A perilous leap across the species barrier

(From "Horizons" no. 114 September 2017)​​​

​Camels are indispensable pack animals in the desert. But these well-loved creatures have become an unpredictable threat to humans on account of the dangerous viruses they carry. Their airways harbour coronaviruses that can provoke fatal pneumonia in people. Since the first cases of Middle East Respiratory Syndrome (MERS) were registered in the summer of 2012, a total of 1,641 people had been infected in Saudi Arabia with the coronavirus up to June 2017. Forty-one percent of them have died. When a disease can be passed from animals to humans, it's a phenomenon known as zoonosis.

"This coronavirus is a typical zoonosis, such as we have repeatedly observed in recent years", says Volker Thiel, professor for virology at the University of Bern and Head of Virology at the Swiss Federal Institute of Virology and Immunology (IVI). Many pathogens often circulate inconspicuously in animals that they do not affect. Occasionally, a chance leap across the species barrier can occur – such as into humans. The reactions can be violent, and in the worst cases, deadly to the new host. Ebola, SARS, MERS and Zika are the last cases in a long series of zoonoses. Rabies, the plague, AIDS and bird flu testify to earlier occurrences.

Diversity and cross-species infection

Volker Thiel was very much in demand in the winter of 2002 when serious cases of the new lung infection called 'Severe acquired respiratory syndrome' (SARS) occurred in southern China. He was one of the first to receive and sequence viral isolates from patients. Within a short space of time, epidemiologists were able to identify a coronavirus as the pathogen. By comparing it with the genome of harmless viruses, researchers were able to find the mutations that had been necessary for it to cross the species barrier into humans. "It needs surface molecules that can bind themselves firmly to the docking sites on human lung cells", says Thiel. They also found out how the virus was able to mitigate signals from the immune system.

"In a blood sample, whether from animals or humans, there are thousands of individual viruses that are all slightly different from each other", says Thiel. This high mutation rate creates many variants, which increases the chance that one of them will be able cross the species barrier to attack a new host. On the other hand, this variability explains a phenomenon that can often be observed: after the initial intense infections, the virus stops adapting, because it cannot proliferate if it kills its host. "We were able to observe this weakening in outbreaks of SARS and also of Ebola", says Thiel.

In the case of SARS, the coronaviruses most likely jumped from mongooses to humans – presumably when these animals were slaughtered; they are regarded as a delicacy. Coronaviruses circulate in many animals, though primarily in bats and rodents, as an international team of researchers under Simon Anthony recently proved at Columbia University in New York. Teams in 20 countries in Latin America, Africa and Asia investigated bats, rodents and apes in a study lasting several years. They analysed tissue samples for viral genetic material, and found coronaviruses in ten percent of the bats they examined; in rodents and apes it was less than one percent. The diversity of the coronaviruses was also by far the greatest in the bats. "Bats are the most important reservoir for coronaviruses", Anthony concludes.

One reason for this lies in the robust immune system of bats, which can keep their viral tenants in check. Another reason can be found in the large-scale social communities in which up to several million animals can live in close contact with each other. This facilitates the exchange of viruses. Furthermore, the bat species is extraordinarily large and varied. When humans enter regions they have never inhabited, such as the rainforests of Africa and South-East Asia, viruses are given a new opportunity to spread.

Colds from camels

Extensive specimen collections from the jungles of Central Africa have shown that fruit bats are the origin of the highly dangerous Ebola virus. We know that SARS and MERS also come from bats, because almost identical viruses have been found in these animals. "We assume that the MERS virus jumped from bats to camels at some point in the past, and that it has meanwhile established itself in its new host", says Thiel. From there, it now regularly jumps across to the humans who live near the animals. Thiel and his team have been able to show that the MERS coronavirus also displays surface molecules that can bind themselves easily to lung cells. Such changes of host, from camels to humans, obviously already took place in the distant past, hundreds of years ago. In collaboration with the renowned virologist and co-discoverer of the SARS virus, Christian Drosten in Berlin, Volker Thiel recently found coronaviruses in camels that are closely related to one of the cold viruses found today in humans.

It is logical to assume that this virus also caused deadly infections at the time it first took humans as its host, and that it weakened over the course of time. Comparisons between the coronavirus in camels and the cold virus in humans have provided initial information about the steps involved in the process of genetic adaptation. "We can see differences in the genome, but don't yet understand their meaning", says Thiel.

Bats are by no means the only bearers of highly dangerous pathogens. Extremely hazardous strains regularly occur in an exchange between pigs, birds and humans. This is why new influenza pathogens from pigs (H1N1) and waterfowl (H5N1) are being closely monitored by virologists. Christian Griot, Director of the Swiss Federal Institute of Virology and Immunology, sees these influenza viruses as presenting the biggest risk at present. Such a virus could spread across the world in a very short space of time.

This is not yet the case with the coronavirus that causes MERS. But that may change. Every new human infection offers the virus another opportunity to adapt itself better and to infect the upper respiratory tract, which it at present finds difficult. "If it were to spread more easily from one human to another, then we would have reason to fear a worldwide pandemic with very many victims", says Volker Thiel. And it is getting more and more difficult to prevent outbreaks. Meanwhile, the MERS virus has established itself firmly in the camel population on the Arabian Peninsula. These proud ships of the desert are now a ticking time bomb.

Stefan Stöcklin is an editor in the Communication Department of the University of Zurich.

E. Kindler et al.: Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication. EPLoS Pathog (2017)

V. M. Corman et al.: Link of a ubiquitous human coronavirus to dromedary camels. PNAS (2016)