| Bovine papillomaviruses | |
|---|---|
 | |
| Bovine papillomavirus (3D reconstruction) | |
Scientific classification | |
| (unranked): | Virus |
| Realm: | Monodnaviria |
| Kingdom: | Shotokuvirae |
| Phylum: | Cossaviricota |
| Class: | Papovaviricetes |
| Order: | Zurhausenvirales |
| Family: | Papillomaviridae |
| Subfamily: | Firstpapillomavirinae |
| Groups included | |
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Bovine papillomaviruses (BPV) are aparaphyletic group ofDNA viruses of the subfamilyFirstpapillomavirinae ofPapillomaviridae that are common incattle. All BPVs have acircular double-stranded DNA genome. Infection causeswarts (papillomas and fibropapillomas) of theskin andalimentary tract, and more rarely cancers of the alimentary tract andurinary bladder. They are also thought to cause the skin tumourequine sarcoid inhorses anddonkeys.
BPVs have been used as a model for studying papillomavirus molecular biology and for dissecting the mechanisms by which this group of viruses causecancer.
Like other papillomaviruses, BPVs are small non-enveloped viruses with anicosahedralcapsid around 50–60 nm in diameter.[2][3] The capsid is formed of the L1 and L2structural proteins, with the L1C-terminus exposed.[2][4]
All BPVs have acircular double-strandedDNA genome of 7.3–8.0 kb. The genetic organisation of those BPVs which have been sequenced is broadly similar to other papillomaviruses. Theopen 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 viraloncoproteins, E5, E6 and E7; BPVs of theXipapillomavirus group lack E6. The late region encodes structural proteins L1 and L2. There is also a non-coding long control region (LCR).[2]
Six types of BPV have been characterised, BPV-1 to BPV-6, which are divided into three broad subgroups.
A further thirteen putative BPVs have recently been identified; the novel viruses have yet to be assigned to subgroups.[5]
BPV is highly prevalent, with around 50% of cattle being estimated to bear lesions in the UK.[6] Cutaneous warts are most common in younger animals (under 2 years) and usually spontaneously regress due to the animal'simmune response without significant scarring. The duration of infection is very variable (from one month to over a year) and recurrence is possible.[7]
Warts caused by theXipapillomavirus 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.[7] Cutaneous fibropapillomas caused byDeltapapillomavirus group have a nodular appearance.[7] 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 causemastitis and interfere with suckling and milking.[3] Fibropapillomas can be troublesome when present in the genital area, causing pain and sometimes loss of reproductive functions as well as interfering with calving.[3][7] Chronically immunosuppressed animals may develop extensive papillomatosis in the upper gastrointestinal tract, which can cause difficulties with eating and breathing.[3]
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.[citation needed]
BPV-4 causessquamous cell carcinomas of the alimentary tract, and BPV-1/2 causes carcinomas andhaemangioendotheliomas of the urinary bladder, in both cases in animals that have fed onbracken (Pteridium aquilinum).[3] Such cancers are common in locations where grazing land is infested with bracken, such as the westernScottish Highlands, southernItaly and theNasampolai Valley inKenya.[3] Bracken contains severalimmunosuppressants andmutagens, includingquercetin andptaquiloside. Consumption of large quantities by cattle leads to anacute poisoning syndrome[8] with symptoms ofbone marrow depletion, while at lower levels of long-term consumption it acts as a cancercofactor.[3][9]Carcinogenesis is a multistep process; tumours also contain activatedRas, as well as mutation or downregulation of thetumour suppressor genesp53 in alimentary tract cancers andfragile histidine tetrads (FHIT) in urinary bladder cancers.[3] Viral particles are not produced in either alimentary tract or urinary bladder tumours.[3]
These bracken-associated tumours might form a model for some types of humanoesophageal cancer.Human papillomavirus DNA has been detected in around 18% of squamous cell carcinomas of the oesophagus,[10] and there is an association between exposure to or consumption of bracken (which is used as a foodstuff and herbal remedy inSouth America,China,Japan,Korea and other countries) and risk of developing oesophageal cancer.[3]
BPV-1 and BPV-2 can also inducesarcomas andfibrosarcomas in other mammals, including equids (equine sarcoid)[11] and, experimentally, rabbits, hamsters and mice[12][13] (and reviewed in).[2] Viral particles are not produced during infection of other species and, unlike in tumours associated withhuman papillomavirus, the viral DNA is not integrated into the host genome.[11]
Equine sarcoid, a naturally occurring skin tumour affecting horses, donkeys and mules, is associated with strains of BPV-1/2 which may be equine specific.[11] The lesions can occur anywhere on the body, often multiply, with the limbs, thorax–abdomen, head and paragenital areas being particularly commonly affected.[11][14] The method of transmission is currently unclear; the involvement offace flies (Musca autumnalis) has been suggested, and transmission via contaminated tack is likely.[11] The disease forms the only known example of natural cross-species infection by a papillomavirus. The involvement of BPV leads to hope that vaccination orantiviral therapy might be possible in the future for this common tumour.[citation needed]
Treatment is not usually required, as most warts eventually regress spontaneously. Surgical removal is possible but may lead to recurrence.[7] Disinfection withformaldehyde of stalls, fence posts and other environmental virus reservoirs can prevent transmission.[7]
Vaccines against BPV types 1, 2 and 4 have been developed byM. Saveria Campo and others.[3][6]
These vaccine systems have served as models for the successful development of prophylactic vaccines against thehuman papillomavirus types associated withcervical andanal cancers.[15] BothGardasil (a quadrivalent prophylacticHPV vaccine licensed in 2006) andCervarix (a bivalent prophylactic vaccine license in the EU in 2007 and USA in 2009) contain virus-like particles assembled from L1 protein, an approach successful against BPV, and both vaccines induce sustained immunity.[16][17] Various therapeutic HPV vaccines based on E6, E7 and L2 are currently in early-stage clinical trials.[18]