Papillomaviruses in equids: A decade of discovery and more to come?

The case report that this clinical commentary accompanies (Vichi et al. 2022) describes the diagnosis and treatment of a 2-year-old horse with cutaneous papillomatosis lesions, attributed to Equus caballus papillomavirus 2 (EcPV2) infection, concurrent habronemiasis. additional pathology caused by presence Habronematidae larvae necessitated surgical removal lesions. Without coinfection, infection lesions could have progressed in several ways. number known papillomaviruses is increasing for many species, including equids, as range pathologies which they are implicated. This article summarises presentations papillomavirus-associated infections equids outlines underlying host-viral biology. Papillomavirus (PV) may be latent, subclinical or result lesion development. Active cause self-resolving benign proliferative more severe persistent disease, malignant cancers (Fig 1). To date, nine (EcPV1 9) two asinine (EaPV1 2) been identified (Papillomavirus Episteme). Additionally, bovine (BPV) types 1, (Chambers 2003) 13 (Lunardi 2013) infect horses donkeys equine sarcoids, an unusual example cross-species host-specific family viruses. In humans, 225 (HPVs) Episteme), at least 14 can cancer metastatic potential (high-risk HPVs (hrHPVs)) (World Health Organization 2020). An infectious human cervical was first suspected from 1950s onwards, hrHPVs 16 18 were characterised causes 1980s (Dürst 1983; Boshart 1984), discovery Harald zur Hausen awarded Nobel Prize (Nobel 2008). It now almost all cases cancer, well significant proportion other anogenital approximately 25% head neck (de Martel 2017). Moreover, implicated over 5% worldwide (Berman Schiller Given much lower numbers PVs so far discovered veterinary example, 23 dogs 27 cattle it seems there discover, both low high significance. already become newly pathological conditions. There has considerable increase equine-infecting last decade, prior only EcPV1 (Ghim 2004) BPV1 BPV2 fully characterised. previously involved genital papillomas carcinomas aural plaques, but EcPV2 EcPV3, respectively, not samples these until 2011 (Lange 2011). EcPVs 4 7 reported 2013 2013), EcPV8 2018 (Linder 2018) EcPV9 2019 (Li 2019). 2013, BPV13 linked sarcoids after being detected Brazil 2013). asinus 1 (EaPV1) 2014 Asinara white no appears pathogenicity (Lecis 2014), whereas severe, generalised 2018). Furthermore, recently associated squamous cell (SCCs), its DNA having subset SCCs stomach (Alloway 2020) (Sykora 2017) genitalia. Most strictly epitheliotrophic, infecting dermal keratinocytes epithelium. A also infects mesenchymal cells; BPV1, transform fibroblasts (Bocaneti 2016). life cycle epithelial differentiation, strategy enables virions shed during desquamation helps virus escape immune response 2). double stranded circular genome, encoding early (E) genes viral genome replication oncogenesis, late (L) encode capsid proteins 3). expressed deeper tissue layers superficially (Nasir Campo productive, infected hosts, classic papillomatosis. EcPV1-associated “warts” mostly occur on face distal limbs young horses. These typically spontaneously regress within few weeks, when host clears becomes reinfection (Dong Benign fibropapillomas induced follow same course, growths include proliferating keratinocytes. minority cases, if immunocompromised, cleared widespread (Turk 2005). As discussed report, co-infection pathogens influence survival pathogenesis. Some PV involve productive chronic (Knight Equine plaques thought EcPV4 EcPV6, co-infections EcPV5 appear common (Mira mentioned one skin pathogen aid invasion another. Although usually clinically significant, do finding PV-like structures electron microscopy (Fairley Haines 1992) suggests virion production. thousands coalescing hyperkeratotic papules particularly trunk, three persisted year three, euthanased others lost follow-up. Viral protein suggesting too increasingly some horse. SCC containing aged multiple (Peters-Kennedy EcPV8-containing extensive inguinal region Integration into dead end because nonproductive. However, important step hrHPV-induced oncogenesis seen most, although all, (Groves Coleman 2015). possible nonproductive maintained episomal form, occurs latency (De Leo BPV remain integrate, meaning expression alone able cells (Amtmann 1980). Equids traditionally considered hosts infective isolated (Hainisch reports evidence apparent equid-equid transmission sarcoid outbreaks (Ragland 1966; Reid 1994; Nasir 2008) equid-adapted variants 2007). unclear how produced fibroblasts, given production primarily tumours variable epidermal involvement (Martens 2000). found epidermis dermis L1 (Brandt 2011), half tested positive assay detects complexed 2008), BPV2. unusually 2022). area nasal oral cavities facial warts presumed contain EcPV2. normal precancerous (Bogaert 2012). higher than healthy animals, “oncogenic rather commensal virus” (summarised Sykora Brandt situ hybridisation study using probes material 80–100% neoplastic SCCs, vessels regional lymph nodes metastases, providing stronger causative PCR positivity (Zhu integrate do. qPCR (quantitative PCR) study, EcPV2-positive contained copies E6 oncogene regulatory E2 gene, disrupted integration 3), per anatomical distribution PV-induced diseases suggestive direct/fomite transmission. For face, (fibro)papillomas often udder. nonenveloped viruses, resistant freezing desiccation (Roden 1997), therefore persist environment time. Virions new via abrasions cannot invade intact thought, yet proven, transmitted flying insects, such black flies (Simulium spp.), horses' ears 2014). principle insects acting mechanical vectors experimentally proven rabbits (Dalmat 1958). insect vector, UK biting nonbiting (Finlay 2009). date. Transmission mechanisms sites unclear. causing head, genitalia humans sexually transmitted, numerous routes, horizontal vertical, proposed (Tumban 2019; Mchome 2021). blood semen equines (Silva smegma gastric larynx guttural pouch (Hibi 2019), mechanisms. Effective prophylactic vaccinations developed patients, post-exposure vaccination does effective. HPV vaccines virus-like particles (VLP) empty shells. Over 90% efficacy against demonstrated, offer cross-protection similar (Cutts VLP shown safe immunogenic 2012), protect experimental challenge PV-associated diseases, further research affecting horse, cause, warranted. market should explored. No conflicts interest declared. Not applicable commentary. None. Thanks Lubna Nasir, Collette Britton, William Weir, Dawn Dunbar Sarah Krumrie their suggestions regarding article.