SPECTRUM. Hunting Invisible Viruses: Threats to Humans Lurking in the Animal Kingdom

Viruses are the most abundant biological entities on Earth. Scientists estimate that more than 99% of them remain undescribed. Some of these invisible pathogens live in wild animals, and often neither cause serious illness nor pose a major threat to humans. Occasionally, however, viruses cross the species barrier and give rise to new diseases.

One such example is the Nipah virus outbreak in Malaysia. The virus passed from fruit bats to pigs and subsequently infected humans, claiming more than 100 lives. 

To understand how such viruses emerge and evolve, Dr Milda Norkienė, a researcher at the Life Sciences Center of Vilnius University, and her colleagues are studying the diversity and evolution of polyomaviruses found in animals, as well as their potential threat to human health.

Viruses that live among us

Viruses are often associated with disease, but most of them are not actually dangerous to humans.

‘There is an enormous diversity of viruses in nature, and we encounter them constantly without even noticing. For example, when we eat plants, we also ingest plant viruses, while the bacteria living in our gut are infected by viruses of their own – bacteriophages. Yet this doesn’t mean that all of them are dangerous to us. Most are highly ‘selective’ and can reproduce only in a particular host,’ said VU researcher Dr Norkienė. 

The same is true of polyomaviruses. Many of us were probably infected with at least one of them in childhood without ever realising it, as the infection usually causes no symptoms. These viruses can remain in the body for many years and become active only under exceptional circumstances.

Although the polyomavirus family is relatively small, research into these viruses has profoundly influenced biology and medicine. By analysing how they take over cellular machinery and force cells to copy viral genetic material, researchers have gained a better understanding of cell division, DNA replication, and even the development of certain tumours. This is why the search for new polyomaviruses continues to this day.

‘Polyomaviruses are found in a wide range of animals, from mammals to fish. Although few people have heard of them, scientists have already identified 16 polyomavirus species associated with humans, most of them only in the past two decades,’ explained Dr Norkienė, whose research focuses on these viruses. 

Most of these viruses are harmless to humans. However, when the immune system is weakened or a person is taking immunosuppressive medication, some polyomaviruses can reactivate and cause serious health problems. For instance, the BK virus is one of the polyomaviruses found in humans. Most people become infected with it in childhood, but the infection generally produces no symptoms. Following a kidney transplant, however, the virus can cause inflammation and damage the transplanted organ. The Merkel cell polyomavirus, meanwhile, is associated with a rare but highly aggressive form of skin cancer.

Thus, it is important for researchers not only to discover new viruses but also to understand the circumstances under which they become dangerous.

Discovering a new virus from a barely visible trace

When we think of new virus discoveries, we tend to picture sophisticated laboratory equipment or major scientific breakthroughs. Yet the first step is often far less spectacular.

It usually begins in the laboratory, with researchers analysing animal samples. The first indication of a potentially new virus may be nothing more than a barely visible DNA band on a gel.

At first glance, such a band may seem unremarkable, but it can provide the first clue to a previously unknown virus.

When examining animal samples, researchers look for genetic traces of viruses. Any positive result from an animal species that has not previously been studied immediately raises a question: is this a known virus, or something that no one has ever described before?

This is where the real detective work begins.

‘Is it really a virus? Could it be laboratory contamination? Does the virus actually live in this animal?’ These are just some of the questions that researchers must answer. 

They reconstruct the virus’s entire genetic sequence, compare it with data stored in international databases, and check whether the same virus has ever been detected before. A single finding is generally not enough: researchers need to establish that it is not merely a chance occurrence. That is why they need to detect a similar virus in more than one animal of the same species and, ideally, across different geographical locations. 

Even then, however, there are usually more questions than answers. One of the most important is whether the scientists have identified a genuinely new virus or simply one that had previously gone unnoticed.

New or just newly discovered?

News of a newly discovered virus often sounds alarming. However, ‘new’ does not necessarily mean ‘recently emerged’. More often, it means something quite different: researchers have detected and comprehensively described the virus for the first time. In fact, most viruses being discovered today are not new to nature – they are new only to science.

Many of the polyomaviruses now being identified in animals have probably been around for thousands, if not millions, of years, but have simply never been studied before.

Nevertheless, new discoveries sometimes raise more complex questions. If a virus causes unusually severe disease in its host, researchers begin to consider whether it has truly been adapted to that species for a long time. In such cases, they seek to answer one crucial question: could the virus have recently crossed over into a new host?

Could a virus cross the species barrier?

‘Our immune system has evolved to cope with constant exposure to viruses, but sometimes the slightest vulnerability is all a virus needs. Some viruses become a threat when they cross the species barrier – that is, when they are transmitted from animals to humans. The diseases they cause are known as zoonoses. Others, including polyomaviruses, are often already present in our bodies and may lie dormant and undetected for years, until a weakened immune system gives them an opportunity to reactivate and cause disease,’ explained VU researcher Dr Norkienė. 

More than 70% of emerging infectious diseases in humans are zoonoses – diseases caused by pathogens transmitted from animals. This is why virologists ask not only ‘What virus have we found?’ but also ‘Could it adapt to a new host?’

How, then, can scientists test something that has not yet occurred in nature?

To do so, they use pseudoviruses – safe surrogates that mimic real viruses. Their viral genetic material is replaced with a fluorescent marker, which means that they cannot replicate or cause disease, even though their outer structure resembles that of a real virus.

If a pseudovirus enters a cell, researchers can detect it using a specialised microscope. In other words, they can observe the initial interactions between the virus and the cell and safely investigate whether the virus could theoretically take the first step towards infecting a new host.

Of course, this does not necessarily mean that the virus will infect a new species in nature. Many factors influence whether this happens – from the host’s immune system to environmental conditions. Such experiments can nevertheless provide initial evidence for or against the hypothesis that a virus may be capable of adapting to a new host.

Experiments of this kind help scientists better understand how viruses recognise cells and which factors determine their ability to infect different hosts. Although this technology remains relatively uncommon worldwide, Vilnius University researchers are among those using polyomavirus pseudoviruses in their studies. 

In collaboration with Dr Christopher B. Buck, a virologist at the US National Cancer Institute, they have developed a rodent polyomavirus pseudovirus technology, enabling safe investigation of how viruses might adapt to new hosts.

When even brewer’s yeast can recognise a viral protein

Sometimes the most fascinating discoveries emerge where they are least expected: during one experiment, researchers found that the major capsid protein of a polyomavirus triggered a strong stress response even in brewer’s yeast.

Brewer’s yeast is one of the simplest eukaryotic organisms, therefore, the finding was particularly surprising. As the yeast cells synthesised the polyomavirus protein, they began to cluster into clumps visible to the naked eye – a mechanism that helps them protect themselves against adverse conditions.

‘Even yeast cells can recognise that a viral protein may be pathogenic and send a warning signal to surrounding cells; thus, we had to work out how to switch off that signal,’ said Dr Norkienė.

Such unexpected observations shed light on how viruses affect living cells and why some of them are so successful at adapting to very different organisms.

Why look for these viruses now?

The search for new viruses is driven by more than scientific curiosity. Climate change, human mobility, growing contact between animals and humans, changing ecosystems, and the increasing number of people with impaired immune systems are all creating new opportunities for viruses to spread. The more we know today about the viruses circulating in nature, the better prepared we will be to face tomorrow’s challenges.

The Vilnius University polyomavirus research group, funded by the Research Council of Lithuania, has already identified several new polyomaviruses that infect animals, although none have been found to pose a threat to humans. Most viruses discovered today are unlikely ever to harm us. Yet this is precisely why it is important to study them before they ever have the chance to become a threat.

Scientists do not know how many such viruses remain hidden in nature. However, each new discovery brings us closer to understanding the invisible world that surrounds us.