Nexus of virus and brain: recent advances in flavivirus and enterovirus neuro-infection

The global prevalence of neurotropic viruses is increasing annually, with no effective treatments available. Viral entry into the brain involves a complex interplay of host and viral factors, such as tight junction complexes, immune regulators, and viral protein polymorphisms. After establishing an infection in the brain, neurotropic viruses can trigger immune cell activation, robust inflammatory responses, and synaptic disruption, contributing to both acute and chronic neuropathology, including accelerated neuronal ageing and neurodegeneration. A wealth of studies has focused on the molecular mechanisms underlying the neurovirulence and neuropathogenesis of clinically relevant neurotropic RNA viruses, revealing critical insights into their interactions with host cells and immune response. However, despite such advances, a disparity in knowledge on how these viruses enter the brain remains. In this review, significant progress within the last 2 years, as well as research niche and challenges in unravelling the neuropenetrance of clinically relevant neurotropic flaviviruses and enteroviruses in causing neuro-associated pathology will be discussed.