Bovine papillomaviruses (BPV) are a paraphyletic group of DNA viruses of the subfamily Firstpapillomavirinae of Papillomaviridae that are common in cattle. All BPVs have a circular double-stranded DNA genome. Infection causes warts (papillomas and fibropapillomas) of the skin and alimentary tract, and more rarely cancers of the alimentary tract and urinary bladder. They are also thought to cause the skin tumour equine sarcoid in horses and donkeys.
BPVs have been used as a model for studying papillomavirus molecular biology and for dissecting the mechanisms by which this group of viruses cause cancer.
Structure and genetic organisation
Like other papillomaviruses, BPVs are small non-enveloped viruses with an icosahedral capsid around 50–60 nm in diameter. The capsid is formed of the L1 and L2 structural proteins, with the L1 C-terminus exposed.
All BPVs have a circular double-stranded DNA genome of 7.3–8.0 kb. The genetic organisation of those BPVs which have been sequenced is broadly similar to other papillomaviruses. The open reading frames (ORFs) are all located on one strand, and are divided into early and late regions. The early region encodes nonstructural proteins E1 to E7. There are three viral oncoproteins, E5, E6 and E7; BPVs of the Xipapillomavirus group lack E6. The late region encodes structural proteins L1 and L2. There is also a non-coding long control region (LCR).
Types
Six types of BPV have been characterised, BPV-1 to BPV-6, which are divided into three broad subgroups. Deltapapillomavirus or fibropapillomaviruses (formerly known as subgroup A), including types 1 and 2, have a genome of around 7.9 kb. Similar papillomaviruses of ungulates (e.g. deer papillomavirus, European elk papillomavirus, ovine papillomavirus 1,2) are also found in this group. Like all members of the papillomavirus class, these viruses infect only keratinocytes (epithelial cells); however, unlike other papillomaviruses, they cause proliferation of both keratinocytes and fibroblasts, causing benign fibropapillomas involving both the epithelium and the underlying dermis. The specificity of the types differs: BPV-1 infects paragenital areas, including penis, teats and udders BPV-2 infects skin, alimentary canal and urinary bladder Xipapillomavirus or epitheliotropic BPVs (formerly known as subgroup B), including types 3, 4 and 6, have a smaller genome of around 7.3 kb and are unique among papillomaviruses in lacking the E6 oncoprotein. They infect keratinocytes (epithelial cells), causing pure papillomas involving only the epithelium. The specificity of the types differs: BPV-3 infects skin BPV-4 infects the upper alimentary tract BPV-6 infects teats and udders Epsilonpapillomavirus has the single member BPV-5, with features intermediate between the other two groups. BPV-5 infects teats and udders, and can cause both pure papillomas and fibropapillomas.
A further thirteen putative BPVs have recently been identified; the novel viruses have yet to be assigned to subgroups.
Pathology
BPV is highly prevalent, with around 50% of cattle being estimated to bear lesions in the UK. Cutaneous warts are most common in younger animals (under 2 years) and usually spontaneously regress due to the animal's immune response without significant scarring. The duration of infection is very variable (from one month to over a year) and recurrence is possible.
Warts caused by the Xipapillomavirus group have a cauliflower-like appearance and can attain the size of a fist; most common on the head, neck and shoulders, they may also occur in other locations. Cutaneous fibropapillomas caused by Deltapapillomavirus group have a nodular appearance. Although unsightly, most skin warts rarely cause problems except in show animals. However, large warts may bleed, potentially leading to secondary infections, and florid warts of the teat can cause mastitis and interfere with suckling and milking. Fibropapillomas can be troublesome when present in the genital area, causing pain and sometimes loss of reproductive functions as well as interfering with calving. Chronically immunosuppressed animals may develop extensive papillomatosis in the upper gastrointestinal tract, which can cause difficulties with eating and breathing.
Warts contain large amounts of infectious virus which is relatively stable. Transmission between animals is common via, for example, fence posts or halters. Warts on the teats of lactating cows are readily transmitted to calves via abrasions. Contaminated tattooing or tagging equipment is another common source of infection.