Researchers at the University of Wisconsin School of Veterinary Medicine have identified a possible way to make longer lasting vaccines for respiratory viruses like influenza and the coronavirus that causes COVID-19.

The work, published March 25 in in the journal Cell Reports, focuses on T cells, a type of immune cell that helps control infections by killing virus-infected cells. Unlike antibodies — the basis of most current vaccines, which can lose effectiveness as viruses mutate — T cells recognize more stable parts of viruses, offering a path to broader protection.

A problem with designing vaccines around T cells, though, is their relatively short lifespan. The new research sheds light on a surprising potential workaround.

“We have discovered essentially a mechanism which we can target — a new clue to generating long-lived T cells,” says M. Suresh, a professor in the Department of Pathobiological Sciences who led the study.

Rethinking how vaccines trigger immunity

Most vaccines are designed to stimulate antibodies that block infection. That approach works well for many infectious diseases, but it can fall short against viruses that evolve quickly.

“So, what do we do? We need a plan B,” says Suresh.

For viruses like SARS-CoV-2 and seasonal influenza, that plan B has meant regularly updating vaccines to target newer virus variants and encouraging the public to get the latest flu and COVID shots each year. But that strategy has its pitfalls.

“With the pandemic we went through, people are just tired of getting vaccinated,” Suresh says. Indeed, vaccination rates have been declining in the United States for years.

The ability to harness T cells could offer a potentially more effective plan B. Rather than preventing infection outright, T cells help limit disease severity and promote early recovery by identifying and destroying infected cells.

“They go and hunt one infected cell at a time and eliminate them,” Suresh says.

Because T cells recognize internal viral proteins that don’t change much over time, they can remain effective even as viruses mutate.

A key challenge, however, is the durability of protection offered by T cells, especially in the lungs, where respiratory infections take hold.

Suresh’s lab studies a specialized group of immune cells known as tissue-resident memory T cells, which remain in the lungs and airways as a first line of defense. These cells can respond quickly to infection.

“But the problem is they don’t stay very long,” Suresh says. “They die off, and we still don’t know why.”

A different early signal, a different immune outcome

In the new study, which was funded by the National Institutes of Health, Suresh and his colleagues looked at what happens in the first hours after vaccination, when the body’s innate immune system is activated.

Different types of pathogens trigger different early inflammatory signals that “program” memory T cells to recognize and go after infected cells. Suresh’s team asked whether changing those signals could reshape how T cells develop.

Using an experimental vaccine approach in mice, the researchers compared two types of early immune signals: one that mimics a viral infection and another that resembles a bacterial response. The difference was striking.

“When we had a virus-like inflammation, the memory T cells dropped off and we quickly lost protection,” Suresh says. “But when we created a bacterial-like inflammation, the mice developed a different kind of memory T cell which actually persisted longer and protected longer.”

Stem-like cells that adapt when needed

The longer-lasting cells had characteristics similar to stem cells, Suresh says, including the ability to persist and regenerate.

Even more surprising, those cells were able to adapt when confronted with a virus. When the researchers exposed vaccinated mice to infection, the T cells shifted into a more typical virus-fighting mode.

“They just flipped,” Suresh says.

That flexibility suggests the T cells could combine durability with the ability to effectively combat a viral infection.

Toward longer-lasting, broader vaccines

The findings offer a potential path toward vaccines that require fewer boosters and provide broader protection across variants.

“The duration of immunity is really, really important,” Suresh says. “Can we vaccinate fewer times, and can shots protect against new strains?”

The research also highlights the importance of delivering immunity where infections occur. For respiratory diseases, that may mean developing vaccines that work in the nose and lungs rather than through injection.

“The best way to immunize against all our respiratory infections is to give through the normal route of infection,” Suresh says.

What comes next

The current study was conducted in mice. The team plans to test the approach in nonhuman primates and in models that better reflect the diversity of human immune systems.

Future work will also explore ways to guide immune cells to the lungs after traditional vaccination — a strategy that could improve protection without requiring new delivery methods.

This research received funding from the National Institutes of Health (U01 AI124299 and R21 AI149793).

This image of a section through the midface of a mouse embryo illustrates fusion of the tissues that form the secondary palate above the tongue. Green staining illustrates cells expressing a key enzyme that mediates DNA methylation, blue indicates nuclei of all cells, red indicates epithelial cells.

Cleft lip and palate are the most common craniofacial birth defects in humans, affecting more than 175,000 newborns around the world each year. Yet despite decades of research, it’s still not known what causes most cases or what can be done to prevent them. But a recent study from the University of Wisconsin School of Veterinary Medicine (SVM) has uncovered new information about orofacial development in mice that researchers believe could one day help reduce the risk of these birth defects in humans.

Published this week in the Proceedings of the National Academy of Sciences (PNAS) the study provides the first direct evidence of a mechanism called DNA methylation being required for craniofacial development. DNA methylation is a process where a group of molecules are added to DNA that change the expression of genes without actually altering the DNA sequence. It’s also affected by various environmental factors. The researchers discovered that disruption to DNA methylation interferes with development of the lip and palate and causes these birth defects in mice.

Rob Lipinski

Led by Robert Lipinski, associate professor of comparative biosciences at the UW School of Veterinary Medicine, the research is an important step toward developing preventive strategies that could one day lessen the risk of cleft lip and palate, known collectively as orofacial clefts (OFCs), in both animals and humans.

“We knew from past research that genetics and the environment interact to cause these types of birth defects, but our understanding of the environmental component lagged far behind that of genetics.” says Lipinski. “Unlike genetics, we don’t have a permanent record of the prenatal environment that can be examined retrospectively, but connecting OFCs to DNA methylation helps narrow our focus on the particular environmental influences that modify the risk for these types of birth defects.”

His team’s work confirmed the essential role of DNA methylation in regulating orofacial development during embryonic development and demonstrates how disruptions to that process alter the ability of stem cells to form the connective tissue of craniofacial bone and cartilage, resulting in OFCs.

Lipinski and his team arrived at these results by first genetically manipulating DNA methylation in two separate groups of mouse embryos. The experiments resulted in seemingly contradictory results, with OFCs developing in one group of mice, but not the other. To understand why there was a difference between the groups, the team conducted another round of experiments in which they inhibited DNA methylation in mouse embryos at different stages of development. The timing of when DNA methylation occurs was critical to the development of orofacial clefts.

They found that exposure on the 10th gestational day resulted in OFCs but administering the same inhibitor just 48 hours later resulted in normal orofacial development.

Identifying this narrow window of gestational sensitivity is important, Lipinski says, because it not only helps narrow the focus of the next stage of his team’s research but it will also help design future public education initiatives once more is known about the modifiable environmental and behavioral risk factors that impact OFC risk in humans.

The 10th gestational day in mouse embryos corresponds with the beginning of the 5th week of embryonic development in humans–a stage at which many pregnancies may not yet be recognized.

“We know DNA methylation can be influenced by a variety of environmental factors, including maternal stress, diet, and exposure to drugs, toxins and environmental pollutants, and having a better understanding how orofacial development is regulated by environmentally sensitive mechanisms could directly inform birth defect prevention strategies,” he says. “This next phase of our team’s research is focused on identifying specific factors that influence DNA methylation during orofacial development and which could therefore alter OFC risk.”

Lipinski and his team are uniquely positioned to pursue this next stage of research because of another important outcome of the study: a new in vitro model the team developed. The model will allow them to rapidly screen thousands of dietary and environmental factors in a laboratory dish before testing the impact of specific factors on cleft susceptibility in mouse models.

The results in cell and animal models will help the researchers more quickly and accurately identify factors likely to be of consequence to human development.

Orofacial clefts of the upper lip and palate affect approximately 1 in 700 newborns, and individuals with OFCs navigate feeding difficulties as infants that require multiple surgeries, dental procedures, and speech therapy during childhood and adolescence. Studies have shown higher mortality rates at all stages of life for individuals with OFCs.

This study was supported by funding from the National Institutes of Health under award numbers R03DE027162, R56DE030917, RO1DE032710, U01 DK11807, and R01DK099328, and T32ES007015. Additional support was also provided by the University of Wisconsin Hilldale Undergraduate Research Award.

Researchers at the University of Wisconsin–Madison have taken a novel approach to assessing canine vision. Their recent study uses a dog’s interest in a variety of video content to better measure the quality of its vision. iStock / damedeeso

Ever wonder what kind of TV shows your dog might choose if they could work the remote control? New research from the University of Wisconsin–Madison’s School of Veterinary Medicine provides some answers, but the study was more interested in solving a longstanding problem in veterinary medicine than turning canine companions into couch potatoes.

According to Freya Mowat, veterinary ophthalmologist and professor in the School of Veterinary Medicine’s department of surgical sciences, researchers wanted to determine factors, including age and vision, that influence a dog’s interest in interacting with video content. Ultimately, the goal of the study, which launched two years ago, was to support development of more sensitive ways to assess canine vision — something that has been sorely lacking in veterinary medicine.

Freya Mowat

“The method we currently use to assess vision in dogs is a very low bar. In humans, it would be equivalent to saying yes or no if a person was blind,” says Mowat. “We need more sensitive ways to assess vision in dogs, using a dog eye chart equivalent. We speculate that videos have the potential for sustaining a dog’s attention long enough to assess visual function, but we didn’t know what type of content is most engaging and appealing to dogs.”

Published recently in the journal Applied Animal Behaviour Science, the study found that dogs are most engaged when watching videos that feature other animals. Content featuring other dogs was the most popular. But if a National Geographic documentary about canine evolution seems too highbrow for your four-legged friend, Scooby Doo might be a perfectly acceptable option as well.

To better understand the type of content dogs might be most attracted to on screen, Mowat created a web-based questionnaire for dog owners around the globe to report the TV-watching habits of their canine companions.

Participants responded to questions about the types of screens in their homes, how their dogs interacted with screens, the kinds of content their dogs interacted with the most, as well as information about their dog’s age, sex, breed and where they live. They also provided descriptions of their dogs’ behavior when watching videos. Most commonly, dog owners described their pets’ behavior as active — including running, jumping, tracking action on screen and vocalizing — compared with passive behaviors like lying down or sitting. Dog owners also had the option to show their dog(s) four short videos featuring subjects of possible interest, including a panther, a dog, a bird and traffic moving along a road. They were then asked to rate their dog’s interest in each video and how closely the dog tracked the moving objects on the screen.

In this video, a dog watches scenes of another dog going for a walk.

Mowat received 1,600 responses from dog owners across the world, including from the United States, Canada, the United Kingdom, the European Union and Australasia. Of those respondents, 1,246 ultimately completed the study. The following are some of the most interesting highlights:

• Age and vision were related to how much a dog interacted with a screen.
• Sporting and herding dog breeds appear to watch all content more than other breeds.
• Video content featuring animals was the most popular, with other dogs being by far the most engaging subjects to watch.
• Humans do not appear to be very appealing for dogs to watch, ranking ninth out of 17 predetermined categories.
• Cartoons were engaging for more than 10% of dogs.
• Movement on screens was a strong motivator for screen attention.

Mowat says she plans to build on the results of this study. Future research will focus on the development and optimization of video-based methods that can assess changes in visual attention as dogs age as well as answer questions that could help our four-legged friends age as gracefully as possible.

“We know that poor vision negatively impacts quality of life in older people, but the effect of aging and vision changes in dogs is largely unknown because we can’t accurately assess it,” she says. “Like people, dogs are living longer, and we want to make sure we support a healthier life for them as well.”

Another goal for Mowat is to compare how a dogs’ vision ages compared with the human or humans they share a home with.

“Dogs have a much shorter lifespan than their owner, of course, and if there are emerging environmental or lifestyle factors that influence visual aging, it might well show up in our dogs decades before it shows up in us,” she explains. “Our dogs could be our sentinels — the canine in the proverbial coal mine.”

This study was supported in part by an NIH career development grant to Mowat (K08EY028628), a Companion Animal Fund Grant from the UW–Madison School of Veterinary Medicine, a grant from Research to Prevent Blindness, Inc. to the UW–Madison Department of Ophthalmology and Visual Sciences and a core grant for Vision Research from the NIH to UW–Madison (P30 EY016665).

A container of syringes with pre-measured shot doses of the Pfizer-BioNTech vaccine is pictured. Photo: Jeff Miller

The effectiveness of mRNA vaccines in reducing disease severity and hospitalization from COVID-19 is well established. Now, new research from the University of Wisconsin School of Veterinary Medicine advances our understanding of how these vaccines protect the lungs following breakthrough infections from emerging variants of SARS-CoV-2, the virus that causes COVID-19.

Published on Oct. 5 in the journal JCI Insight, the study is the first to directly demonstrate the role of memory CD8 T cells in mRNA vaccine-induced immunity to COVID-19. Memory CD8 T cells are a specialized type of white blood cell that rapidly respond when re-exposure to a pathogen occurs.

They are often referred to as “trained assassins” because they control viral infections by targeting and then destroying virally infected cells. This study, conducted in mice, shows that memory CD8 T cells were necessary and sufficient in controlling SARS-CoV-2, independent of antibodies. Researchers demonstrated this by showing how the protection afforded by mRNA vaccines was lost in mice when memory T cells were depleted prior to SARS-CoV-2 infection.

Scientists widely accept that CD8 T cells provide a more robust form of protection because the viral fragment they target to kill infected cells does not change considerably with each new viral variant. Antibodies on the other hand, typically lose their ability to prevent infection because the part of the virus they target changes with each new mutation.

Marulasiddappa Suresh

Marulasiddappa Suresh, professor of immunology in the School of Veterinary Medicine Department of Pathobiological Sciences, says this study sheds new light on the protective mechanisms mRNA vaccines use to lessen severe disease following breakthrough infections. It also raises important new questions about the role of memory T cells in limiting the spread of the virus, the frequency with which we get vaccinated and the most effective methods for vaccine delivery.

“The key finding of our research shows that memory T cells play an essential role in mediating SARS-CoV-2 viral control in lungs, independent of antibodies,” says Suresh, who was also the study’s principal investigator. “We hope this new understanding of vaccine-induced immunity will inform the development of new vaccines and treatment strategies that more effectively combat the emergence of global variants and limit the impact they’ll have on our health in the future.”

While previous studies have documented a strong correlation between vaccine-induced T cells and more positive outcomes following infection with SARS-CoV-2, the ability to study these protective mechanisms in detail is not possible in humans. As a result, researchers administered various doses of the Pfizer BioNTech COVID-19 mRNA vaccine to a specialized mouse model in order to study the defining characteristics of T cell responses induced by the vaccine. Their results showed the T cell response to mRNA vaccine in the peripheral blood is largely similar between mice and humans. They also found that T cells actively sought out the virus in the respiratory tract — airways, lung vasculature, and mediastinal lymph nodes — to effectively reduce the burden of SARS-CoV-2 in the lungs.

Other key findings show that intramuscular immunization produced unexpectedly high frequencies and numbers of memory T cells in the airways of the respiratory tract — the main portal of entry for SARS-CoV-2. According to Suresh, future research on this topic will need to assess the biological significance of nasal and airway resident memory T cells in protection against emerging variants of SARS-CoV-2 and whether individuals who recover from breakthrough SARS-CoV-2 infections will require further vaccinations.

“It’s still unclear if the combination of vaccine-induced immunity and infection-induced immunity is sufficient to provide broad mutation-resistant immunity to future SARS-CoV-2 variants,” he says.

Other members of the research team from the UW School of Veterinary Medicine include Brock Kingstad-Bakke, Thomas Cleven, Hailey Bussan, Hongtae Park, Peter Halfmann and Yoshihiro Kawaoka from the Department of Pathobiological Sciences; and Jay Mishra and Sathish Kumar from the Department of Comparative Biosciences. Other important contributors include researchers from the University of North Carolina, Chapel Hill; University of Tokyo; and Japan’s National Center for Global Health and Medicine Research Institute.

This study was supported by PHS grant U01 AI124299, R21 AI149793-01A1, R21 AI173757-01A1.

Red colobus monkeys in Kibale National Park, Uganda. The species are natural hosts of arteriviruses related to SHFV. Tony Goldberg

In a world still reeling from COVID-19, infectious disease researchers are eager to head off the next pandemic before it has the chance to spill over from animals to humans. But the scientific reality of pandemic prevention isn’t straightforward, and researchers have generally avoided making specific predictions about the potential of individual viruses to cause global disease.

Sometimes, though, a signal is so compelling it can’t be ignored. One such signal has prompted a group of scientists to sound the alarm about an obscure virus in wild African primates — despite the fact that neither the virus nor any of its close relatives have ever been documented in humans.

“It’s a pretty controversial prediction,” concedes Tony Goldberg, a professor of pathobiological sciences at the University of Wisconsin School of Veterinary Medicine.

Goldberg is part of the group warning that simian hemorrhagic fever virus (SHFV) and its family of simian arteriviruses could pose a significant health risk to humanity should the right conditions allow it to leap from wild primates to people. The group has demonstrated the virus’s ability to infect human cells and deftly evade the human immune system’s typical responses. They have recently published their findings in the journal Cell.

The researchers say there is no known risk to people now, and there is no guarantee the virus will make the jump from wild primates. But Goldberg and his colleagues say it’s important to understand these viruses and the risks they could pose.

Goldberg and his collaborators on other campuses carried out sophisticated laboratory analyses that inform the group’s assertions. Their most recent lab work stems from a decades-long effort by Goldberg and colleagues to hunt down and describe potentially dangerous viruses lurking in wild places. In fact, it was Goldberg’s field work in the forests of Uganda that first identified wild strains of simian arteriviruses — strains used to understand the virus’s infectious potential in this latest research.

“About 12 years ago, I decided to do some virus hunting on monkeys just to see what they had, because it was all the rage,” says Goldberg. “There’s this idea that monkeys are important reservoirs for future pandemic viruses.”

That line of thinking is informed in part by the world’s experience with HIV, the human immunodeficiency virus, a pandemic that has killed millions since the virus was first identified in the 1980s. HIV is believed to have made the leap from wild primates to humans sometime in the early 20th century and spread slowly and quietly for decades until the right conditions allowed its transmission to explode with devastating consequences for global health.

In his hunt for other potentially dangerous viruses, Goldberg took blood samples from wild primates in Uganda’s Kibale National Park. Back in Madison, Goldberg analyzed the samples with David O’Connor, a professor of pathology and laboratory medicine at the UW School of Medicine and Public Health (SMPH), and with Tom Friedrich, a professor of pathobiological sciences at the UW School of Veterinary Medicine. Together, the researchers applied early technologies in deep genome sequencing to look for viruses and identified multiple wild relatives of SHFV.

Fieldwork in Kibale National Park, Uganda. Pictured are collaborating veterinarian Dr. David Hyeroba (left) and Kibale EcoHealth Project field assistant Patrick Katuramu (right). Tony Goldberg

This initial finding was important for several reasons, first and foremost being that it was the first time any relative of SHFV had been found in the wild. The virus had been implicated previously in mass deaths of captive macaques stricken with an Ebola-like hemorrhagic fever. Scientists believed the macaques were exposed to the virus from wild primates they encountered in captivity, and now Goldberg, O’Connor and Friedrich were able to provide evidence of SHFV’s wild origins.

“That launched a decade of work with Dave, Tom and others looking at different variants of the virus,” says Goldberg. These investigations helped train a cohort of UW–Madison graduate students and post-doctoral scholars, such as Adam Bailey, then a graduate student and now a professor at SMPH.

A color-enhanced electron micrograph of SHFV growing in cell culture. NIAID Integrated Research Facility at Fort Detrick

More than a decade later, the group studying SHFV’s pandemic potential has evolved. The latest research, led by scientists at University of Colorado Boulder, The Ohio State University and the National Institutes for Health, provides evidence that SHFV is not only a deadly threat to macaques but that it could cause similar disease in humans if the virus were able to make that inter-species jump.

The findings amount to a bit of a “told you so” moment for Goldberg, who, with O’Connor, previously tried unsuccessfully to convince NIH to fund research investigating the possibility of SHFV infecting humans. He credited the “very fine, very careful” laboratory work of his colleagues in Colorado and Ohio with moving the research so far ahead.

“This is somewhat of a vindication” he says.

Read more about the recent study from the CU Boulder.

Now, in a new study, researchers at the University of Wisconsin School of Veterinary Medicine describe another way the bacterium can cause harm: by undermining the body’s ability to heal from those infections.

The findings may point the way toward improving treatment of infections with S. aureus, more commonly called a staph infection.

Wilmara Salgado-Pabón

The S. aureus bacteria produce small toxins, called superantigens, that bind to white blood cells and over-activate the immune system, which can cause complications for the circulatory system. The study in rabbits, published recently in Science Advances, found that a superantigen called SEC (superantigen staphylococcal enterotoxin C) prevents injured blood vessels from healing. It also stops the formation of new branching blood vessels crucial to the wound repair process.

“The role of many immune system molecules is to make the vessels around the infection more permeable, so they can enter and heal the infection,” explains senior author Wilmara Salgado-Pabón, professor of pathobiological sciences. “But when superantigens hyperactivate the immune system, your blood vessels can become leaky, leading to low blood pressure and organ dysfunction.”

When an area of the body has suffered injury, it will form tiny branching blood vessels called capillaries, which send nutrients and oxygen to the damaged area. Using what’s called the aortic root model, researchers sliced small sections of a rabbit’s aortic artery to imitate an injury. These ring slices were unable to form new capillaries in the presence of SEC, hindering the vascular system from healing the injury.

The model works well, says Salgado-Pabón, “because it allows us to test capillary formation — which can be complex — in a laboratory environment, with all of the elements you would expect in the body.”

Infective endocarditis disproportionately affects Black and Indigenous populations, as well as people predisposed to infection — such as the elderly, people with diabetes and people who smoke.

The condition is responsible for high rates of in-hospital mortality, as it progresses very quickly and can go on to cause complications in other organs throughout the body, Salgado-Pabón says.

Over the last 50 years, treatment for infective endocarditis has remained largely unchanged, currently consisting of a six-week course of antibiotics or heart surgery to clear the infection. The new findings offer potential for developing new and better approaches.

“You could not only neutralize the toxins’ vascular effects, but you could possibly treat patients to improve their vascular health,” says Salgado-Pabón, whose work is supported by the National Institutes of Health. “By strengthening a patient’s vascular health, you could proactively prevent the complications that lead to fatality.”

Now that the lab has identified this new biological function, it is working to define the structures and molecules that are critical to the process, including identifying the molecules SEC interacts with and defining the cellular receptors that react to the toxin’s presence.

This work was supported by NIH grants R01AI34692-01 (to W.S.-P.), R01AI136500 (to J.E.G.), 5T32AI007511-23 (to P.M.T.), and T32GM008365 (to K.J.K.).

A rabbit listens between nibbles in the Grady Kettle Hole Forest at the UW–Madison Arboretum. Photo: Bryce Richter

Researchers and clinicians are sounding the alarm as the fatal rabbit hemorrhagic disease, RHDV2, spreads across the U.S. In response, the UW Veterinary Care Special Species Health Service at the University of Wisconsin School of Veterinary Medicine has begun offering an emergency-authorized vaccine against the disease for rabbits.

The clinic is one of about a dozen animal hospitals in the state to offer the vaccine and part of a growing effort nationally to encourage rabbit owners to seek vaccination. UW Veterinary Care offers the RHDV2 vaccine on Fridays every three weeks through the Special Species Health Service. Any rabbit patients in Wisconsin are welcome; owners do not need to be previously established clients with UW Veterinary Care to make an appointment.

RHDV2 is a highly contagious foreign animal disease that likely originated in Europe. It affects both domestic and wild rabbits but is not spreadable to other species or humans.

The first strain of rabbit hemorrhagic disease was discovered around 2010. Since then, it has traveled to North America and mutated into the form of the virus that is now wreaking havoc on U.S. wild rabbit populations, primarily in the West. The U.S. Department of Agriculture expedited the vaccine distribution process, granting emergency authorization in September 2021 to tackle the problem and limit the disease’s spread to commercially raised and domestic rabbits.

Among the most popular pets in America, rabbits rank third behind dogs and cats, with an estimated 3 million rabbits kept as pets in U.S. homes.

Kurt Sladky, a veterinarian and clinical professor of zoological medicine and special species health at the UW School of Veterinary Medicine, believes the virus is likely in Wisconsin despite an absence of detected cases.

“Some wild rabbits, if found dead and suspected of disease, are submitted to laboratories equipped to make the diagnosis, such as the National Wildlife Health Center here in Madison,” Sladky says. “But there’s no easy way to find and track how many have died in the wild.”

Sladky describes the disease as devastating. Once rabbits have contracted the virus, they typically bleed to death. With the currently circulating strains of the virus, veterinarians and public health officials expect the mortality rate to be extremely high — killing between 70 to 100 percent of infected rabbits.

The virus spreads easily through contact with body secretions such as saliva, urine and blood. It can live up to a month on surfaces like clothing or blades of grass, increasing its transmissibility.

“Your rabbit could become infected through urine, feces, blood … even a fly could land on a carcass with the virus and transmit it to another rabbit if the fly’s feet make direct contact with the nose of another rabbit,” Sladky says. “It’s so easily transmissible rabbit to rabbit.”

Pet rabbits are becoming vulnerable, Sladky warns, because of the virus’s numerous outbreaks and staying power. The disease’s global spread is believed to have occurred through routes like rabbit shows and meat production chains. For this reason, UW Veterinary Care’s Special Species clinicians requested access to the vaccine as quickly as possible for their patients. In 2021, the hospital saw nearly 800 rabbit patient visits.

The USDA and Wisconsin Department of Agriculture, Trade and Consumer Protectoin collaborated to authorize a two-dose series of shots produced by Medgene Labs, a South Dakota company. The vaccine is similar to one successfully developed in Europe. Studies show the U.S.-produced vaccine is highly effective. It consists of an initial dose, a booster three to four weeks later and a yearly booster.

In addition to the vaccine, Sladky recommends other steps to protect pet rabbits. Though the weather is warming and outdoor exercise might be ideal, pet rabbits should refrain from going outside — or at least until they are fully protected by the RHDV2 vaccine. In addition, rabbit owners should purchase hay, a core component of a rabbit’s diet, from known reputable sources. Ultimately, preventing access to other rabbits, especially wild rabbits, remains key.

“We’re trying to educate clients that an important infectious disease of rabbits is spreading from state to state,” Sladky says. “You should think about the ways your pet rabbit could become exposed and the potential consequences.”

For more information on the rabbit vaccine clinics, call UW Veterinary Care at 608-263-7600.

These days, programming created specifically for dogs is more frequently popping up on our screens. YouTube offers a nearly endless supply of dog-centered videos, and there’s a growing number of television and streaming channels promising 24/7 content to keep pups entertained or even alleviate stress or separation anxiety while owners are away.

But very little is actually understood about how dogs engage with this kind of programming, and what kind of videos most appeal to them.

Now, a new citizen-science study led by a University of Wisconsin–Madison professor is asking dog owners to help shed some light on these questions. It’s no trivial business, as the results could lay the groundwork for developing better ways of assessing vision in dogs.

Freya Mowat

“The overarching goal in this study is to figure out what dogs like to watch on television,” says Freya Mowat, a veterinary clinician-scientist. “This is interesting from a dog behavior standpoint, but as dog vision researchers, we also want to develop engaging methods to test dog vision in either the home or clinic, which we currently just do not have.”

Mowat, an assistant professor at the UW School of Veterinary Medicine’s Department of Surgical Sciences and the School of Medicine and Public Health’s Department of Ophthalmology and Visual Sciences, says previous efforts to develop an eye test for dogs have resulted in more than a few “epic fails.” Trying to adapt human vision tests for dogs has proved challenging, at best, or required too much training to be viable.

But Mowat believes videos could potentially be the key to holding a dog’s attention long enough to gather and assess critical information about visual function. The trick is determining the type of content that’s most engaging and appealing to dogs.

To better understand what dogs might be most attracted to on screen, Mowat is seeking individuals from around the globe, and their canine companions, to participate in a “Dog TV” survey. The unique questionnaire asks people to provide information on their dog’s screen-viewing habits, as well as information about the dog’s age, sex, breed, and where they live.

Participants can also take the optional step of showing their pooch four short videos of subjects potentially of interest to dogs, such as objects and other animals. People will then rate their dog’s interest in each video and how closely the dog tracked the moving objects in the videos.

“We intend for this to be a fun activity for both dogs and their people,” Mowat says. “And we’d really love to get thousands of responses from individuals across the world, so we can better understand if dogs in Wisconsin like the same kind of videos as dogs in New York or Brazil or any other location.”

Previous efforts to develop an eye test for dogs have resulted in more than a few epic fails. Trying to adapt human vision tests for dogs has proved challenging.

Ultimately, Mowat says the study could also help answer a question of interest to all dog owners: How do we help our four-legged friends age gracefully?

“As they get older, do dogs need things like brighter lighting in their environment to prevent them from tripping down the stairs in the middle of the night, or other visual cues to help them locate things? These are questions we genuinely don’t know the answers to,” Mowat says. “We do know that canine retinal function does decline with age and can decline quite significantly. So it’s more than likely that visual perception does change, but what that actually means from a lifestyle standpoint is the missing piece of the puzzle.”

A future goal, says Mowat, is to compare how a dog’s vision ages compared with the human or humans they share a home with.

“After all, a dog has a much shorter lifespan than their owner, and so if there are emerging environmental or lifestyle factors that influence visual aging, it might well show up in our dogs decades before it shows up in us,” Mowat explains. “Our dogs could be our sentinels — the canine in the proverbial coal mine.”

Ready to take part and help advance vision research for our canine companions? Click here to answer the questionnaire, which will take approximately 10 to 20 minutes. There is no anticipated risk to study participants or their dogs.

The findings offer guidance to physicians to help mitigate risk to children of a significant number of expectant parents. By the third trimester, sleep apnea appears in about 15 percent of normal pregnancies and 60 percent of high-risk pregnancies.

Several studies out of the school have shown, using a rat model, that sleep apnea during pregnancy may have a variety of detrimental effects —from high blood pressure to inflammation in the brain to altering the microbiome of the intestinal tract — on male offspring. Researchers studied both male and female offspring, but found the effects most pronounced in males, with many problems not emerging until adulthood. The reason for this remains under investigation.

Jyoti Watters

Most recently, a study published in the journal PLOS Biology and led by Michael Cahill, Jyoti Watters and Tracy Baker, professors in the Department of Comparative Biosciences, shed light on the cognitive and behavioral impacts sleep apnea in pregnancy may have on offspring. The researchers exposed pregnant rats in the latter half of their pregnancy to brief, intermittent periods of low oxygen that mimic the low oxygen levels experienced in sleep apnea (which does not occur naturally in rats).

Male offspring of these rats were more likely to exhibit behavioral changes resembling autism than female offspring or offspring whose mothers were not exposed to low oxygen levels. These behavioral changes, including abnormal vocalization patterns, impaired memory, reduced social interest and increased repetitive behaviors were often first observed shortly after birth, and continued into adulthood.

“Our data provide clear evidence that maternal sleep apnea may be an important risk factor for the development of neurodevelopmental disorders, particularly in male offspring,” Cahill says in a PLOS Biology press release.

Michael Cahill

In addition to these behavioral changes, the study found physical abnormalities in the brain cells of offspring from mothers in which they mimicked sleep apnea.

The dendritic spines, a part of the neuron responsible for receiving and acting on signals from other neurons, were found in a higher density in the brain’s cortex and with atypical size and structure compared to offspring born from the control rats. These changes were observed in both male and female offspring; however, the effect was significantly worse in males. An abnormal increase in the density of dendritic spines in this region of the brain has also been identified in autism in humans.

Though it remains unclear how exposing pregnant rats to the recurrent low oxygen levels that occur in sleep apnea caused these changes, during normal brain development the number of dendritic spines is “pruned” or reduced — a process investigators think is lacking in the offspring of the experimental rats.

Tracy Baker

Watters and Baker are addressing other wide-ranging impacts of sleep apnea in pregnancy and why these seem only to affect males.

“There are several areas that we have been looking at, one of the major things being the offspring’s respiratory function,” Watters says.

If your parents have sleep apnea you are more likely to develop it as well. However, no specific genetic mutation has been identified. In a study recently submitted for publication, Baker and Watters showed that mothers with sleep apnea during pregnancy may be able to pass the condition on to their offspring due simply to the in-utero experience of intermittent low oxygen.

“It was very interesting to us that we could link maternal intermittent low oxygen to an increased risk for sleep apnea development in adult male offspring, because this is something that has not been conceived of before,” Watters says.

Sathish Kumar

A study led by colleague Sathish Kumar, a UW–Madison professor of comparative biosciences, found that maternal intermittent low oxygen also increases the risk for developing high blood pressure in adult males.

“That’s another aspect our work is trying to address: how and why does this constellation of deficits occur almost exclusively in the male offspring?” Baker says.

While researchers continue to investigate, Baker suggests that maternal sleep apnea’s effect on the developing offspring’s brain could be an important root cause. Because the brain controls every organ system in the body, the inflammatory response within the offspring’s brain can have a cascading effect throughout the body.

A worldwide rise in sleep apnea, in part due to an increase in obesity, makes it especially important to understand the risks of maternal sleep apnea.

“A main goal of our research is to raise awareness in physicians who take care of pregnant people,” Watters says. “They should be asking their patients questions about their sleep to determine whether they should be screened for sleep apnea and encouraging them to adhere to the treatment.”

Though treatment for sleep apnea is readily available (most commonly in the form of a continuous positive airway pressure, or CPAP, machine), up to 50% of those diagnosed go untreated in part due to discomfort and feelings of claustrophobia while wearing the CPAP mask. And many patients go undiagnosed altogether.

Baker and Watters are collaborating with an obstetrician-gynecologist in Texas to share their research and determine if findings in the rat model apply to humans.

In July, Baker was awarded a patent for a potential therapy to treat sleep apnea in humans, a positive step in effectively treating the disorder. Baker shares the invention with colleagues Gordon Mitchell, professor of neuroscience at the University of Florida, and Daryl Fields, a University of Pittsburgh neurosurgeon who earned his doctorate in neuroscience at UW–Madison.

Like many hibernators, thirteen-lined ground squirrels retain muscle tone and healthy gut microbiomes through hibernation even though they aren’t eating or moving around. Their success at rest may help humans make long space voyages. Photo by Rob Streiffer

To get through a long winter without food, hibernating animals — like the 13-lined ground squirrel — can slow their metabolism by as much as 99 percent, but they still need important nutrients like proteins to maintain muscles while they hibernate. A new study from the University of Wisconsin–Madison shows that hibernating ground squirrels get help from microbes in their guts.

The discovery could help people with muscle-wasting disorders and even astronauts on extended space voyages.

“The longer any animal doesn’t exercise, bones and muscles start to atrophy and lose mass and function,” says Hannah Carey, an emeritus professor in the UW–Madison School of Veterinary Medicine and co-author of the new study, published today (Jan. 27) in the journal Science. “Without any dietary protein coming in, hibernators need another way to get what their muscles need.”

One source of nitrogen, a vital building block for amino acids and proteins, accumulates in the bodies of all animals (including humans) as urea, a component of urine. The researchers knew that urea that moved into the squirrels’ digestive tract could be broken down by some gut microbes, which also need nitrogen for their own proteins. But the researchers wanted to see if some of that urea nitrogen freed up by the microbes was also being incorporated into the squirrels’ bodies.

They injected urea made with trackable isotopes of carbon and nitrogen into the blood of squirrels at three stages — during the active days of summer, early in winter hibernation and late in winter. Some of the squirrels had also been treated with antibiotics to kill off the majority of the microbes in their intestines. As predicted, isotope-containing nitrogen was released by some of the gut microbes that degraded the injected urea.

Thirteen-lined ground squirrels curled up for seasonal hibernation can slow their metabolic rates to as little as 1 percent of their waking activity. Courtesy of Rob Streiffer

“We followed that nitrogen to (the) livers (of the squirrels), primarily — where it is used to make many proteins — and some to muscles,” says study co-investigator Fariba Assadi-Porter, an UW–Madison emeritus biochemist who specializes in tracking the isotopes. She is also a scientist in Integrative Biology and the university’s Nuclear Magnetic Resonance Facility. “We believe we’re seeing the isotope-labeled nitrogen molecules go from the host to the microbiome, then converted to usable molecules by the microbes before coming back to the host again, essentially being ‘recycled’ in the hibernating animal.”

The researchers observed two differences that support this microbial path. The squirrels whose gut microbes were largely depleted by antibiotics had far less of the trackable nitrogen in their liver and muscles. And when the researchers sequenced the genomes of microbes found in the squirrels’ guts, they found that as winter hibernation dragged on there was an increase in the presence of genes related to production of an enzyme called urease.

“Urease is not made by animals. Only microbes that express urease are able to split the urea molecule and release its nitrogen,” says Carey, whose work is supported by the National Science Foundation. “As long as the right microbes are present, it’s a transaction between them and the host — each get some of the nitrogen released to tide them over until hibernation ends.”

Describing the keys to survival over the duration of hibernation could help people on low-nitrogen diets or with disorders that cause muscles to atrophy. It could also make it possible for humans to make lengthy trips to distant planets.

Putting space travelers into a hibernation-like state means they wouldn’t need to take as much food, water and oxygen, and would produce less waste and carbon dioxide, saving vast amounts of weight and fuel.

“This process could theoretically reduce rates of muscle loss in space, where microgravity exposure invariably leads to muscle atrophy,” says Matthew Regan, a study co-author and former UW–Madison postdoctoral researcher who is now a professor of animal physiology at the University of Montreal. “And because characteristics of hibernation beyond this gut microbe-dependent process confer protection against other hazards of space flight such as ionizing radiation, it is theoretically possible that, if translated to humans, hibernation-like states could solve numerous challenges of human spaceflight simultaneously.”

This research was funded by grants from the National Science Foundation (IOS-1558044 and DGE-1747503), the National Institutes of Health (P41GM136463, P41GM103399, P41RR002301 and T32GM008349) and the Natural Sciences and Engineering Research Council of Canada.