# Rabbits With Tentacles or Horns: Shope Papillomavirus Explained A wild rabbit with black, horn-like or tentacle-like growths on its head is almost certainly infected with cottontail rabbit papillomavirus, also called Shope papillomavirus. The virus causes warts that harden into keratinized spikes, and it does not infect people or dogs. Those growths are the reason the jackalope legend exists. They are also the reason the modern HPV vaccine exists, because this rabbit virus became the first animal model that proved a virus could cause cancer. This article explains what the virus is, how it spreads, what happens to infected rabbits, what to do if you find one, and why a growth that looks like a horn is a medical problem rather than a monster. This article is educational and is not a substitute for veterinary diagnosis or treatment. ## What Is Shope Papillomavirus? Shope papillomavirus is a DNA virus in the genus *Papillomavirus* that infects rabbits and produces skin tumors. Richard Shope first described it in cottontail rabbits from Kansas and Iowa in 1933, which is why the virus still carries his name [1]. The virus was the first DNA virus shown to cause tumors in any animal, and it has been studied continuously for more than ninety years [2]. The virus has been renamed several times as taxonomy caught up with the science. The official current name is *Sylvilagus floridanus* papillomavirus 1, abbreviated SfPV1, named for the eastern cottontail rabbit that serves as its primary host [2]. In the research literature it is still most often called cottontail rabbit papillomavirus, or CRPV [3]. All three names describe the same virus. Papillomaviruses are highly species specific. A papillomavirus that infects one animal species generally does not infect another, which is why only rabbit papillomaviruses can be used to study papillomavirus disease in rabbits [3]. That species barrier is the reason Shope papillomavirus is not a human health concern. ### The Growths Have a Distinct Appearance The tumors start as small warts and develop into raised, often dark, keratinized masses. In a wild desert cottontail examined in Colorado, the growths were described as large, pedunculated, dark cutaneous lesions on the abdomen plus cylindrical masses on the mouth [4]. Pedunculated means the mass sits on a stalk. The cylindrical shape is what gives the growths their tentacle or horn appearance. The growths are most often found on the head, face, neck, and around the eyes and ears, though they can appear on the abdomen and other body regions [4]. Their surface is keratin, the same protein that makes up fingernails and hair. A mature growth can be hard, black, and several centimeters long. ### Why the Growths Look Like Horns or Tentacles Keratinized papillomas grow outward because the virus drives the cells of the outer skin layer to divide. As the mass expands, the outer layers of cells die and harden into keratin, forming a rigid core. When several of these masses grow close together on a rabbit's head, they look like a crown of horns or a cluster of tentacles. The nickname "Frankenstein rabbit" comes from the same visual effect. The virus itself is not producing a horn. It is producing a wart that has matured and hardened. The distinction matters because it explains why the growth cannot simply be cut off at the base without the underlying viral infection remaining. ## How Shope Papillomavirus Spreads The virus spreads when infected skin cells or viral particles contact broken skin on another rabbit. In wild populations, biting insects and ticks are the primary mechanical vectors. An insect feeds on an infected rabbit, picks up virus on its mouthparts, then feeds on a susceptible rabbit and deposits the virus into the skin. This is why the growths cluster on the head and face, where insects land and feed most often. Direct rabbit-to-rabbit contact can also transmit the virus, particularly through abrasions, fighting wounds, or shared burrow surfaces. The virus does not survive long in the environment outside living skin, so environmental transmission is a minor route compared with insect bites and direct contact. ### Which Rabbits Are Susceptible Shope papillomavirus primarily infects cottontail rabbits in the genus *Sylvilagus*. A survey of museum specimens found symptomatic infections in eastern cottontails, desert cottontails, and mountain cottontails, while other lagomorph genera including *Brachylagus* and *Lepus* (jackrabbits and hares) showed no symptomatic infections [1]. Prevalence of symptomatic individuals was significantly higher in *Sylvilagus* than in *Lepus* [1]. Domestic rabbits (*Oryctolagus cuniculus*) are also susceptible. When the virus is introduced into domestic rabbit skin, it induces papillomas, and those papillomas progress to carcinoma in more than 80 percent of cases [5]. This high progression rate is precisely why the domestic rabbit became such a valuable cancer model. The virus is more aggressive in domestic rabbits than in its natural cottontail host, where many warts regress on their own. ### Geographic Range The virus was long thought to be confined to the US Midwest, where Shope first described it. Molecular testing of museum specimens has since detected the virus in rabbits from Nebraska, Nevada, New Mexico, Texas, and as far south as Jalisco, Mexico [1]. The oldest laboratory-confirmed case in that survey dated to Kansas in 1915, eighteen years before Shope's original description [1]. The true range is probably broader than the historical record suggests, limited mainly by where cottontail populations and suitable insect vectors overlap. ## What Happens to an Infected Rabbit The course of infection varies widely, and the outcome depends on the rabbit's species, immune response, and viral subtype. ### Regression Many warts in wild cottontails regress spontaneously. The rabbit's immune system recognizes the viral proteins and mounts a cellular immune response that destroys the infected cells. Regression is more common in cottontails than in domestic rabbits, and it is more common with certain viral subtypes than others. Viral genetics influence this outcome. When researchers altered rare codons in the viral E6 and E7 oncogenes to make them more mammalian-like, the oncogenic potential of some mutant genomes increased dramatically, and spontaneous regression also increased as more codon changes accumulated [6]. This suggests that how efficiently the virus produces its oncoproteins shapes whether the host immune system can clear the infection. Host genetics matter too. In domestic rabbits homozygous for a specific haplotype of the DRA and DQA genes of the major histocompatibility complex, warts induced by one viral subtype showed early regression, while warts induced by another subtype persisted and evolved into carcinomas [7]. The same virus can behave differently in different rabbits. ### Malignant Progression When a wart does not regress, it can transform into squamous cell carcinoma. This is the central danger of the infection. In domestic rabbits infected with CRPV, more than 80 percent of papillomas progress to carcinoma [5]. The progression involves the viral E6 and E7 oncoproteins interfering with normal cell cycle control. CRPV E7 binds the tumor suppressor protein pRB, the same target as human papillomavirus E7 [8]. CRPV E6 proteins interact with the hDlg/SAP97 tumor suppressor, the mammalian homolog of the *Drosophila* discs large protein, though unlike HPV E6 they do not bind p53 [8]. CRPV E6 also downregulates the Notch signaling pathway through interaction with MAML1, a mechanism shared with cutaneous beta HPV types [9]. These molecular interactions allow infected cells to keep dividing when they should stop. Once a papilloma becomes a carcinoma, it can invade surrounding tissue. Gene expression profiling of CRPV-induced carcinomas identified upregulated genes directly involved in stroma invasion, including 14-3-3 zeta, YB-1, calpain 2, and thymosin beta [10]. The tumor is no longer a surface wart. It is a cancer with the ability to spread locally. ## Distinguishing Shope Papillomavirus From Other Rabbit Skin Viruses Not every rabbit skin growth is Shope papillomavirus. Several distinct viruses produce different lesions, and the distinction matters for prognosis and for what an owner should expect. ### Shope Fibroma Virus Shope fibroma virus is a poxvirus, not a papillomavirus, and it produces firm, rounded, subcutaneous nodules rather than keratinized surface growths. Fibromas are typically smooth and fleshy, not black and horn-like. They also tend to regress on their own and rarely become malignant. A rabbit with a smooth lump under the skin is more likely to have a fibroma than a papilloma. ### Rabbit Oral Papillomavirus Rabbit oral papillomavirus produces small, benign warts on the underside of the tongue and the oral mucosa. These warts are typically not visible without opening the rabbit's mouth, and they rarely cause clinical signs. They do not progress to carcinoma. A rabbit with visible horn-like growths on the head does not have oral papillomavirus. ### The Key Distinguishing Features | Feature | Shope papillomavirus (CRPV/SfPV1) | Shope fibroma virus | Rabbit oral papillomavirus | |--|--|--|--| | Virus family | Papillomavirus | Poxvirus | Papillomavirus | | Typical location | Head, face, neck, abdomen | Subcutaneous, any site | Underside of tongue, oral mucosa | | Appearance | Dark, keratinized, horn-like or tentacle-like | Smooth, fleshy, rounded nodule | Small, flat, pale warts | | Progression to cancer | Common, especially in domestic rabbits | Rare | Does not occur | | Zoonotic risk | None | None | None | | Primary hosts | Cottontail rabbits, domestic rabbits | Rabbits | Rabbits | The visual difference is usually enough for a veterinarian to make a presumptive diagnosis, though confirmation requires biopsy or molecular testing. ## What to Do If You See a Rabbit With Horns If you find a wild cottontail with visible growths, the correct response depends on whether the rabbit appears otherwise healthy. ### Observe From a Distance Do not attempt to catch, handle, or treat a wild rabbit yourself. Wild cottontails are highly stressed by capture, and handling can cause fatal stress responses. Observe from a distance and note the rabbit's behavior. A rabbit that is eating, moving normally, and maintaining body condition is coping with the infection, and many of these rabbits will eventually regress the warts on their own. ### Contact a Wildlife Professional If the rabbit appears debilitated, is unable to eat, has growths obstructing its eyes or mouth, or is showing other signs of distress, contact your state wildlife agency or a licensed wildlife rehabilitator. They can assess whether intervention is appropriate. In many jurisdictions, it is illegal to possess or treat wild rabbits without a permit. ### Protect Your Domestic Rabbits If you keep domestic rabbits, keep them indoors or in insect-screened enclosures. The virus spreads through biting insects, so mosquito and tick control is the practical prevention measure. Do not bring a wild rabbit into contact with your domestic rabbits. Do not use the same equipment for wild and domestic rabbits without disinfecting it. ### If Your Domestic Rabbit Develops Growths Domestic rabbits with new skin growths should be seen by a veterinarian promptly. Because CRPV progresses to carcinoma in the majority of domestic rabbit infections [5], early evaluation gives the best chance of successful treatment. A veterinarian will examine the growth, possibly take a biopsy, and discuss options. Treatment approaches studied in the CRPV model include surgical removal and, in research settings, RNA interference targeting the viral E6 and E7 oncogenes, which reduced tumor cell viability, migration, and proliferation in laboratory studies [11]. Any treatment decision for a pet rabbit should be made by a veterinarian who has examined the animal. ## The Jackalope Legend The jackalope is a mythical creature from American folklore, described as a rabbit with antelope horns. The legend almost certainly grew from sightings of rabbits infected with Shope papillomavirus. A cottontail with a cluster of black keratinized growths on its head looks, at a glance, like a rabbit with antlers. The virus has been found in museum specimens dating back to 1915, well before the jackalope legend became widespread in the 1930s [1]. Hunters and trappers in the American West would have encountered infected rabbits regularly. The visual resemblance between a papilloma cluster and a set of small horns is close enough that the connection is difficult to dismiss. No rabbit naturally grows antlers. The growths are tumors, and they cause the rabbit real harm. The folklore is entertaining, but the underlying disease is not. ## How This Rabbit Virus Changed Cancer Science Shope papillomavirus is one of the most consequential viruses in the history of cancer research. Its discovery in 1933 established that a virus could cause cancer in an animal, a finding that eventually led to the recognition that viruses cause several human cancers. ### The First Cancer Virus Model CRPV was the first DNA virus shown to be tumorigenic [2]. For decades afterward, it served as the primary model for studying how papillomaviruses cause cancer. The virus induces papillomas that progress to squamous cell carcinoma at a high rate in domestic rabbits, which makes it possible to study the entire arc of infection, wart formation, and malignant transformation in a single animal [3]. ### The VX2 Carcinoma Model A particularly important derivative of CRPV research is the VX2 carcinoma, a transplantable tumor line derived from a CRPV-induced carcinoma in a New Zealand [White rabbit](/knowledge/veterinary-medicine/small-mammal-care/rabbit-lifespan-and-aging-caring-for-senior-rabbits). VX2 tumors are used as a model for human head and neck squamous cell carcinoma, and they allow researchers to test treatments that might eventually be used in people [3]. The VX2 line has been cultured for up to 150 passages and remains a workhorse of papillomavirus cancer research [11]. ### The HPV Vaccine Connection The CRPV model played a direct role in the development of the HPV vaccines now used to prevent cervical cancer and other HPV-associated cancers. The SfPV1/rabbit model was used to study viral-host interactions and to test prophylactic virus-like particle vaccines, and it contributed to the successful development of three such vaccines [2]. The principle that a papillomavirus could be prevented by vaccination was established in rabbits before it was applied to humans. ### What the Model Taught About Viral Oncogenes CRPV research clarified how papillomaviral oncogenes work. The virus encodes three transforming proteins, LE6, SE6, and E7, and each is required for papilloma formation [8]. The E2 protein is essential for tumor induction, and mutations that abolish its transactivator function prevent tumor formation entirely [5]. The E1 and E2 proteins regulate each other's subcellular localization, which controls viral replication [12]. These findings in rabbits translated directly to understanding HPV. The model also revealed that viral transcription patterns do not necessarily change during malignant progression. A comparison of CRPV transcripts in papillomas versus carcinomas found no qualitative or quantitative differences in viral transcription between the two stages [13]. The virus does not need to change its gene expression to drive cancer. It needs only to keep expressing the same oncogenes in the same cells. ## What Is Still Uncertain Several questions about Shope papillomavirus remain open. The exact prevalence in wild cottontail populations is not well characterized, and the museum specimen survey that detected the virus in new states was limited by which specimens happened to be preserved [1]. The true geographic range and the frequency of different viral strains in the wild are not fully mapped. The molecular details of how CRPV E6 proteins contribute to cancer are still being worked out. Unlike HPV E6, CRPV E6 does not bind p53, so the mechanism by which it promotes malignancy differs from the human virus [8]. The interaction with hDlg/SAP97 and the downregulation of Notch signaling through MAML1 are two known mechanisms, but others may exist [9]. The role of host genetics in determining whether a wart regresses or progresses is understood in outline but not in detail. The MHC haplotype association is clear, but the full set of host genes that influence outcome has not been identified [7]. Treatment options for infected domestic rabbits are limited. Surgical removal is the standard approach for accessible growths, but the virus remains in the skin, and new growths can appear. The RNA interference approach studied in the laboratory has not yet been developed into a clinical treatment for pet rabbits [11]. ## Limitations and When to Contact a Veterinarian This article describes the general biology of Shope papillomavirus and the typical course of infection. Individual rabbits vary, and a veterinarian who examines your rabbit can give you specific guidance that this article cannot. Contact a veterinarian promptly if your domestic rabbit develops any new skin growth, especially a dark, raised, or keratinized mass on the head or face. Also contact a veterinarian if an existing growth changes in size, bleeds, ulcerates, or appears to cause the rabbit pain or difficulty eating. Because CRPV progresses to carcinoma in the majority of domestic rabbit infections [5], early evaluation is the most important step an owner can take. For wild rabbits, contact your state wildlife agency or a licensed wildlife rehabilitator if the animal appears debilitated or unable to function normally. Do not attempt to treat a wild rabbit yourself. ## Frequently Asked Questions ### Can a rabbit with horns or tentacles infect my dog? No. Shope papillomavirus is highly species specific and does not infect dogs. Papillomaviruses generally do not cross species barriers, which is why only rabbit papillomaviruses can be used to study papillomavirus disease in rabbits [3]. Your dog cannot catch the virus from a wild rabbit. ### Can I catch Shope papillomavirus from a wild rabbit? No. The virus does not infect humans. It is a rabbit papillomavirus, and papillomaviruses are species specific [3]. You should still avoid handling wild rabbits, but the reason is the rabbit's welfare and the risk of other infections, not Shope papillomavirus. ### What causes the black horn-like growths on a rabbit's head? Cottontail rabbit papillomavirus causes the growths. The virus drives skin cells to divide, and the resulting wart matures into a hardened keratin mass. The growths cluster on the head because biting insects, which spread the virus, feed most often on the face and ears [4]. ### Do the growths always turn into cancer? No. Many warts in wild cottontails regress on their own when the rabbit's immune system clears the infection. In domestic rabbits, however, more than 80 percent of CRPV-induced papillomas progress to carcinoma [5]. The outcome depends on the rabbit's species, immune response, and the viral subtype. ### Is Shope papillomavirus the same as Shope fibroma virus? No. They are different viruses. Shope papillomavirus is a papillomavirus that causes keratinized, horn-like growths that can become cancerous. Shope fibroma virus is a poxvirus that causes smooth, fleshy nodules that rarely become malignant. The two are often confused because both are named after Richard Shope. ### Did Shope papillomavirus lead to the HPV vaccine? Yes, in part. The CRPV rabbit model was used to study viral-host interactions and to test prophylactic virus-like particle vaccines, and it contributed to the successful development of three HPV vaccines now in use [2]. The principle that papillomavirus infection could be prevented by vaccination was established in rabbits first. ### What should I do if I see a wild rabbit with these growths? Observe from a distance and do not handle the rabbit. If the rabbit appears healthy and is eating and moving normally, it is likely coping with the infection and may regress the warts on its own. If it appears debilitated, contact your state wildlife agency or a licensed wildlife rehabilitator. ### Can my domestic rabbit catch Shope papillomavirus? Yes. Domestic rabbits are susceptible to CRPV, and the virus progresses to cancer at a high rate in them [5]. Keep domestic rabbits indoors or in insect-screened enclosures to reduce exposure to biting insects, and do not allow contact with wild rabbits. If your domestic rabbit develops a skin growth, see a veterinarian promptly. ## Related Articles - [Grooming Your Pet Rabbit](/knowledge/veterinary-medicine/small-mammal-care/rabbit-grooming) - [Diet Of A Rabbit](/knowledge/veterinary-medicine/nutrition/diet-of-a-rabbit) - [Rabbit Behavior Training](/knowledge/veterinary-medicine/behavior/rabbit-behavior-training) - [Rabbit Litter Training](/knowledge/veterinary-medicine/behavior/rabbit-litter-training) - [Rabbit Chewing Wood](/knowledge/veterinary-medicine/behavior/rabbit-chewing-wood) - [Rabbit Care Guide for New Owners](/knowledge/veterinary-medicine/small-mammal-care/rabbit-care) - [Rabbit Poop Guide: Normal Droppings, Cecotropes, and Warning Signs](/knowledge/veterinary-medicine/small-mammal-care/rabbit-poop-guide-normal-droppings-and-cecotropes) - [Rabbit Dewlap: What It Is, What Is Normal, and Problems](/knowledge/veterinary-medicine/small-mammal-care/rabbit-dewlap-what-is-normal) - [Can Rabbits Get Rabies? 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