Shope papilloma virus

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Shope papilloma virus
Rabbit shopes papilloma virus 3.jpg
Rabbit with Shope papillomavirus infection
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Monodnaviria
Kingdom: Shotokuvirae
Phylum: Cossaviricota
Class: Papovaviricetes
Order: Zurhausenvirales
Family: Papillomaviridae
Genus: Kappapapillomavirus
Species:
Kappapapillomavirus 2
Synonyms [1]
  • Rabbit papilloma virus
  • Rabbit (Shope) papilloma virus
  • Cottontail rabbit papillomavirus (Shope)
  • Cottontail rabbit papillomavirus

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, European rabbits, [2] and domestic rabbits. [3]

Contents

History

Richard Edwin Shope discovered the Shope papillomavirus Richard Edwin Shope.jpg
Richard Edwin Shope discovered the Shope papillomavirus
Engraving from Tableau Encyclopedique et Methodique, 1789. Lepus cornutus.jpg
Engraving from Tableau Encyclopedique et Methodique, 1789.

In the 1930s, hunters in northwestern Iowa reported that the rabbits they shot had several "horn" protrusions on many parts of their bodies including their faces and necks. [4] The virus is also a possible source of myths about the jackalope, a rabbit with the horns of an antelope, and related cryptids such as the wolpertinger. Stories and illustrations of horned rabbits appear in scientific treatises dating back many years, such as the Tableau encyclopédique et méthodique , from 1655. [5]

The Iowa reports led cancer researcher Richard E. Shope to investigate, and he discovered the virus in 1933. [6] He separated the virus from horny warts on cottontail rabbits and made one of the first mammalian tumor virus discoveries. [6] Shope determined the protrusions were keratinous carcinomas due to the infection of CRPV. Shope's research led to the development of the first mammalian model of cancer caused by a virus. He was able to isolate virus particles from tumors on captured animals and use these to inoculate domestic rabbits, which then developed similar tumors. This has contributed to our understanding of fundamental mechanisms in neoplasia, or the formation of a new, abnormal growth of tissue. [6] The virus was sequenced in 1984, showing substantial sequence similarities to HPV1a. It has been used as a model for human papillomaviruses both before and after this discovery. The most visible example of this role is the HPV vaccine, which was developed based on and incorporating research done using the virus as a model. Similarly, it has been used to investigate antiviral therapies. [7]

Genome

There is a lack of specific data about the reproductive cycle of papillomaviruses. Research is not conclusive about which coding regions are expressed before or after replication of viral DNA. E1 is the largest open reading frame, which is the set of codons in the genome that code for proteins, encoding a 602 base protein. E1 is similar to COOH-terminal domain of the Simian virus 40, plays a role in viral DNA replication maintaining plasmids within a cell. Results have found that CRPV and BPV1 are found in the same location of the genome, which indicates that papillomaviruses likely have similar methods of replicating their genomes outside of a chromosome. A notable difference between the genomes of the four strains is that the E6 protein is almost twice as long in the CRPV as in any of the other strains of papillomaviruses. The E6 protein is somewhat homologous[ clarification needed ] with a family of ATP syntheses that are found in mitochondria of cattle. The homology is significant enough to imply an evolutionary relationship between E6 and the beta chain of the ATP synthase family; however, they do not have the same function or enzyme activity. The E2 protein overlaps with the E4 open reading frames in the other papillomaviruses. These differences in the E2 proteins likely determine how oncogenic a virus is. The noncoding region has a homologies with BPV1. Other homologies exist, such as the fact that all papillomaviruses have repeated sequences in the noncoding parts of their genomes. CRPV has some notable repeats, some as long as 32 base pairs. Many pairs up stream of the transcription locations are homologous with promoter sequences in of SV40. [8]

Life cycle

Replication cycle and transcription

The papillomavirus life cycle begins with cells actively multiplying in epithelial cells of basal and parabasal layers. The differentiation of these cells is necessary for this virus to complete its life cycle. Transforming proteins E6 and E7 induce the S-phase in the lower epithelial layers. [9] Viral replication proteins E1 and E2 are also required to form the papilloma and keep the episomal viral genome replication low. Genome amplification will be restrained until viral replication proteins increase and several viral proteins are co-expressed. The infected, differentiating cells travel towards the epithelial surface during the viral cycle's late stage. In the upper epithelial layers, the promoter activity is altered during the virus’ production. E4 proteins are expressed, and viral DNA amplification starts in the differentiated cells. Following this, the L1 and L2 viral capsid proteins are expressed, and the infectious virions begin to assemble. [10]

Expression of the papillomavirus E4 protein correlates with the onset of viral DNA amplification. Using a mutant cottontail rabbit papillomavirus (SPV) genome incapable of expressing the viral E4 protein, it has been shown that E4 is required for the productive stage of the SPV life cycle in New Zealand White and cottontail rabbits. [9]

Assembly and release

The virus particles are assembled in the upper epithelium. The virus capsomere icosahedral shell is packaged with an 8000 base pair genome, 360 L1 protein copies, and 12 copies of L2 proteins inside. L2 proteins gather at PML body nuclear structures and recruit L1 proteins during virus assemblage. L2 proteins are not necessary for assemblage, but it is possible that they augment packaging and infectivity. Capsid proteins have been thought to also gather at the PML bodies during packaging. [9]

Transmission of the Papillomavirus requires release from the infected skin cell at the epithelial surface, as they are non-lytic. They are resistant to desiccation, enhancing their survivability during extracellular transfer between hosts. Cornified squame release from the surface of epithelial cells may also contribute to their survival. Immune detection of the virus in the host may also be hindered by antigen retention until the virus reaches upper epithelial cells. [9]

Modulation of host processes

When Richard E. Shope began his research on SPV, little was known about the natural transmission of the virus vectors and interactions of the virus on its hosts. In the lab setting, Shope worked with the virus’ natural host, the cottontail rabbit. [6] Particularly, he worked with the cottontails of Iowa and other western states of the United States. He worked with these species because it was discovered that SPV had a restricted geographic range and was confined to the high plains of the western United States. [6] Therefore, the major host species of SPV is the cottontail rabbit of the western United States. Cottontail rabbits in Shope's lab usually were infected with the virus through parasites such as rabbit ticks. [6] When infected with SPV, hosts develop papillomas on hair-bearing skin, usually around the face and neck. [6] Shope found through his research that rabbit epidermal cell transformation by SPV requires interaction with mesenchymal cells. It was further found that mesenchymal types support papillomatous transformation. [6] Shope's research also investigated how vitamin A deficiencies or excess might affect host susceptibility to SPV. Shope found that deficiencies in vitamin A did not affect the relative growth of the papillomas, but in cases where there was excesses of vitamin A Shope papillomas were inhibited. [6] Therefore, when SPV infects a host, vitamin A plays an important role in the host/virus interactions.[ citation needed ]

Location in the host

Fluorescent antibody study identified the locations of viral antigens in wild rabbit papillomas. They were present only in the nucleus of keratohyaline and keratinized layer cells, and not deeper down in proliferating epithelial cells. In domesticated rabbits, the viral antigens were present in much smaller quantity in only superficial, keratinized layers. The investigation proposed that the virus is only present in proliferating cell nuclei during early development, containing a deficient number of proteins and mostly nucleic acid. The proteins may be immunologically specific in order to keep its transmissibility, making it a masked virus. [11]

Associated viruses

Most homologous papillomaviruses are actually CRPV and HPV1a. This is possibly because both of these viruses target the skin. From an evolutionary perspective, CRPV and HPV1a could have diverged recently, or they could have converged due to their similar target. CRPV is a member of the papillomaviruses so it is related to all viruses in this family. [8]

Tropism

Infection of a rabbit's follicular cell often occurs in locations including ears, nose, eyelids, and the anus. The infection first appears as a red and swollen area on the skin, followed by development of circular papilloma warts and keratinized horny warts. Although transmission between rabbits is high, the tumors themselves do not contain the infectious virus. 25% of Papilloma infections become malignant and form squamous cell carcinoma. Metastases can form in the lungs and lymph nodes, and if it advances further, can develop in the kidneys and the liver. [2]

Rabbit Papilloma displays tropism for the cutaneous epithelium. Warts are made up of nearly homogenous vertical tissue strands. Their outer coloration is typically black or greyish, and cut sections are usually white or pinkish white with a flesh-like center. Dark coloration is due to abundant melanin pigment. The warts are made up of several tight, branching, threadlike epidermis processes connected by narrow tissue cores. These growth structures indicate that the growth occurs simultaneously at several different centers, causing the surrounding tissue to bulge from the growth's lateral pressure. The normal epithelium abruptly transitions into a narrow zone of rapidly thickening epithelial layers, made up of rapidly multiplying cells. [4]

Rabbits re-infected with the virus exhibit some or complete immunity, and can transmit the virus to other wild rabbits, and from wild to domestic rabbits. A domestic strain cannot transmit it to another domestic rabbit, however. [4]

Immunologically, the papillomatosis virus is not related to fibroma or myxoma in rabbits. [4]

See also

Related Research Articles

<span class="mw-page-title-main">DNA virus</span> Virus that has DNA as its genetic material

A DNA virus is a virus that has a genome made of deoxyribonucleic acid (DNA) that is replicated by a DNA polymerase. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and those that have one strand of DNA in their genome, called single-stranded DNA (ssDNA) viruses. dsDNA viruses primarily belong to two realms: Duplodnaviria and Varidnaviria, and ssDNA viruses are almost exclusively assigned to the realm Monodnaviria, which also includes some dsDNA viruses. Additionally, many DNA viruses are unassigned to higher taxa. Reverse transcribing viruses, which have a DNA genome that is replicated through an RNA intermediate by a reverse transcriptase, are classified into the kingdom Pararnavirae in the realm Riboviria.

<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 all 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">Epstein–Barr virus</span> Virus of the herpes family

The Epstein–Barr virus (EBV), formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. Epstein-Barr virus (EBV) is the first identified oncogenic virus, which establishes permanent infection in humans. EBV causes infectious mononucleosis and is also tightly linked to many malignant diseases. Various vaccine formulations underwent testing in different animals or in humans. However, none of them was able to prevent EBV infection and no vaccine has been approved to date.

<i>Hepadnaviridae</i> Family of viruses

Hepadnaviridae is a family of viruses. Humans, apes, and birds serve as natural hosts. There are currently 18 species in this family, divided among 5 genera. Its best-known member is hepatitis B virus. Diseases associated with this family include: liver infections, such as hepatitis, hepatocellular carcinomas, and cirrhosis. It is the sole accepted family in the order Blubervirales.

<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.

<i>Polyomaviridae</i> Family of viruses

Polyomaviridae is a family of viruses whose natural hosts are primarily mammals and birds. As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus. 14 species are known to infect humans, while others, such as Simian Virus 40, have been identified in humans to a lesser extent. Most of these viruses are very common and typically asymptomatic in most human populations studied. BK virus is associated with nephropathy in renal transplant and non-renal solid organ transplant patients, JC virus with progressive multifocal leukoencephalopathy, and Merkel cell virus with Merkel cell cancer.

<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">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">Viral transformation</span>

Viral transformation is the change in growth, phenotype, or indefinite reproduction of cells caused by the introduction of inheritable material. Through this process, a virus causes harmful transformations of an in vivo cell or cell culture. The term can also be understood as DNA transfection using a viral vector.

<span class="mw-page-title-main">Bovine papillomavirus</span> Group of viruses

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 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.

<i>Plasmaviridae</i> Family of viruses

Plasmaviridae is a family of bacteria-infecting viruses. Acholeplasma species serve as natural hosts. There is one genus in the family, Plasmavirus, which contains one species: Acholeplasma virus L2. All viruses known in this family have been isolated from species in the class Mollicutes.

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.

<span class="mw-page-title-main">Richard Shope</span> American physician

Richard Edwin Shope was an American virologist who, together with his mentor Paul A. Lewis at the Rockefeller Institute, identified influenzavirus A in pigs in 1931. Using Shope's technique, Smith, Andrewes, and Laidlaw of England's Medical Research Council cultured it from a human in 1933. They and Shope in 1935 and 1936, respectively, identified it as the virus circulating in the 1918 pandemic. In 1933, Shope identified the Shope papilloma virus, which infects rabbits. His discovery later assisted other researchers to link the papilloma virus to warts and cervical cancer. He received the 1957 Albert Lasker Clinical Medical Research Award and was an elected member of the United States National Academy of Sciences, the American Philosophical Society, and the American Academy of Arts and Sciences.

Bandicoot papillomatosis carcinomatosis virus is a circular double-stranded DNA virus isolated from bandicoots. The genome has features similar to viruses in the families Papillomaviridae and the Polyomaviridae. Two species have been described to date.

Epsilonpapillomavirus is a genus of viruses in the family Papillomaviridae. Cattle serve as the natural hosts of these bovine papillomaviruses. There are two species in this genus. Diseases associated with this genus include fibropapillomas and true epithelial papillomas of the skin.

<span class="mw-page-title-main">Large tumor antigen</span>

The large tumor antigen is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. LTag is expressed early in the infectious cycle and is essential for viral proliferation. Containing four well-conserved protein domains as well as several intrinsically disordered regions, LTag is a fairly large multifunctional protein; in most polyomaviruses, it ranges from around 600-800 amino acids in length. LTag has two primary functions, both related to replication of the viral genome: it unwinds the virus's DNA to prepare it for replication, and it interacts with proteins in the host cell to dysregulate the cell cycle so that the host's DNA replication machinery can be used to replicate the virus's genome. Some polyomavirus LTag proteins - most notably the well-studied SV40 large tumor antigen from the SV40 virus - are oncoproteins that can induce neoplastic transformation in the host cell.

Gérard Orth was a French virologist, emeritus research director at the CNRS, honorary professor at the Pasteur Institute.

<i>Monodnaviria</i> Realm of viruses

Monodnaviria is a realm of viruses that includes all single-stranded DNA viruses that encode an endonuclease of the HUH superfamily that initiates rolling circle replication of the circular viral genome. Viruses descended from such viruses are also included in the realm, including certain linear single-stranded DNA (ssDNA) viruses and circular double-stranded DNA (dsDNA) viruses. These atypical members typically replicate through means other than rolling circle replication.

Peter Maxwell Howley is an American pathologist, virologist, and professor at Harvard Medical School. He has been president of the American Society for Virology and the American Society for Investigative Pathology and a co-editor of the Annual Review of Pathology: Mechanisms of Disease.

Michelle Adair Ozbun is an American molecular virologist who is the Maralyn S. Budke Endowed Professor in Viral Oncology at the University of New Mexico School of Medicine. Her research considers cancer biology and how human papillomavirus infections cause pathology including their contributions to cancers.

References

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  3. "Rabbit (Shope) Papilloma Virus". dora.missouri.edu. Retrieved 14 September 2023.
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  5. "Historiae Naturalis De Quadrupetibus Libri". NYPL Public Domain Archive. January 1655.
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  8. 1 2 Giri, Isabelle; Danos, Olivier; Yaniv, Moshe (March 1985). "Genomic Structure of the Cottontail Rabbit (Shope) Papillomavirus". Proceedings of the National Academy of Sciences. 82 (6): 1580–84. Bibcode:1985PNAS...82.1580G. doi: 10.1073/pnas.82.6.1580 . PMC   397315 . PMID   2984661.
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