Bovine papillomavirus

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Bovine papillomaviruses
Papillomavirus capsid.png
Bovine papillomavirus (3D reconstruction)
Scientific classification Red Pencil Icon.png
(unranked): Virus
Realm: Monodnaviria
Kingdom: Shotokuvirae
Phylum: Cossaviricota
Class: Papovaviricetes
Order: Zurhausenvirales
Family: Papillomaviridae
Subfamily: Firstpapillomavirinae
Groups included

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.

Contents

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. [2] [3] The capsid is formed of the L1 and L2 structural proteins, with the L1 C-terminus exposed. [2] [4]

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). [2]

Types

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]

Pathology

Large warts, showing the cauliflower-like appearance Poreas aumea khouitir abdellah.jpg
Large warts, showing the cauliflower-like appearance

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's immune 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 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. [7] Cutaneous fibropapillomas caused by Deltapapillomavirus 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 cause mastitis 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]

Multiple small facial warts Bovine warts.jpg
Multiple small facial warts

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 ]

Association with cancer

Cattle

BPV-4 causes squamous cell carcinomas of the alimentary tract, and BPV-1/2 causes carcinomas and haemangioendotheliomas of the urinary bladder, in both cases in animals that have fed on bracken ( Pteridium aquilinum ). [3] Such cancers are common in locations where grazing land is infested with bracken, such as the western Scottish Highlands, southern Italy and the Nasampolai Valley in Kenya. [3] Bracken contains several immunosuppressants and mutagens, including quercetin and ptaquiloside. Consumption of large quantities by cattle leads to an acute poisoning syndrome [8] with symptoms of bone marrow depletion, while at lower levels of long-term consumption it acts as a cancer cofactor. [3] [9] Carcinogenesis is a multistep process; tumours also contain activated Ras, as well as mutation or downregulation of the tumour suppressor genes p53 in alimentary tract cancers and fragile histidine tetrads (FHIT) in urinary bladder cancers. [3] Viral particles are not produced in either alimentary tract or urinary bladder tumours. [3]

Cows feeding on bracken are at risk of developing BPV-associated cancers Cow Bickerton Aug 2007.jpg
Cows feeding on bracken are at risk of developing BPV-associated cancers

These bracken-associated tumours might form a model for some types of human oesophageal 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 in South America, China, Japan, Korea and other countries) and risk of developing oesophageal cancer. [3]

Other mammals

BPV-1 and BPV-2 can also induce sarcomas and fibrosarcomas 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 with human 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 of face 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 or antiviral therapy might be possible in the future for this common tumour.[ citation needed ]

Treatment, prophylaxis and prevention

Treatment is not usually required, as most warts eventually regress spontaneously. Surgical removal is possible but may lead to recurrence. [7] Disinfection with formaldehyde of stalls, fence posts and other environmental virus reservoirs can prevent transmission. [7]

Vaccination

Vaccines against BPV types 1, 2 and 4 have been developed by M. Saveria Campo and others. [3] [6]

These vaccine systems have served as models for the successful development of prophylactic vaccines against the human papillomavirus types associated with cervical and anal cancers. [15] Both Gardasil (a quadrivalent prophylactic HPV vaccine licensed in 2006) and Cervarix (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]

Related Research Articles

<span class="mw-page-title-main">Wart</span> Small, rough growth resembling a cauliflower or a solid blister

Warts are typically small, rough, hard growths that are similar in color to the rest of the skin. They typically do not result in other symptoms, except when on the bottom of the feet, where they may be painful. While they usually occur on the hands and feet, they can also affect other locations. One or many warts may appear. They are not cancerous.

<span class="mw-page-title-main">Human papillomavirus infection</span> Human disease

Human papillomavirus infection is caused by a DNA virus from the Papillomaviridae family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV and two strains – HPV16 and HPV18 – account for 70% of cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.

<span class="mw-page-title-main">Genital wart</span> Sexually transmitted infection caused by certain types of human papillomaviruses

Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They are generally pink in color and project out from the surface of the skin. Usually they cause few symptoms, but can occasionally be painful. Typically they appear one to eight months following exposure. Warts are the most easily recognized symptom of genital HPV infection.

<i>Papillomaviridae</i> Family of viruses

Papillomaviridae is a family of non-enveloped DNA viruses whose members are known as papillomaviruses. Several hundred species of papillomaviruses, traditionally referred to as "types", have been identified infecting all carefully inspected mammals, but also other vertebrates such as birds, snakes, turtles and fish. Infection by most papillomavirus types, depending on the type, is either asymptomatic or causes small benign tumors, known as papillomas or warts. Papillomas caused by some types, however, such as human papillomaviruses 16 and 18, carry a risk of becoming cancerous.

<span class="mw-page-title-main">Oncovirus</span> Viruses that can cause cancer

An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term "oncornaviruses" was used to denote their RNA virus origin. With the letters "RNA" removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.

<span class="mw-page-title-main">Laryngeal papillomatosis</span> Medical condition

Laryngeal papillomatosis, also known as recurrent respiratory papillomatosis (RRP) or glottal papillomatosis, is a rare medical condition in which benign tumors (papilloma) form along the aerodigestive tract. There are two variants based on the age of onset: juvenile and adult laryngeal papillomatosis. The tumors are caused by human papillomavirus (HPV) infection of the throat. The tumors may lead to narrowing of the airway, which may cause vocal changes or airway obstruction. Laryngeal papillomatosis is initially diagnosed through indirect laryngoscopy upon observation of growths on the larynx and can be confirmed through a biopsy. Treatment for laryngeal papillomatosis aims to remove the papillomas and limit their recurrence. Due to the recurrent nature of the virus, repeated treatments usually are needed. Laryngeal papillomatosis is primarily treated surgically, though supplemental nonsurgical and/or medical treatments may be considered in some cases. The evolution of laryngeal papillomatosis is highly variable. Though total recovery may be observed, it is often persistent despite treatment. The number of new cases of laryngeal papillomatosis cases is approximately 4.3 cases per 100,000 children and 1.8 cases per 100,000 adults annually.

<span class="mw-page-title-main">Papilloma</span> Medical condition

A papilloma is a benign epithelial tumor growing exophytically in nipple-like and often finger-like fronds. In this context, papilla refers to the projection created by the tumor, not a tumor on an already existing papilla.

<span class="mw-page-title-main">HPV vaccine</span> Class of vaccines against human papillomavirus

Human papillomavirus (HPV) vaccines are vaccines that prevent infection by certain types of human papillomavirus (HPV). Available HPV vaccines protect against either two, four, or nine types of HPV. All HPV vaccines protect against at least HPV types 16 and 18, which cause the greatest risk of cervical cancer. It is estimated that HPV vaccines may prevent 70% of cervical cancer, 80% of anal cancer, 60% of vaginal cancer, 40% of vulvar cancer, and show more than 90% efficacy in preventing HPV-positive oropharyngeal cancers. They additionally prevent some genital warts, with the quadrivalent and nonavalent vaccines that protect against HPV types HPV-6 and HPV-11 providing greater protection.

<span class="mw-page-title-main">Gardasil</span> Human papillomavirus vaccine

Gardasil is an HPV vaccine for use in the prevention of certain strains of human papillomavirus (HPV). It was developed by Merck & Co. High-risk human papilloma virus (hr-HPV) genital infection is the most common sexually transmitted infection among women. The HPV strains that Gardasil protects against are sexually transmitted, specifically HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancers, and are responsible for most HPV-induced anal, vulvar, vaginal, and penile cancer cases. HPV types 6 and 11 cause an estimated 90% of genital warts cases. HPV type 16 is responsible for almost 90% of HPV-positive oropharyngeal cancers, and the prevalence is higher in males than females. Though Gardasil does not treat existing infection, vaccination is still recommended for HPV-positive individuals, as it may protect against one or more different strains of the disease.

Cervarix is a vaccine against certain types of cancer-causing human papillomavirus (HPV).

<span class="mw-page-title-main">Shope papilloma virus</span> Papilloma virus which infects certain leporids

The Shope papilloma virus (SPV), also known as cottontail rabbit papilloma virus (CRPV) or Kappapapillomavirus 2, is a papillomavirus which infects certain leporids, causing keratinous carcinomas resembling horns, typically on or near the animal's head. The carcinomas can metastasize or become large enough to interfere with the host's ability to eat, causing starvation. Richard E. Shope investigated the horns and discovered the virus in 1933, an important breakthrough in the study of oncoviruses. The virus was originally discovered in cottontail rabbits in the Midwestern U.S., but can also infect brush rabbits, black-tailed jackrabbits, snowshoe hares, and European rabbits.

Margaret Anne Stanley, OBE FMedSci is a British virologist and epithelial biologist. She attended the Universities of London, Bristol, and Adelaide. As of 2018, she is an Emeritus Professor of Epithelial Biology in the Department of Pathology at University of Cambridge and a Fellow of the Academy of Medical Sciences. She is also an Honorary Fellow of the UK Royal College of Obstetricians and Gynaecologists and an honorary fellow of Christ's College, Cambridge. Stanley is a research scientist in the field of virology with particular focus on the human papillomavirus (HPV). Her research work has led to new scientific findings on HPV. Additionally, she uses her expertise on HPV to serve on multiple different advisory committees and journal editorial boards.

<span class="mw-page-title-main">Harald zur Hausen</span> German virologist and professor emeritus (born 1936)

Harald zur Hausen NAS EASA APS is a German virologist and professor emeritus. He has done research on cervical cancer and discovered the role of papilloma viruses in cervical cancer, for which he received the Nobel Prize in Physiology or Medicine 2008.

HspE7 is an investigational therapeutic vaccine candidate being developed by Nventa Biopharmaceuticals for the treatment of precancerous and cancerous lesions caused by the human papillomavirus (HPV). HspE7 uses recombinant DNA technology to covalently fuse a heat shock protein (Hsp) to a target antigen, thereby stimulating cellular immune system responses to specific diseases. HspE7 is a patented construct consisting of the HPV Type 16 E7 protein and heat shock protein 65 (Hsp65) and is currently the only candidate using Hsp technology to target the over 20 million Americans already infected with HPV.

William "Bill" Fleming Hoggan Jarrett, RCVS, FRCPath, FRCPG, FRS (1928–2011) was a British pathologist.

Lutz Gissmann is a German virologist and was head of the Division “Genome Modifications and Carcinogenesis” at the German Cancer Research Center (DKFZ) in Heidelberg until his retirement in 2015. Lutz Gissmann is known for his seminal research in the field of human papillomaviruses (HPV) and their causal association with human cancer, especially cervical cancer. In his early work, he demonstrated genetic heterogeneity among HPV isolates leading the way to the now well-established concept of distinct HPV types of which some are associated with specific benign or malignant disease. In the early 1980s in the laboratory of later Nobel Prize laureate Harald zur Hausen he was the first to isolate and characterize HPV16 and HPV18, the two most oncogenic HPV types causing the vast majority of HPV-induced anogenital and head-and-neck cancers. This groundbreaking work of Lutz Gissmann provided experimental evidence for the causal association of specific HPV types with human cancer, and laid the foundation for the development of prophylactic HPV vaccines for the prevention of cervical cancer and other HPV-induced cancers. His current research interest is on development of second generation prophylactic and therapeutic HPV vaccines.

Deltapapillomavirus is a genus of viruses, in the family Papillomaviridae. Ruminants serve as natural hosts. There are seven species in this genus. Diseases associated with this genus include: warts of the skin and alimentary tract ; possibly responsible for the skin tumour equine sarcoid in horses and donkeys.

Human papillomavirus (HPV)-associated oropharyngeal cancer awareness and prevention is a vital concept from a public and community health perspective.

Gérard Orth was born on February 7, 1936, in Paris is a French virologist, emeritus research director at the CNRS, honorary professor at the Pasteur Institute.

<span class="mw-page-title-main">HPV Prevention and Control Board</span>

The HPV Prevention and Control Board, founded in 2015, is an independent group of international experts that bring together key professionals, groups and government officials to deal with issues related to screening and prevention programmes for human papillomavirus (HPV) infection, the persistence of which may lead to cervical cancer, the second most common cancer in women living in low-resource settings. The Board focusses on preventing cervical cancer in these countries by promoting the sharing of information on cervical screening and HPV vaccination, which by 2014 had reached only around 3% of eligible girls in low income countries.

References

  1. 1 2 3 "ICTV Taxonomy history: Bovine papillomavirus 1". International Committee on Taxonomy of Viruses (ICTV). Retrieved 17 January 2019.
  2. 1 2 3 4 Shah KV, Howley PM (1996). "Papillomaviruses". In Fields BN, Knipe DM, Howley PM, et al. (eds.). Fields Virology (3rd ed.). Lippincott-Raven.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Campo, MS (2006). "Bovine papillomavirus: old system, new lessons?". In Campo, MS (ed.). Papillomavirus Research: From Natural History to Vaccine and Beyond. Caister Academic. ISBN   978-1-904455-04-2.
  4. ↑ Modis Y, Trus BL, Harrison SC (2002). "Atomic model of the papillomavirus capsid". EMBO J. 21 (18): 4754–62. doi:10.1093/emboj/cdf494. PMC   126290 . PMID   12234916.
  5. ↑ Ogawa T, Tomita Y, Okada M, Shinozaki K, Kubonoya H, Kaiho I, Shirasawa H (2004). "Broad-spectrum detection of papillomaviruses in bovine teat papillomas and healthy teat skin". J. Gen. Virol. 85 (Pt 8): 2191–7. doi: 10.1099/vir.0.80086-0 . PMID   15269358.
  6. 1 2 Campo, MS (1995). "Infection by bovine papillomavirus and prospects for vaccination". Trends Microbiol. 3 (3): 92–7. doi:10.1016/s0966-842x(00)88889-7. PMID   7773594.
  7. 1 2 3 4 5 6 7 "Veterinary Manual".
  8. ↑ "Veterinary Manual".
  9. ↑ Jarrett WF, McNeil PE, Grimshaw WT, Selman IE, McIntyre WI (1978). "High incidence area of cattle cancer with a possible interaction between an environmental carcinogen and a papilloma virus". Nature. 274 (5668): 215–7. Bibcode:1978Natur.274..215M. doi:10.1038/274215a0. PMID   210386. S2CID   4172497.
  10. ↑ Syrjänen KJ (2002). "HPV infections and oesophageal cancer". J. Clin. Pathol. 55 (10): 721–8. doi:10.1136/jcp.55.10.721. PMC   1769774 . PMID   12354793.
  11. 1 2 3 4 5 Chambers G, Ellsmore VA, O'Brien PM, Reid SW, Love S, Campo MS, Nasir L (2003). "Association of bovine papillomavirus with the equine sarcoid". J. Gen. Virol. 84 (Pt 5): 1055–62. doi: 10.1099/vir.0.18947-0 . PMID   12692268.
  12. ↑ Boiron M, Levy JP, Thomas M, Friedmann JC, Bernard J (1964). "Some properties of Bovine papilloma virus". Nature. 201 (4917): 423–4. Bibcode:1964Natur.201..423B. doi:10.1038/201423a0. PMID   14110027. S2CID   4276918.
  13. ↑ Robl MG, Olson C (1968). "Oncogenic action of bovine papilloma virus in hamsters". Cancer Res. 28 (8): 1596–604. PMID   4300248.
  14. ↑ "Veterinary Manual".
  15. ↑ "HPV Symptoms, Treatment, Vaccine, HPV in Men and Women". www.std-gov.org. 2015-05-09.
  16. ↑ Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER (2007). "Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep. 56 (RR-2): 1–24. PMID   17380109.
  17. ↑ Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski B, Roteli-Martins CM, Jenkins D, Schuind A, Costa Clemens SA, Dubin G (2006). "Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial". Lancet. 367 (9518): 1247–55. doi: 10.1016/S0140-6736(06)68439-0 . PMID   16631880. S2CID   18685310.
  18. ↑ Davidson EJ, Faulkner RL, Sehr P, Pawlita M, Smyth LJ, Burt DJ, Tomlinson AE, Hickling J, Kitchener HC, Stern PL (2004). "Effect of TA-CIN (HPV 16 L2E6E7) booster immunisation in vulval intraepithelial neoplasia patients previously vaccinated with TA-HPV (vaccinia virus encoding HPV 16/18 E6E7)". Vaccine. 22 (21–22): 2722–9. doi:10.1016/j.vaccine.2004.01.049. PMID   15246603.
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