Hijacking the host: molecular strategies of neurotropic enteric viruses (360G-Wellcome-325749_Z_25_Z)

Many common enteric viruses can also infect cells of the central nervous system (CNS). Such neurotropic viruses infect >50 million people annually, causing encephalitis, meningitis, and other complications. Picornaviruses and astroviruses stand out for their ability to infect cells of both gut and neuronal origins. This project seeks to understand the molecular basis of how enteric viruses can display both neurovirulence and gut-specific replication. This will be achieved by focusing on three fundamental aims. (1) Elucidate host-pathogen interactions to uncover the molecular processes underlying different stages of infection, supported by defining the cell-type specificity of virus infection in both intestinal and neuronal cells. (2) Identify tissue- specific regulation of viral protein synthesis and specialised CNS host responses. (3) Uncover the roles of viral RNA structures in virus replication and neurovirulence. Investigating these mechanisms in two diverse virus families will reveal common and virus-specific principles in host-pathogen interactions along the gut-to-brain axis. This research will build a transformative platform applicable to other viruses and hosts, where diverse tropisms shape the diseases they cause. These findings will enhance our understanding of tissue-specific properties of clinically important pathogens, advancing the development of therapeutics and vaccines, and informing public health measures.