PhD defence D. (Danny) Noack

Below is a brief summary of the dissertation: 

Orthohantaviruses are viruses that are found in rodents in nature, almost everywhere in the world, including in the Netherlands. These rodents don't usually get ill from an orthohantavirus infection, but humans can become seriously ill if they become infected with the virus by inhalation of dust from dried urine, feces, or saliva of infected rodents. To better understand how the disease develops, researchers need laboratory models that simulate the human body. The research in this thesis shows that orthohantaviruses infect cells lining blood vessels, called endothelial cells, in various organs in both humans and rodents. Our research shows that the way these infected endothelial cells interact with cells from the immune system is a key factor in how the disease progresses, and this differs between humans and rodents during the early stages of infection. To study this more effectively, we developed three-dimensional blood vessels in the laboratory that experience artificial blood flow, and therefore more closely resemble blood vessels in the human body compared to current methods where cells are grown on flat plastic surfaces without exposure to fluid flow. Using these blood vessels, we investigated the effects of Puumala orthohantavirus, responsible for the most orthohantavirus infections in the Netherlands, and found that the effects indeed more closely match what occurs in patients infected with Puumala orthohantavirus. Additionally, we developed a new animal model where miniature human lungs grow on the backs of mice. This model can be used to study how orthohantaviruses affect the human lungs, but also to test if new drugs are working against one or multiple orthohantaviruses. Previously, this was not possible within the same animal model.