Shope papilloma

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 papillomaviruses and neoplasia. 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. 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. 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 1789. The Iowa reports led cancer researcher Richard E. Shope to investigate, and he discovered the virus in 1933. He separated the virus from horny warts on cottontail rabbits, and made one of the first mammalian tumor virus discoveries. 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 a 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. 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. There is a lack of specific data about the productive cycle of papillomaviruses. Research is not conclusive about which coding regions are expressed before or after replication of viral DNA. The E1 region should carried the DNA required for cis and/or trans. 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 is indicates that papillomaviruses likely have similar methods of replicating their genomes outside of a chromosome. 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 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. 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. 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. 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. 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. Transmittance 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.