Michael Veit, a virology lecturer at Freie Universität Berlin, studies how pathogens are transmitted from animals to people. His goal is to be able to predict the importance of mutations in the virus with greater accuracy so that in cases of doubt, people can be warned in time if a certain virus may become dangerous to humans as well as animals.
To that end, Veit has teamed up with researchers from Singapore, the UK, and the United States to form an international network, the “Molecular Patterns of Influenza Virus Envelope Adaptation to Interspecies Transmission” project, which is receiving about 1.3 million euros in funding from the Human Frontier Science Program (HFSP), an aid program for transcontinental cooperative research projects in the life sciences, over the next three years.
Virus transmission routes differ between animals and humans. Infection between humans typically takes place through airborne droplets, such as those expelled when a person sneezes. In waterfowl, which are especially susceptible to flu, the virus typically enters the body through the bill and is then excreted again through the digestive tract.
Project Funding for Next Three Years Is 1.3 Million Euros
The virus itself is encased by a layer called an envelope that consists of 400 to 500 different lipids – non-water-soluble fats that can be either liquid or solid, depending on the temperature. This envelope protects the virus’s genetic material when the pathogen is outside the body, and for optimum protection, it should be solid. Because the virus cannot multiply on its own, it requires a host cell to reproduce.
That means it has to travel around and “dock” onto a host cell. For the virus to insert its own genetic material into the host cell, the protective lipid envelope has to become liquid again – it has to melt. Only then can the virus genes be released and penetrate into the cell, which the pathogen then uses to reproduce its own genetic material, producing new viruses.
“For the virus to be able to pass from an animal to a person, it has to mutate, meaning adapting its genetic material,” Veit says. He assumes that when this mutation occurs, the lipid envelopes around the viruses change as well.
Since birds and humans have different body temperatures and different lipids have different melting points, Veit suspects that when viruses pass from birds to humans, the melting points of the lipid envelopes also adapt accordingly. With this in mind, he plans to study the structure of the lipid envelopes of various animal and human bird flu viruses to see whether they are in fact different, and if so, at what temperature the envelopes melt.
If it turns out that these differences do in fact exist and a lipid envelope does not melt until it reaches 40 degrees Celsius, for example, the virus contained inside the envelope would pose a risk to waterfowl – their body temperature is 42 degrees Celsius – but not to humans. The normal human body temperature is 37 degrees Celsius, and it is even lower in the lungs, which are constantly in contact with the air outside the body. That means the temperature would be too low to cause the envelope to melt. If a new bird flu virus were found among animals, scientists could simply take a sample of the virus and easily see whether the new type could also pose a risk to humans.
To check his hypothesis, Veit is currently culturing human and avian virus cells in Berlin. Once the cultures have grown, the lipids will be extracted. At that point, the plan is to send the substances to Singapore, where cell biologist Markus Wenk will study them to see what kinds of lipids are contained in the lipid envelopes of different flu viruses and whether there are differences between the envelopes of human viruses and avian ones.
After that, the envelopes’ melting points will be determined. This will be handled by biophysicist Lukas Tamm at the University of Virginia Medical School in Charlottesville. Finally, Kay Grünewald of the University of Oxford will study the viruses in England, using a newly developed electron microscope technique to see whether the different viruses also vary in terms of their fine structures.
It is likely that it is the membrane proteins embedded in the envelope that determine what lipids the envelope is made of. Exchanges of certain amino acids, the building blocks of proteins, could cause other lipids to be built into the envelope, potentially changing its melting point.
If this hypothesis is correct, it would be possible to predict from the amino acid sequences of the viruses whether certain lipids could occur in a virus – such as lipids that melt at temperatures of 37 degrees Celsius, making the pathogen a hazard to humans. “Of course, it would be a fantastic result if, in the end, we had another parameter to be able to predict based on the amino acid sequence whether a new avian virus can be transmitted from person to person,” Veit says.
If the scientists’ suspicions are confirmed, there would also be an impact on media headlines in the case of future bird flu epidemics. When a new type of virus was found in poultry houses, newspapers could then run headlines such as “Pathogen test shows new bird flu virus harmless to humans” in the best case. And if not, scientists would have gained enough time to produce a vaccine.