Human organoids for virology

Understanding neurological infectious diseases is needed as they are a major threat to human health. Poliovirus has led to debilitating outbreaks of paralytic disease, and the polio-related enteroviruses are still the most common causes of viral brain infections. Neuro-infections lead to high hospitalisation rates and long-term complications with often no treatment available. Neuropathogenicity of human viruses is notoriously difficult to study in animal models. Therefore, suitable human experimental models are needed such as organoids, which accurately mimic the human physiological environment. The Amsterdam UMC (AMC) has already established gut, airway, and brain organoids as tools for studying viral infections and viral vector-based gene therapy. To further study virus-host interplay, advanced organoid models are needed. In the ADVOCATE study, the Amsterdam UMC and VectorY bring in means and expertise to expand knowledge on neurovirulence and countermeasures. Amsterdam UMC has expertise in establishing stem cell-derived organotypic cultures for studying viruses and antiviral testing. VectorY has an innovative platform for delivery of antibodies to the central nervous system and has developed a unique neuro-muscular organoid (NMO) model. The ADVOCATE study is structured into two work packages. In WP1, a NMO will be implemented for neuro-infection of non-polio enteroviruses and assessing how these viruses affect NMO function. WP2 will focus on potential antiviral strategies by studying the spread of vectorised antibodies in NMO and testing of existing antivirals against neurovirulent enteroviruses with the aim to develop efficient antiviral strategies. Overall, the ADVOCATE study will deliver an advanced NMO model for virology which lowers the barriers for the implementation of organoids in virology and enable a smooth transition to animal-free innovations.