Interferon Deficiencies in Viral Disease

We are interested to understand human genetic and non-genetic factors in the interferon (IFN) system that modulate susceptibility to viral infection and disease severity (reviewed in Stertz & Hale, Trends in Microbiology, 2021). In particular, we recently partnered with colleagues at the University Hospital Zurich to confirm reports that autoantibodies neutralizing the function of IFNs are prevalent in an unexpectedly high proportion of patients critically-ill with COVID-19. In this study, we could also demonstrate that anti-IFN autoantibodies appear to increase susceptibility to other viruses, such as herpesviruses (Busnadiego et al., PLOS Biology, 2022).

We are now actively engaged in studies to evaluate the prevalence of anti-IFN autoantibodies in other patient populations, to understand what factors influence their production and levels in selected individuals, and to assess the basis for their contribution to non-COVID viral disease susceptibility. Our overall goal in this area will be to establish conceptual frameworks for new targeted diagnostics or therapies in personalized medicine.