Wir überwinden Grenzen

Scientists at the Faculty of Medicine in Freiburg are investigating why bird flu viruses are able to overcome the immune defenses of some people / Publication in Science

SARS-CoV-2 has impressively demonstrated that animal viruses can jump to humans. The transmission of pathogens from animals to humans, known as zoonoses, can often lead to serious illnesses and even trigger global pandemics. A research team from the Faculty of Medicine - University of Freiburg, Sun Yat-sen University in Shenzhen, China, and the Chinese Center for Disease Control and Prevention in Beijing, China, is investigating which factors enable or prevent avian influenza viruses from infecting humans. The scientists have now succeeded in identifying a human antiviral protein that plays a key role in preventing human infections with avian influenza viruses. The researchers published their findings in the journal Science on August 20, 2021.

"Until now, it has been difficult to predict why some people become seriously ill with an avian influenza virus. We have now been able to identify a risk factor in humans," says Prof. Dr. Martin Schwemmle, research group leader at the Institute for Virology at the Medical Center - University of Freiburg. Patients infected with the H7N9 avian influenza viruses carried mutations in their MX1 genes more frequently than the general population. The MX1 gene encodes the antiviral protein MxA, which is considered an essential component of genetic virus defense in humans. In previous studies, the Freiburg researchers were able to show that the MxA defense protein inhibits the replication of avian influenza viruses much more strongly than that of seasonal influenza viruses that have already adapted to humans. The mutations now discovered in the publication led to a complete loss of MxA's ability to fend off avian influenza viruses. "The laboratory-based results of our previous work already indicated that MxA could play an important role in the defense against avian influenza viruses. However, until now there has been a lack of evidence from the human population that MxA actually has such a key function in humans," says Dr. Laura Graf, molecular physician at the Institute for Virology at the Medical Center - University of Freiburg.

Easier to identify people with an increased risk of infection

The current study findings show that carriers of inactive MxA proteins have an increased risk of infection with avian influenza viruses and illustrate that MX1 is one of the most important genetic protective factors against avian influenza outbreaks in the human population. "Fortunately, the mutations identified in this study are very rare," says Graf. Nevertheless, the results of this work could help to better protect at-risk groups. The main risk factor for contracting avian influenza viruses is contact with poultry. People who have intensive professional contact with poultry could be specifically tested for mutations in the MxA protein.

Prof. Dr. Georg Kochs, biologist at the Institute for Microbiology and Hygiene at the Medical Center - University of Freiburg and the Chinese researchers Prof. Dr. Yuelong Shu and Dr. Yongkun Chen from Sun Yat-sen University and Prof. Dr. Dayan Wang from the Chinese Center for Disease Control and Prevention were also significantly involved in the study.

Original title of the publication: Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus
DOI: 10.1126/science.abg5953
Link to the study: https://science.sciencemag.org/content/373/6557/918#BIBL

Contact:
Prof. Dr. Martin Schwemmle
Research Group Leader
Institute for Virology
Medical Center - University of Freiburg
Phone: 0761 203-6526
martin.schwemmle@uniklinik-freiburg.de