What is a virus outbreak
Prevent the spread of dangerous viral diseases
Middle East Respiratory Syndrome (MERS) is a serious lung disease caused by a virus called the MERS coronavirus. Around 2,000 people have been infected with this dangerous virus so far, mostly on the Arabian Peninsula. “The viruses are mostly transmitted to humans by infected dromedaries. Dromedaries are kept in Arab countries for meat production or for racing. Since the animals often only suffer from a harmless runny nose, the infection is often not recognized or recognized too late, ”says Professor Stefan Pöhlmann, infection biologist from the German Primate Center, Leibniz Institute for Primate Research in Göttingen. “Fortunately, there have been no large, supra-regional waves of illness so far. Because the virus is currently not transmitted efficiently from one person to another, in contrast to flu viruses, for example. "
The coronavirus family includes - in addition to the MERS coronavirus - other mostly harmless cold viruses. But the dreaded SARS coronavirus is also part of this family. In 2002 and 2003 there was a major SARS outbreak in China, which was dragged to other countries, and as a result of which almost 800 people died.
The MERS and SARS coronaviruses are initially transmitted from animals to humans. In technical jargon, these infections are referred to as zoonotic diseases. These viruses are largely harmless to animals, while infected people can become seriously ill.
But the genetic makeup of the MERS coronavirus is changing, it is mutating. This could create virus variants that are more easily transmitted from person to person. An outbreak from 2015 shows that this danger exists: a single infected traveler who had previously visited the Arabian Peninsula triggered a chain of infection with 186 patients. 38 of them died. Virus variants that had previously unknown mutations were also transmitted. “In South Korea, the virus was transmitted directly from one person to another. This increases the risk that the virus will adapt even better to humans and spread over a large area. We need a test system to identify appropriate virus variants at an early stage. Because then we can initiate suitable countermeasures and contain the spread, ”explains Dr. Markus Hoffmann, a member of the research group from Göttingen. The development of this test system is funded by the Federal Ministry of Education and Research as part of the research association “RAPID - Risk Assessment in Pre-Pandemic Respiratory Infectious Diseases”.
Virus activation as a starting point for the test system
In order for the MERS coronavirus to multiply in the body, it uses - like all viruses - certain proteins and enzymes from its host. Stefan Pöhlmann's team was able to show that the host enzyme TMPRSS2 cleaves the viral spike protein in the virus envelope and thus activates it. The researchers are now investigating whether variants of the MERS coronavirus use this host enzyme with different degrees of efficiency - and whether this affects its transferability. "If so, a test system could come into play here: It could measure the efficiency of TMPRSS2 use and thereby enable predictions about transferability," explains Hannah Kleine-Weber, who is carrying out relevant studies as part of her doctoral thesis. The researchers have already identified the point at which TMPRSS2 cleaves the virus' spike protein. “That is why we also know which structures we need to keep an eye on in order to identify virus variants that are more effectively split,” adds the scientist.
To test their approach, the researchers first use defective viruses that carry the spike protein but are unable to reproduce and therefore pose no danger. With the help of these particles and the newly developed cell culture system, variants of the spike protein can be identified that show an altered TMPRSS2 use. The corresponding virus variants are then produced. In cell cultures and in animal models, the extent to which the efficiency of TMPRSS2 use and its transferability are related is then investigated.
TMPRSS2 as a potential drug target
But not only the MERS coronavirus uses TMPRSS2 for its reproduction. Other viruses are also activated in the body in this way, including the influenza A virus, which triggers the flu. The test system could therefore also make it possible to predict the transferability of other, much more common viruses in the future.
Infection experiments with rodents also suggest that TMPRSS2 could be a good target for drugs. “In the animal model, an inhibitor that turns off TMPRSS2 and related enzymes also suppresses the development of flu and SARS. A similar effect can also be expected for MERS, ”says Pöhlmann. "We are therefore also researching which active ingredients we can use to inhibit TMPRSS2."
Prof. Dr. Stefan Pöhlmann
German Primate Center
Dept. of Infection Biology
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