The potential for new zoonotic diseases worldwide is huge – and continues to grow. In Switzerland too, there are dangerous germs that can spread from animals to humans. Researchers at UZH are tracking them down.
Text: Stefan Stöcklin
Translation: Philip Isler
The idea is a fairly obvious one. And yet, Cornel Fraefel and his team at the Institute of Virology at UZH were the first to actually try it in Switzerland: They analyzed the viruses carried by bats. The winged mammals are known for their robust immune systems and for living together in close quarters, which makes it easy for viruses to circulate among them. Bat colonies can thus be reservoirs of a number of potential pathogens that could be harmful to humans. The study, conceived by Cornel Fraefel and Jakub Kubacki, was conducted by PhD candidate Isabelle Hardmeier. It took several years to complete and was a great success. The researchers collected around 7,000 fecal and tissue samples from 18 bat species in Switzerland, and found DNA sequences of 39 different families of viruses, including some notorious for causing disease.
Bats with coronaviruses
Finding a betacoronavirus in the stool sample of a parti-colored bat (Vespertilio murinus) gave the scientists particular cause for concern. Genetic analyses revealed that it was closely related to a type of coronavirus that was responsible for an outbreak of MERS (Middle East Respiratory Syndrome) in the Middle East in 2012 that claimed hundreds of lives. “Our study demonstrates how important it is to survey bats in Switzerland on a regular basis,” says Cornel Fraefel, referring to the great diversity of viruses found in the study. Some of them have yet to be classified.
The study’s preliminary findings emerged at the height of the first wave of the Covid-19 pandemic in the spring of 2020, garnering widespread attention. Now published, the paper confirms what researchers have been saying time and again for years – the diversity of unknown viruses and the risk of new pathogens spilling over from animals to humans, referred to as zoonotic diseases or zoonoses, is huge. A new pandemic may be just around the corner, so to speak. This doesn’t only concern far-flung exotic places, but could happen right here in Switzerland. In a recent study, experts estimate that there are around 1.7 million unknown viruses in mammals and bird species alone. Of these, some 700,000 can potentially infect humans, the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) warns in a study. And this number doesn’t even include the thousands of bacteria and parasites that pose a risk to people. The most important reservoirs of potential viral pathogens are bats, rodents, primates, water birds and livestock such as pigs or poultry.
Infecting human cells
“Bats have a number of distinct biological traits that make them ideal reservoirs for viruses and spreading them,” says Cornel Fraefel. Such traits include their robust immune systems and their lifestyles. Bats are fairly long-lived creatures that can live up to 40 years, they can cover hundreds of kilometers, and often live together in caves in huge colonies of up to several million. These crowded conditions and their mobility are ideal for passing viruses to one another, and they can also pass them on to people, either directly over through an alternate host.
For a virus to change hosts and pass to a human, it first has to acquire new properties that allow it to infect human cells. This is precisely what happened in the SARS outbreak of 2003, when a coronavirus spread to humans via an alternate host. The current coronavirus very likely also originated in bats, but this hasn’t yet been proven. A close relative of the novel coronavirus SARS-CoV-2 by the name of RaTG13 was tracked down in a population of horseshoe bats in Southern China, though whether the current pandemic can be traced back to this virus or another precursor is currently unclear.
Climate change, wildlife trade
According to the IPBES study, there are on average five new germs every year that can make the initial jump from animals to humans. However, most of these are unable to adapt to the new host. But when the pathogen does succeed in establishing itself and reproduces, it can result in an epidemic, which at worst can turn into a global pandemic. Experts believe such outbreaks, both major and minor, are occurring more and more frequently. Examples include the H5N1 bird flu in Hong Kong in 1997, the Nipah virus in Malaysia in 1998, SARS-CoV-1 in Guangdong in 2002, MERS in Saudi Arabia in 2012, the Ebola virus in Guinea in 2016, and SARS-CoV-2 in Wuhan in 2019.
Since every outbreak can be traced back to physical contact between an animal and a human, the increasing frequency is explained by the fact that such interactions have become more and more common, especially contact with wildlife. This is due to slash-and-burn farming in the jungle and expanding agriculture in general, wildlife trade and increasing global mobility. In addition, climate change is making it easier for pathogens to spread.
For example, Asian tiger mosquitoes (Aedes albopictus) can now also be found in Switzerland. Originally found in Southeast Asia, the insect was first seen in Switzerland in Ticino in 2003, where it has since become established, with regular sightings north of the Alps too. “The tiger mosquito is a perfect example of the effects of climate change,” says Cornel Fraefel. Its spread is cause for concern, since tiger mosquitoes can carry harmful zoonotic diseases such as dengue fever, yellow fever or the Zika virus. Fraefel and his team recently analyzed more than 500 tiger mosquitoes from the Ticino region – fortunately, so far they haven’t found any dangerous viruses. And yet, the virus expert believes it is only a matter of time before the first transmission of Zika or dengue from local tiger mosquitoes occurs in Switzerland. “We have to expect these zoonoses to take hold here,” he predicts.
When viruses have sex
The world of microbes and their hosts can be described as a constant struggle between adaptation and defense. For a bacterium or a virus, the most promising strategy is to be able to attack as many host animals as possible and cross over to new species. Random mutations enable the microorganisms to find new victims, while the hosts’ immune system fends off as many of the attackers as possible. If the virus encounters a related virus, what happens could be described as the viruses having sex. They exchange genetic material, and this allows them to evade the immune system’s defenses for a while. Influenza viruses are particularly skilled at this kind of genetic change.
It gets especially dangerous when influenza A viruses from different species of host animals mix their genetic material. Each of the influenza strains circulating in pigs, birds and humans are different. Reassorting these variants could result in pandemic strains that are very likely to overwhelm the human immune system. In 1997, a new bird flu pandemic was narrowly avoided in Hong Kong by killing millions of chickens. The 1918 flu pandemic, in contrast, swept across the whole planet in several waves, claiming between 20 and 50 million (mostly young) lives. In comparison, as of the fall of 2021, some 4.5 million people have died of Covid-19.
New flu pathogen
Due to their genetic features, flu viruses are considered a constant pandemic threat, and as such they are also the subject of research at UZH. Alarm bells began to ring when US scientists discovered a previously unknown influenza A virus in bats a few years ago. To the researchers' great surprise, the virus, found in a little yellow-shouldered bat (Sturnira lilium), used a different pathway to infect cells than other known strains of influenza A viruses. It is part of a new group of viruses, and transmission to humans could have catastrophic consequences.
Silke Stertz from the Institute of Medical Virology at UZH heads up a group that is investigating the new virus’s infection process at a molecular level. The molecular biologist not only recently discovered a new entry receptor used by the virus, but was also able to detect it in human and other cells, as well as infect mice cells with the bat virus. “The virus has zoonotic potential and is a possible threat to humans,” concludes Silke Stertz. It’s difficult to estimate how great this potential is, says the researcher, but the virulence of other influenza A viruses is reason for caution.
The new flu virus shines a light on the multitude of constantly changing viruses and bacteria in the animal kingdom. Just recently, researchers may have discovered a virus in Guatemala that is only a few mutations removed from being able to infect humans. To reduce the risk of new zoonotic diseases for humans, expert such as Silke Stertz and Cornel Fraefel are backing additional monitoring programs for wildlife and farm animals known to harbor zoonotic pathogens. Here, One Health means not allowing new diseases to develop in the first place. Admittedly, obtaining samples from local water birds or chickens is much easier than getting them from bats in remote caves or from jungle wildlife. It remains to be seen just how feasible such plans to closely monitor animals and detect new zoonotic diseases actually is. If past experience is anything to go by, it’s very likely that the microbes are already one step ahead.
Animal Pathogens Crossing Over
Most human diseases originated in the animal kingdom. Many crossed over from animals as a result of major societal changes, for example during the Neolithic Revolution. When hunter-gatherers began to farm and domesticate animals and settle in villages some 12,000 years ago in Mesopotamia, they started living in close proximity to their animals. Germs soon jumped over from herds to humans and caused diseases such as diphtheria, influenza, measles and pox. Over time, the germs adapted to their new hosts so well that they began to spread exclusively among humans.
One of the most dramatic zoonotic diseases is the bubonic plague, which is caused by bacteria called Yersinia pestis. Since the 14th century, recurring plague epidemics have cost millions of lives. The tuberculosis epidemic in the 18th century also has zoonotic origins and is linked to industrialization and overpopulation in Western Europe. The AIDS-causing HI virus is an example of how increasing mobility in the 20th century accelerated the spread of a pathogen that had for decades only affected very few people in tropical central Africa. Genetic analyses of blood samples taken from hospital patients in 1960s Congo suggest that HIV came from a simian retrovirus, which must have made the leap to humans at the beginning of the last century.