Virology Unmasked

By Molly Cavanaugh, September 2025

Viruses have existed for billions of years, far before humans, or even animals, walked the earth (1). While science has just started to uncover the secrets of viruses, our ancestors noticed viruses and explained them in their own way. Plagues were explained as bad air, misbalance in the fluids of the body, and even as punishment from God (2). Viruses also explain some mystical creatures, such as the Jackalope (3). The Jackalope is a rabbit with antlers fixed on their head and super powers ranging from running up to 50 mph (80 kph) to catching bullets in their teeth (4,5).  While the powers may be fictionalized, rabbits with ‘horns’ can be seen hopping around the United States to this day.

In the early 1930s, two Wyoming brothers created something brand new- a taxidermied rabbit with horns- a Jackalope (6). These brothers brought to life a story that had been told for centuries in the American west. The first possible painting of Jackalopes was from Persia in the 13^th century and the fist conclusive painting was created in 1575 (7, 8).  The story of the Jackalope also appeared in Dutch paintings in the early 1600s (9). These paintings show the prevalence of stories about horned rabbits over hundreds of years. But horned rabbits are more than a story, these rabbits were likely suffering from Shope papilloma virus.

Shope papilloma virus (SPV), also called cottontail rabbit papillomavirus, is a virus closely related to human papillomavirus (HVP), a human virus which causes cancer (10). For a more in-depth dive into HPV, explore here (HPV Vaccine- Virology Unmasked). SPV is a double stranded DNA virus, just like HPV. While rabbits suffering from SPV rarely grow deer like antler, SPV causes cancer which presents itself as hard tumors which can resemble horns. These horns can either be cancerous or non-cancerous hard tumors. Only 25% of cases of SPV in wild rabbits progress to tumors, meaning you cannot tell if a rabbit is infected simply by looking at it (11). Outbreaks of SPV, while not atypical, are appearing across the Western and Midwest states (12, 13, 14). Although the appearance of SPV is frightening, SPV is usually not harmful to the rabbits. Importantly, SPV cannot be spread to humans. In fact, the virus cannot infect dogs, cats, or most household pets. Rabbits who are kept as pets are at risk, as well as wild hares (15). SPV is spread based on contact with the skin to skin contact, or through a carrier like ticks or misquotes (16).

SPV was discovered in 1933 and was shown to cause cancer as early as 1935. SPV was the first, but certainly not the last, double stranded DNA virus shown to cause cancer. Since 1935, the Papillomaviridae family, which contains both HPV and SPV, has been shown to infect reptiles, birds, even polar bears (17). This is a large family of viruses with a wide variety of hosts but the viruses behave in similar ways. Generally, the Papillomaviridae family induces cancer by stopping the body’s natural molecular blocks against cancer (18). The Papillomaviridae family is essential for future cancer research, with SPV having an impressive role in the fight against HPV (19). HPV is a species restricted virus, meaning that it can only infect humans. It is extremely hard to study viruses which can only infect humans, because there is no animal model to test treatments in.

There are several ways to get around the problem of human only viruses. Some scientists change the animals so that they can be infected with human viruses. For example, although HIV can only infect humans, there are now techniques that allow a human immune system to be inserted into mice so scientists can study HIV far more easily (20). When the mouse has a human immune system, HIV can infect the mouse, allowing scientists to test life saving drugs and gather data that could never be taken from people living with HIV. Another way to study human viruses, is to study animal viruses which are almost identical to human viruses to predict how the virus would behave in humans. While SPV does not infect humans, it is so close to HPV that scientists can use studies on SPV in rabbits to predict how HPV will work in humans (19).

SPV contains the same major genes- E6 and E7- that HPV uses to drive cancer in humans. Because SPV interacts with the rabbit host in a similar way to HPV, scientists can make predictions about how HPV interacts with human cells. Why is this important? An animal model like SPV allowed scientists to study the immune response at specific timepoints, ways the virus functions, and even determined that rabbits could be protected against the virus when exposed to antibodies (21). While the current HPV vaccine was not based on SPV, the development of this vaccine was informed by decades of SPV research. SPV jumpstarted a whole field of viral oncology, which we now know account for at least 10% of all cancers in the US (22).

Shope papilloma virus and the American Jackalope are great examples of how virology can impact both human stories and health. We create stories for what we can’t explain. The Jackalope started as a legend but the shope papilloma virus, the cause for the mysterious creature, was then used to unravel the secrets of human cancer. Virology has been advanced through a series of discoveries that reshaped how we think of human health. Who would think that the Jackalope would be a tool to cure human cancers?