The Shope Papillomavirus (SPV), also known as cottontail rabbit papillomavirus (CRPV), is a historically important viral agent affecting rabbits. This virus gained recognition for its distinctive ability to induce horn-like growths on the skin of its hosts. The study of SPV significantly advanced the understanding of how viruses can contribute to the development of cancer. Its unique characteristics made it a foundational model in virology and oncology.
The Virus’s Discovery and Nature
The Shope Papillomavirus was first identified by Richard E. Shope in 1933. Hunters in northwestern Iowa reported observing rabbits with unusual horn-like protrusions on their bodies, prompting Shope’s investigation. He successfully isolated a filterable infectious agent from these growths, demonstrating its transmissible nature and establishing one of the first mammalian tumor virus discoveries.
SPV is classified as a papillomavirus, belonging to the family Papillomaviridae. This family of viruses is known for infecting epithelial tissues and causing benign growths like warts. The genetic material of SPV is a double-stranded circular DNA molecule, approximately 8,000 base pairs in length.
The virus itself is non-enveloped, meaning it lacks an outer lipid membrane, with its genetic material encased within a protein shell called a capsid. This capsid is composed primarily of 72 star-shaped units made from a single viral protein, L1, and a less abundant L2 protein. The overall organization of the SPV genome is similar to other papillomaviruses, featuring early (E) and late (L) genes.
How It Affects Rabbits
The Shope Papillomavirus primarily infects cottontail rabbits, with the Eastern cottontail being its main natural host. The infection manifests as horn-like warts or papillomas on the skin. These lesions often appear as raised, red, and rough patches, typically circular and exceeding one centimeter.
Growths are often observed on the upper half of the rabbit’s body, including the face, neck, shoulders, eyelids, and ears. These warts are composed of densely packed tissue, and their outer surface may appear dark due to melanin pigment. While often benign, these tumors can grow large enough to impede the rabbit’s ability to eat, potentially leading to starvation.
Transmission of SPV among rabbits occurs largely through biting arthropod vectors, such as mosquitoes and ticks. Outbreaks are more common during the summer and fall seasons, when insect populations are higher. Infected rabbits may develop immunity upon re-exposure. Wild rabbits can transmit the virus to domestic rabbits, but a domestic strain usually cannot transmit it to another domestic rabbit.
Its Role in Cancer Research
The Shope Papillomavirus is one of the first viruses definitively linked to cancer in mammals. Its discovery provided groundbreaking evidence that viruses could induce tumor formation, a concept that was not widely accepted at the time. This established SPV as a model for understanding viral oncogenesis, the process by which viruses contribute to cancer development.
Studying SPV provided insights into tumor formation, observing that benign papillomas could progress to malignant squamous cell carcinomas. This progression to metastasizing carcinomas was observed in approximately 25% of infected cottontail rabbits and in up to 75% of infected domestic rabbits. These studies showed that viral genes could influence cellular growth and differentiation, leading to uncontrolled proliferation.
The research on SPV paved the way for understanding human papillomaviruses (HPVs) and their association with various human cancers, most notably cervical cancer. SPV served as an early experimental model to investigate how papillomaviruses interact with host cells and manipulate cellular pathways to promote tumor growth. This included examining the roles of viral genes, such as E6 and E7, which in human HPVs are known to inactivate tumor suppressor proteins and contribute to genomic instability. The insights derived from SPV research continue to inform current studies into viral carcinogenesis and and the development of preventive measures, like vaccines for HPV.