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, and domestic rabbits.
History
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 1655.
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 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.
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 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.