Orf Virus in Goats and Sheep: Veterinary Reference

Introduction

Orf virus (ORFV) is the prototypical member of the genus Parapoxvirus within the family Poxviridae and is the etiological agent of contagious ecthyma (CE), also known as contagious pustular dermatitis, in small ruminants [1, 2, 3]. The disease is characterized by proliferative, pustular, and scabby lesions on the lips, nostrils, oral mucosa, udder, and coronary band of goats and sheep [4, 5, 6]. ORFV is epitheliotropic and causes localized cutaneous infections that typically resolve within four to six weeks, although severe and persistent cases occur, particularly in young or immunocompromised animals [5, 3]. The virus possesses a double-stranded DNA genome of approximately 130 to 140 kilobase pairs (kbp) with terminal inverted repeats and a high GC content (approximately 64%) [7, 73, 74]. This article provides an exhaustive veterinary reference on ORFV in goats and sheep, integrating recent genomic, immunological, and diagnostic advances.

Virology and Genomic Organization

ORFV shares the typical poxvirus morphology: ovoid virions measuring 260 by 160 nm with a criss‑cross tubular surface pattern [8, 9]. The genome encodes approximately 130 open reading frames (ORFs), with a central conserved core region flanked by variable termini that contain genes involved in host range, virulence, and immune modulation [7, 73, 77]. Key structural proteins include the major envelope protein B2L (a homolog of vaccinia virus F13L) and the F1L protein, both of which are used as diagnostic antigens [10, 8, 11]. The A32L ATPase protein is another conserved target for molecular detection [10]. The scaffolding protein ORFV075 has been resolved by cryo‑electron microscopy, revealing a structure that facilitates virion assembly [12]. Whole‑genome analyses of isolates from Europe, South America, Africa, and Asia demonstrate substantial genetic diversity driven by recombination and positive selection [1, 7, 13, 14, 77].

Global Epidemiology and Host Range

ORFV circulates endemically in sheep and goat populations worldwide, with seroprevalence exceeding 80% in some regions [15, 16, 81]. The virus infects both domestic and wild Caprinae, including Iberian ibex (Capra pyrenaica) [17]. Outbreaks are frequently reported in Africa, the Middle East, Asia, and South America [18, 19, 20, 64, 71]. In Nigeria, concurrent infection of goats with ORFV and bovine herpesvirus 1 has been documented, highlighting the potential for viral co‑infections [72]. Transmission occurs through direct contact with infected animals or contaminated fomites; the virus is exceptionally stable in the environment, retaining infectivity for at least 35 years under refrigeration [21]. Mechanical vectors such as the common house fly (Musca domestica) can carry ORFV DNA, although their role in transmission is not fully quantified [79].

Pathogenesis and Clinical Manifestations

ORFV infection begins with viral entry into keratinocytes via host factors including KCNE4, a potassium channel subunit that mediates viral attachment and entry [22]. The virus replicates in the epidermis, inducing pronounced hyperplasia and angiogenesis, leading to the formation of papillomatous lesions that progress through papular, vesicular, pustular, and scab stages [4, 5]. Histologically, lesions show acanthosis, ballooning degeneration of keratinocytes, and intracytoplasmic eosinophilic inclusion bodies [23, 64]. A recent study using multi‑omics approaches in primary ovine fetal turbinate cells revealed that ORFV reprograms host metabolism, particularly amino acid and lipid pathways, to support viral replication [24].

Clinical signs in goats and sheep include proliferative scabs and crusts on the lips and muzzle, often extending to the nostrils, eyelids, and udder [4, 5]. In severe cases, lesions become hemorrhagic and prone to secondary bacterial infections, which can lead to mastitis, pneumonia, or septicemia [25, 5]. A study from Tanzania molecularly confirmed ORFV in goats with typical clinical signs across four districts [18]. In Lao goats, proliferative lip and facial lesions were causally linked to ORFV infection [15]. Vertical transmission of ORFV has been demonstrated in goats, with virus detected in fetal tissues and placenta, suggesting transplacental infection, and a prevention strategy using vaccination of pregnant does has been proposed [26]. Vertical transmission was also confirmed in a mouse model, further supporting the possibility of congenital infection [27].

Immune Evasion and Host Interactions

ORFV employs a multifaceted strategy to subvert host immune responses. The virus encodes a phosphatase, OH1, which interacts with and dephosphorylates signal transducer and activator of transcription 1 (STAT1), thereby inhibiting interferon‑γ signaling [28]. The ORFV129 protein binds to host complement C1q binding protein, reducing complement‑mediated neutralization [29]. Additionally, ORFV induces complete autophagy in infected cells by inhibiting the AKT/mTOR pathway and activating the ERK1/2/mTOR signaling cascade, a process that promotes viral replication [60]. Antibody‑dependent enhancement (ADE) of ORFV uptake has been observed; sub‑neutralizing antibodies can facilitate viral entry into Fc receptor‑bearing cells, potentially exacerbating infection [30]. The virus also downregulates innate immune sensing via suppression of pattern recognition receptor pathways [31].

Diagnostics

Accurate and rapid diagnosis of ORFV is essential for outbreak management and differentiation from other vesicular diseases such as foot‑and‑mouth disease, bluetongue, and sheeppox [15, 32, 33]. A combination of clinical examination, histopathology, molecular assays, and serology is recommended.

Molecular Detection

Real‑time polymerase chain reaction (qPCR) targeting the B2L gene is widely used [34, 32, 78]. A duplex TaqMan qPCR assay enabling simultaneous detection of ORFV and Brucella spp. in goats has been developed, facilitating co‑infection screening [34]. A freeze‑dried real‑time PCR assay for 11 sheep and goat pathogens, including ORFV, offers multiplexed detection with high throughput [32]. Isothermal amplification methods such as loop‑mediated isothermal amplification (LAMP) and recombinase‑aided amplification (RAA) provide rapid, field‑deployable alternatives [61, 63]. A visual closed‑tube LAMP assay for ORFV detection in sheep and goats has been validated [63]. Conventional PCR and sequencing of the B2L or A32L genes remain standard for phylogenetic characterization [10, 35, 36, 75].

Serological Assays

Indirect enzyme‑linked immunosorbent assays (ELISAs) based on recombinant ORFV114, B2L, or F1L antigens have been developed for serodiagnosis in goats [37, 11]. These assays exhibit high sensitivity and specificity and are suitable for serosurveillance [37].

Differential Diagnosis

ORFV infection must be differentiated from other causes of proliferative or vesicular lesions in small ruminants. The following table summarizes key differential diagnoses:

Diagnostic Workflow

The following decision tree outlines a recommended diagnostic approach:

flowchart TD
    A[Clinical suspicion of Orf], > B{Lesion type}
    B, >|Proliferative scabs| C[Collect swab/scab in viral transport medium]
    B, >|Vesicular/exudative| D[Collect vesicular fluid + swab]
    C, > E[DNA extraction]
    D, > E
    E, > F[Real-time PCR targeting B2L gene]
    F, > G{Result}
    G, >|Positive| H[Confirm ORFV infection]
    G, >|Negative| I[Perform differential PCR panel for FMDV, BTV, capripox]
    I, > J{Result}
    J, >|Other pathogen identified| K[Diagnose accordingly]
    J, >|No pathogen| L[Consider serology / histopathology]
    H, > M[Report to veterinary authority]
    K, > M

Transmission and Environmental Persistence

ORFV is shed in high titers from scab material and exudates [4, 78]. The virus has been detected in the saliva and milk of dairy goats, indicating potential for lactogenic and direct contact transmission [78]. Mechanical vectors such as house flies can transport ORFV DNA to skin abrasions [79]. Environmental stability is remarkable; ORFV remained infectious after 35 years of refrigeration [21]. This persistence complicates eradication and leads to recurrent outbreaks on farms.

Control and Vaccination

Control measures include strict biosecurity, isolation of infected animals, disinfection of contaminated facilities, and vaccination [2, 80]. Live attenuated vaccines are available but carry limited cross‑protection against heterologous strains [2, 33]. Recent vaccine development efforts have focused on rationally attenuated strains. Deletion of virulence genes such as OV132, OV112, and ORFV129 yields attenuated mutants that retain immunogenicity in goats [66, 69]. A quadruple gene‑deleted ORFV strain has been constructed as a vaccine candidate [38]. A triple‑gene deletion mutant showed safety and efficacy in target species [39]. A DNA prime‑protein boost strategy induced superior immune responses compared to adenovirus‑based vaccination in mice and sheep [59]. Vaccination of pregnant goats reduced vertical transmission of ORFV, supporting its use in endemic flocks [26]. However, challenges remain due to the virus’s ability to reinfect previously exposed animals because of its immune evasion mechanisms [31, 80].

Conclusion

Orf virus is a globally important pathogen of goats and sheep, causing substantial economic losses through morbidity, secondary infections, and trade restrictions. Recent advances in genomics, immune evasion biology, and molecular diagnostics have improved our understanding of ORFV epidemiology and pathogenesis. The development of next‑generation vaccines and field‑deployable diagnostic tools will enhance control strategies. Continued research into host‑pathogen interactions, particularly the mechanisms of vertical transmission and antibody‑dependent enhancement, is essential for designing effective interventions.

References

[1] Lostia G, Locci C, Rocchigiani AM et al. Unravelling the Evolutionary Complexity of Orf Virus: A Global and Multi-Host Perspective. Viruses. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41754565/

[2] Reichen C, Beirão BCB, Monteiro ALG. Contagious ecthyma in small ruminants: from etiology to vaccine challenges - a review. Vet Res Commun. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/39992468/

[3] Abu Ghazaleh R, Al-Sawalhe M, Abu Odeh I et al. Host range, severity and trans boundary transmission of Orf virus (ORFV). Infect Genet Evol. 2023. URL: https://pubmed.ncbi.nlm.nih.gov/37217030/

[4] Seung BJ, Khatiwada S, Rock DL et al. Temporal and spatial characterization of keratinocytes supporting orf virus replication. Front Cell Infect Microbiol. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39958991/

[5] Pintus D, Cancedda MG, Puggioni G et al. ORF virus causes tumor-promoting inflammation in sheep and goats. Vet Pathol. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38613413/

[6] Ewies SS, Tamam SM, Abdel-Moneim AS et al. Contagious ecthyma in Egypt: Clinical, virological and molecular explorations. Virology. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/37977083/

[7] Cacciabue M, Lozano Calderón LC, Moleres J et al. The whole genome analysis of four Orf virus strains from Europe and South America. Virus Evol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41727713/

[8] Golmei P, Venkatesan G, Kushwaha A et al. Expression of F1L, a vaccinia virus H3L transmembrane protein analogue of orf virus, and its successful purification as a diagnostic antigen. Virus Genes. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39136814/

[9] Efridi W, Jain H, Sathe NC et al. Orf Viral Infection. PubMed. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/32965862/

[10] Watjiranon W, Vannakovida C, Te-Chaniyom T et al. Molecular characterization and phylogenetic analysis of major envelope protein gene (B2L) and ATPase protein gene (A32L) of orf virus isolates from goats in Southern, Thailand. PLoS One. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41615951/

[11] Zheng W, Zhang Y, Gu Q et al. Development of an indirect ELISA against Orf virus using two recombinant antigens, partial B2L and F1L. J Virol Methods. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38336349/

[12] Kim S, Ko S, Kim M et al. Cryo-EM structure of orf virus scaffolding protein orfv075. Biochem Biophys Res Commun. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38968773/

[13] Coradduzza E, Scarpa F, Rocchigiani AM et al. The Global Evolutionary History of Orf Virus in Sheep and Goats Revealed by Whole Genomes Data. Viruses. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38275968/

[14] Du G, Wu J, Zhang C et al. The whole genomic analysis of the Orf virus strains ORFV-SC and ORFV-SC1 from the Sichuan province and their weak pathological response in rabbits. Funct Integr Genomics. 2023. URL: https://

[15] Jayasekara PP, Jenkins C, Kirkland PD et al. Causation and epidemiological features of proliferative lip and facial lesions in Lao goats. Trop Anim Health Prod. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/41144083/

[16] Durmuş E, Erdem-Şahinkesen E, Oğuzoğlu TÇ. Molecular perspective of Orf virus infection in Türkiye: a retrospective study between 2003 and 2021. Trop Anim Health Prod. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40721877/

[17] Estruch J, Serrano E, Martínez R et al. Outbreak of Contagious Ecthyma in Free-Ranging Iberian Ibex (Capra pyrenaica) in the Montgrí Massif Natural Park, Catalonia, Northeastern Spain. J Wildl Dis. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39021057/

[18] Mayenga C, Mwanandota JJ, Marisa J et al. Molecular Detection and Characterization of Orf Virus in Goats With Clinical Signs From Four Districts of Tanzania. Vet Med Sci. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41653104/

[19] Elkarhat Z, Tifrouin I, Bamouh Z et al. First identification of ORF virus causing contagious ecthyma in Morocco (MOR20): Genomic, phylogenetic, and sequence variants analyses for vaccine design. PLoS One. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40354355/

[20] Onoja BA, Adamu AM, Anyang AS et al. Detection and genetic characterization of orf virus from sheep and goats in Nigeria. Trop Anim Health Prod. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38351341/

[21] Duarte PM, Ferreira MNS, Cordeiro AM et al. Infectivity of Parapoxvirus Orf after 35 Years of Refrigeration. Curr Microbiol. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/41369791/

[22] Sun J, Ding Y, Zhou Q et al. KCNE4 is a crucial host factor for Orf virus infection by mediating viral entry. Virol J. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39118175/

[23] Dincer EN, Ozmen O. Immunohistochemical Evaluation of TLR-4, HSP-70 and Caspase-3 Expressions in Lesional Areas of Ecthyma Disease. Vet Dermatol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42068153/

[24] Zhang R, Gao F, Guan J et al. Multi-Omics Analyses Reveal Metabolic Alterations Regulated by Orf Virus in Primary Ovine Fetal Turbinate Cells. Viruses. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41754529/

[25] Price A, Marren C, Mulligan S et al. A Rare Case of Orf Virus Precipitating Methicillin-Resistant Staphylococcus Aureus Bacteremia Superinfection Leading to Native Hip Joint Septic Arthritis. J Orthop Case Rep. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40520743/

[26] Pang M, Munir F, Yao J et al. Vertical transmission of Orf virus in goats and its prevention. Vet Res. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41742266/

[27] Wen Y, Shakoor A, Munir F et al. Transplacental (vertical) transmission of Orf virus in mice (Mus musculus). Res Vet Sci. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42214274/

[28] Porley D, Olivero-Deibe N, Astrada V et al. Molecular insights of immune evasion by Orf Virus: the interaction and functional impact of viral OH1 phosphatase on STAT1. Biochimie. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41643804/

[29] Dan Y, Yang L, Zhang H et al. The orf virus 129 protein can inhibit immune responses by interacting with host complement C1q binding protein in goat turbinate bone cells. Vet Microbiol. 2023. URL: https://pubmed.ncbi.nlm.nih.gov/37270925/

[30] Tang X, Zhang C, Geng Q et al. Antibody-dependent enhancement of ORFV uptake into host cells. Virulence. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/39954287/

[31] AlDaif BA, Fleming SB. Innate Immune Sensing of Parapoxvirus Orf Virus and Viral Immune Evasion. Viruses. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40285029/

[32] Ke L, Hou G, Cao P et al. Establishment and validation of a real-time fluorescent PCR freeze-dried type assay for 11 sheep and goats pathogens. Vet J. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39424126/

[33] Bamouh Z, Tifrouin I, Elkarhat Z et al. Pathogenicity and phylogenetic analysis of ovine contagious ecthyma virus isolated during a sheeppox outbreak in Morocco. Microb Pathog. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39423917/

[34] Hu J, Zhou W, Liang S et al. A novel duplex TaqMan qPCR assay for rapid differential diagnosis and co-infection screening of Orf virus and Brucella spp. in goats. Vet Res Commun. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/42223521/

[35] Yıldırım Y, Bilge Dağalp S, Bozkurt G et al. Molecular Detection and Phylogenetic Analysis of Orf Virus From Dermatological Lesions in the Teats of Goats. Vet Med Sci. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/39792125/

[36] Zhang Z, Zhang X, Meng P et al. Molecular detection and phylogenetic analysis of Orf viruses from goats in Jiangxi province, China. Front Vet Sci. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38903681/

[37] Liang S, Hu J, Zhou W et al. Development and application of a novel indirect ELISA based on recombinant ORFV114 protein for serodiagnosis of Orf virus in goats. Vet Res Commun. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40996615/

[38] Zhang J, Xin R, Zhao J et al. Construction and Biological Characteristics of a Quadruple Gene-Deleted Strain of Orf Virus as a Vaccine Candidate. Viruses. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40573351/

[39] Shen Z, Liu B, Zhu Z et al. Construction of a Triple-Gene Deletion Mutant of Orf Virus and Evaluation of Its Safety, Immunogenicity and Protective Efficacy. Vaccines (Basel). 2023. URL: https://pubmed.ncbi.nlm.nih.gov/37243014/

[40] Kiszluk A, Woodfin MW, Gardner JM. Wrong Place at the Right Height: Scalp Orf in a Toddler With Dense Dermal Neutrophilic Infiltrate Mimicking Sweet Syndrome. J Cutan Pathol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41795885/

[41] Gündüz E, Tanriverdi ES, Alan S. [Orf Infection Localized in the Earlobe: The First Case Report in the Literature]. Mikrobiyol Bul. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41609451/

[42] Lu M, Liang Y, Zhou H et al. A rare case of human infection with Orf virus in China, 2024. Front Cell Infect Microbiol. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/41574294/

[43] Liu T, Song Z, Zhang L et al. Clinicopathological Features of Orf Virus Infection in the Human: A Rare Case Report of Extensive Skin Infections and Meta-Analysis. J Med Virol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41499533/

[44] Bao F, Li Z, Yang B et al. Dermatology images: Orf. J Am Acad Dermatol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41456799/

[45] Lv L, Gao F, Guan J et al. The identification and genetic characteristics of the Orf virus strain (ORFV-CL24) isolated from Jilin province, China. Front Microbiol. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/41070118/

[46] Danner MT, Schrodt CA, Tuttle A et al. Three Cases of Adolescent Orf Virus Skin and Soft Tissue Infection in Southeast Texas. Pediatr Infect Dis J. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40359245/

[47] Matre CB, Sakhare MP, Siddiqui MFMF et al. Molecular detection and occurrence of contagious ecthyma in goat. Trop Anim Health Prod. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/39891800/

[48] Teigen LC, Teigen JC, Li H et al. Orf Infection (Ecthyma Contagiosum) Transmitted from Sheep to Child: A Case Report. S D Med. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39821255/

[49] Xie J, Kou M, Wang Y et al. Retrospective research: identifying and conducting phylogenetic analyses on four Orf virus strains isolated in Yunnan province between 2021 and 2023-revealing their significance and characteristic features. Front Vet Sci. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39691377/

[50] Kälber KA, Enk A, Michel J et al. [Orf virus infection in a 53-year-old woman]. Dermatologie (Heidelb). 2025. URL: https://pubmed.ncbi.nlm.nih.gov/39230727/

[51] Mungmunpuntipantip R, Wiwanitkit V. Orf, a Human Parapoxvirus Infection. Adv Exp Med Biol. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38801578/

[52] Gómez Á, Lacasta D, Teresa Tejedor M et al. Use of a local anaesthetic and antiseptic wound formulation for the treatment of lambs naturally infected with Orf virus. Vet Microbiol. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38479302/

[53] Lv P, Fang Z, Guan J et al. Genistein is effective in inhibiting Orf virus infection in vitro by targeting viral RNA polymerase subunit RPO30 protein. Front Microbiol. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38389526/

[54] Salvi M, Tiecco G, Rossi L et al. Finger nodules with a papulovesicular hands and feet eruption: a complicated human Orf virus infection. BMC Infect Dis. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38229010/

[55] Sleiay M, Alqreea M, Alabdullah H et al. A 4-month-old male baby with an orf lesion on his nose: a rare case report. Ann Med Surg (Lond). 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38222745/

[56] Lacasta D, Ríos M, Ruiz de Arcaute M et al. Use of a Local Anaesthetic/Antiseptic Formulation for the Treatment of Lambs Experimentally Infected with Orf Virus. Animals (Basel). 2023. URL: https://pubmed.ncbi.nlm.nih.gov/37760362/

[57] Li S, Jing T, Zhu F et al. Genetic Analysis of Orf Virus (ORFV) Strains Isolated from Goats in China: Insights into Epidemiological Characteristics and Evolutionary Patterns. Virus Res. 2023. URL: https://pubmed.ncbi.nlm.nih.gov/37402415/

[58] Rossi L, Tiecco G, Venturini M et al. Human Orf with Immune-Mediated Reactions: A Systematic Review. Microorganisms. 2023. URL: https://pubmed.ncbi.nlm.nih.gov/37317112/