The respiratory tract, a major barrier to airborne viruses
Several viruses, particularly those with pandemic potential, follow an airborne route of infection by invading the organism through the respiratory tract. Among those, respiratory syncytial virus (RSV) is a major cause of severe infections in babies and infants with more than 30 million hospitalizations and more than 100’000 deaths each year worldwide. So far, there is no licensed vaccine available, and therapeutic options are limited. In young ruminants, RSV infections are leading to high levels of morbidity and mortality with no optimal prophylactic and therapeutic measures available. To understand the mechanisms of human and bovine RSV disease and discover novel therapeutic approaches, we have set up a unique set of tools. This includes primary cultures of the conducting airways, distal lung explants, and an animal model of early-life RSV infection.
Molecular basis of neurovirulence
Various pathogens can invade the nervous system and cause severe neurological disorders. We mainly focus on neurotropic flaviviruses which account for numerous outbreaks worldwide. Notably, the incidence of infections caused by these arthropod-borne viruses is on the rise due to anthropogenic factors such as climate change, deforestation, and globalization. As such, zoonotic flaviviruses like Zika virus (ZIKV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV), represent a significant burden to global health. To elucidate flavivirus cell tropism and mechanisms of neurovirulence, we use neural organoids, a sophisticated in vitro model of the nervous system. Ultimately, we aim at providing the basis for intervention strategies to prevent and treat neurological manifestations occurring during flavivirus outbreaks.
Mechanisms of vertical transmission
Certain pathogens can cross the placental barrier, a route of infection termed vertical transmission. When transplacental transmission occurs, viruses may gain access to the developing fetus, potentially leading to irreversible damage. To study the barrier function of the placenta and explore the mechanisms this barrier mounts against viral infection, we apply models such as placental tissue explants and trophoblast organoids. While term placenta explants allow us to model infection during late gestation, trophoblast organoids can recapitulate virus infection during early pregnancy. We primarily focus on emerging pathogens with a zoonotic origin such as SARS-CoV-2 and flaviviruses, which can cause adverse fetal outcomes in humans and animals.
