Differentiation of Human Neurons and Neuron-Like Cells to Study VZV Neuronal Infection

Varicella zoster virus (VZV) is a neurotropic human herpesvirus that causes varicella upon primary infection and establishes latency in neurons of the peripheral nervous system. The reactivation of latent neuronal infection results in herpes zoster and, in rare cases, severe neurological complications. VZV is human specific, and the investigation of VZV-neuron interactions requires human neuronal models, presenting challenges due to limited accessibility and ethical constraints. Here, we describe approaches to generate mechanoreceptive sensory neurons from small-molecule-derived neuronal precursor cells (smNPCs) and to differentiate neuron-like cells from the SH-SY5Y neuroblastoma cell line. These two distinct neuronal models serve as valuable tools to study VZV infection. Additionally, we provide a protocol to prepare VZV cell-free virus and to conduct neuronal infection, facilitating further research on the pathogenesis associated with VZV neurotropism.