruses: their role in the aetiology of cutaneous tumour of Bovids and equids.. 243–254 (2008).
  2. Knottenbelt DC. The equine sarcoid -Why are there so many treatment options.. 243–262 (2019).
    doi: 10.1016/j.cveq.2019.03.006pubmed: 31097356google scholar: lookup
  3. Chambers G. Association of bovine papillomavirus with the equine sarcoid.. 1055–1062 (2003).
    doi: 10.1099/vir.0.18947-0pubmed: 12692268google scholar: lookup
  4. Lunardi M. Genetic characterization of a novel bovine papillomavirus member of the deltapapillomavirus genus.. 207–213 (2013).
    doi: 10.1016/j.vetmic.2012.08.030pubmed: 22999523google scholar: lookup
  5. Lunardi M. Bovine papillomavirus type 13 DNA in equine sarcoids.. 2167–2171 (2013).
    doi: 10.1128/jcm.00371-13pmc: PMC3697707pubmed: 23637294google scholar: lookup
  6. Roperto S, Munday JS, Corrado F, Goria M, Roperto F. Detection of bovine papillomavirus type 14 DNA sequences in urinary bladder tumors in cattle.. 1–4 (2016).
    doi: 10.1016/j.vetmic.2016.04.007pubmed: 27283849google scholar: lookup
  7. zur Hausen H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis.. 690–698 (2000).
    doi: 10.1093/jnci/92.9.690pubmed: 10793105google scholar: lookup
  8. Rector A, Van Ranst M. Animal papillomaviruses.. 213–223 (2013).
    doi: 10.1016/j.virol.2013.05.007pubmed: 23711385google scholar: lookup
  9. de Villiers EM, Fauquet C, Broker TR, Bernard HU, Zur Hausen H. Classification of papillomaviruses.. 17–27 (2004).
    doi: 10.1016/j.virol.2004.03.033pubmed: 15183049google scholar: lookup
  10. Carr EA, Theon AP, Madewell BR, Griffey SM, Hitchcock ME. Bovine papillomavirus DNA in neoplastic and nonneoplastic tissues obtained from horses with and without sarcoids in the Western united States.. 741–744 (2001).
    doi: 10.2460/ajvr.2001.62.741pubmed: 11341396google scholar: lookup
  11. Wobeser BK. Epidemiology of equine sarcoids in horses in Western Canada.. 1103–1108 (2010).
    pmc: PMC2942047pubmed: 21197201
  12. Hainisch EK. Bovine papillomavirus type 1 and 2 virion-infected primary fibroblasts constitute a near-natural equine sarcoid model.. 2658 (2022).
    doi: 10.3390/v14122658pmc: PMC9781842pubmed: 36560661google scholar: lookup
  13. Gysens L, Vanmechelen B, Haspeslagh M, Maes P, Martens A. New approach for genomic characterisation of equine sarcoid-derived BPV-1/-2 using nanopore-based sequencing.. 8 (2022).
    doi: 10.1186/s12985-021-01735-5pmc: PMC8740336pubmed: 34991633google scholar: lookup
  14. Roperto S. Bovine papillomavirus type 13 expression in the urothelial bladder tumours of cattle.. 628–634 (2016).
    doi: 10.1111/tbed.12322pubmed: 25597262google scholar: lookup
  15. Gasparotto G. Characterization of bovine papillomavirus types detected in cattle rumen tissues from Amazon region, Brazil.. 2262 (2024).
    doi: 10.3390/ani14152262pmc: PMC11311079pubmed: 39123787google scholar: lookup
  16. Jindra C, Kamjunke AK, Jones S, Brandt S. Screening for bovine papillomavirus type 13 (BPV13) in a European population of sarcoid-bearing equids.. 662–669 (2021).
    doi: 10.1111/evj.13501pmc: PMC9292424pubmed: 34459020google scholar: lookup
  17. Munday JS, Knight CG, Howe L. The same papillomavirus is present in feline sarcoids from North America and new Zealand but not in any non-sarcoid feline samples.. 97–100 (2010).
    doi: 10.1177/104063871002200119pubmed: 20093693google scholar: lookup
  18. Orbell GM, Young S, Munday JS. Cutaneous sarcoids in captive African lions associated with feline sarcoid-associated papillomavirus infection.. 1176–1179 (2011).
    doi: 10.1177/0300985810391111pubmed: 21169593google scholar: lookup
  19. Munday JS. Genomic characterisation of the feline sarcoid-associated papillomavirus and proposed classification as Bos Taurus papillomavirus type 14.. 289–295 (2015).
    doi: 10.1016/j.vetmic.2015.03.019pubmed: 25840470google scholar: lookup
  20. Munday JS, Knight CG. Amplification of feline sarcoid-associated papillomavirus DNA sequences from bovine skin.. 341–344 (2010).
  21. Kojabad AA. Droplet digital PCR of viral DNA/RNA, current progress, challenges, and future perspectives.. 4182–4197 (2021).
    doi: 10.1002/jmv.26846pmc: PMC8013307pubmed: 33538349google scholar: lookup
  22. Li H. Application of droplet digital PCR to detect the pathogens of infectious diseases.. BSR20181170 (2018).
    doi: 10.1042/BSR20181170pmc: PMC6240714pubmed: 30341241google scholar: lookup
  23. Biron VL. Detection of human papillomavirus type16 in oropharyngeal squamous cell carcinoma using droplet digital polymerase chain reaction.. 1544–1551 (2016).
    doi: 10.1002/cncr.29976pubmed: 26989832google scholar: lookup
  24. Isaac A. Ultrasensitive detection of oncogenic human papillomavirus in oropharyngeal tissue swabs.. 5 (2017).
    doi: 10.1186/s40463-016-0177-8pmc: PMC5237494pubmed: 28088212google scholar: lookup
  25. Lillsunde Larsson G, Helenius G. Digital droplet PCR (ddPCR) for the detection and quantification of HPV 16, 18, 33 and 45 – a short report.. 521–527 (2017).
    doi: 10.1007/s13402-017-0331-ypmc: PMC5608796pubmed: 28748500google scholar: lookup
  26. De Falco F, Corrado F, Cutarelli A, Leonardi L, Roperto S. Digital droplet for detection and quantification of Circulating bovine deltapapillomavirus.. 1345–1352 (2021).
    doi: 10.1111/tbed.13795pubmed: 33350088google scholar: lookup
  27. De Falco F. Molecular epidemiology of ovine papillomavirus infection in Southern Italy.. 7903922 (2021).
    doi: 10.3389/fvets.2021.790392pmc: PMC8645557pubmed: 34881323google scholar: lookup
  28. Cutarelli A. Prevalence and genotype distribution of caprine papillomavirus in peripheral blood of healthy goats in farms from three European countries.. 1213150 (2023).
    doi: 10.3389/fvets.2023.1213150pmc: PMC10310300pubmed: 37396991google scholar: lookup
  29. Brandt S. BPV-1 infection is not confined to the dermis but also involves the epidermis of equine sarcoids.. 35–40 (2011).
    doi: 10.1016/j.vetmic.2010.12.021pubmed: 21242040google scholar: lookup
  30. Hainisch EK, Brandt S. Equine Sarcoids.. Robinson’s Current Therapy in Equine Medicine Vol.1 Saunders Elsevier. St Louis, MO, USA (2015).
  31. De Falco F, Cutarelli A, Fedele ML, Catoi C, Roperto S. Molecular findings and virological assessment of bladder papillomavirus infection in cattle.. 1–7 (2024).
  32. Roperto S, Cutarelli A, Corrado F, De Falco F, Buonavoglia C. Detection and quantification of bovine papillomavirus DNA by digital droplet PCR in sheep blood.. 10292 (2021).
    doi: 10.1038/s41598-021-89782-4pmc: PMC8119674pubmed: 33986444google scholar: lookup
  33. Cutarelli A, De Falco F, Uleri V, Buonavoglia C, Roperto S. The diagnostic value of the droplet digital PCR for the detection of bovine deltapapillomavirus in goats by liquid biopsy.. 3624–3630 (2021).
    doi: 10.1111/tbed.13971pubmed: 33386672google scholar: lookup
  34. Cutarelli A. Ultrasensitive detection and quantification of bovine deltapapillomavirus in the semen of healthy horses.. 769 (2025).
    doi: 10.1038/s41598-024-81682-7pmc: PMC11700219pubmed: 39755719google scholar: lookup
  35. De Falco F, Cutarelli A, Pellicanò R, Brandt S, Roperto S. Molecular detection and quantification of ovine papillomavirus DNA in equine sarcoid.. 6453158 (2024).
    pmc: PMC12016688pubmed: 40303025doi: 10.1155/2024/6453158google scholar: lookup
  36. Cutarelli A. Molecular detection of transcriptionally active ovine papillomaviruses in commercial equine semen.. 1427370 (2024).
    doi: 10.3389/fvets.2024.1427370pmc: PMC11253197pubmed: 39021410google scholar: lookup
  37. Hindson BJ. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number.. 8604–8610 (2011).
    doi: 10.1021/ac202028gpmc: PMC3216358pubmed: 22035192google scholar: lookup
  38. Daudt C. How many papillomavirus species can go undetected in papilloma lesions.. 36480 (2017).
    doi: 10.1038/srep36480pmc: PMC5093584pubmed: 27808255google scholar: lookup
  39. Sauthier JT. The genetic diversity of papillomavirome in bovine teat papilloma lesions.. 51 (2021).
    doi: 10.1186/s42523-021-00114-3pmc: PMC8317299pubmed: 34321106google scholar: lookup
  40. dos Souza A. Characterization of papillomatous lesions and genetic diversity of bovine papillomavirus from the Amazon region.. 719 (2025).
    doi: 10.3390/v17050719pmc: PMC12115847pubmed: 40431730google scholar: lookup
  41. Chaturvedi AK. Human papillomavirus infection with multiple types: pattern of coinfection and risk of cervical disease.. 910–920 (2011).
    doi: 10.1093/infdis/jiq139pmc: PMC3068034pubmed: 21402543google scholar: lookup
  42. Akinjyi I. HPV infection patterns and viral load distribution: implication on cervical cancer prevention in Western Kenia.. 329–336 (2025).
  43. Guo W. Epidemiological study of human papillomavirus infection in 105,679 women in wuhan, China.. 1111 (2024).
    doi: 10.1186/s12879-024-10011-0pmc: PMC11457396pubmed: 39375610google scholar: lookup
  44. Herrero R. Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica.. 464–474 (2020).
    doi: 10.1093/jnci.92.6.464pubmed: 10716964google scholar: lookup
  45. Luo Q. Epidemiologic characteristics of high-risk HPV and the correlation between multiple infections and cervical lesions.. 667 (2023).
    doi: 10.1186/s12879-023-08634-wpmc: PMC10560423pubmed: 37805467google scholar: lookup
  46. Capparelli R. Mannose-binding lectin haplotypes influence Brucella abortus infection in the water Buffalo (Bubalus bubalis).. 157–165 (2008).
    doi: 10.1007/s00251-008-0284-4pubmed: 18330558google scholar: lookup
  47. De Falco F. Bovine delta papillomavirus E5 oncoprotein interacts with TRIM25 and hampers antiviral innate immune response mediated by RIG-I-like receptors.. 658762 (2021).
    doi: 10.3389/fimmu.2021.658762pmc: PMC8223750pubmed: 34177899google scholar: lookup
  48. De Falco F. Bovine delta papillomavirus E5 oncoprotein negatively regulates the cGAS-STING signaling pathway in cattle in a spontaneous model of viral disease.. 937736 (2022).
    doi: 10.3389/fimmu.2022.937736pmc: PMC9597257pubmed: 36311756google scholar: lookup
  49. Brandt S, Haralambus R, Schoster A, Kirnbauer R, Stanek C. Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines.. 1390–1395 (2008).
    doi: 10.1099/vir.0.83568-0pubmed: 18474554google scholar: lookup
  50. Brandt S. A subset of equine sarcoids harbours BPV-1 DNA in a complex with L1 major capsid protein.. 433–441 (2008).
    doi: 10.1016/j.virol.2008.02.014pubmed: 18395238google scholar: lookup
  51. De Falco F. Possible etiological association of ovine papillomaviruses with bladder tumors in cattle. 2023;199084.

Citations

This article has been cited 0 times.