Differential Susceptibility of hiPSC-Derived Neural Progenitors and Neurons to Measles Virus Infection Reveals Unique Neuronal Budding and Viral Mutations

Abstract Measles virus (MeV) can cause severe neurological complications such as measles inclusion body encephalitis (MIBE) and subacute sclerosing panencephalitis (SSPE), but the mechanisms of MeV infection in the human Central Nervous System (CNS) remain poorly understood. In this study, we modeled MeV infection in the CNS using neural progenitor cells (NPC) and cortical neurons derived from human-induced pluripotent stem cells (hiPSC), evaluating infectivity, viral replication and mutation, and neural function after infection. NPC were highly susceptible and permissive to infection, forming cytoplasmic inclusion bodies, undergoing apoptotic death, but producing infectious particles. In contrast, neurons supported viral replication but did not produce infectious progeny, despite the visualization of budding viral particles by Transmission Electron Microscopy (TEM). Our findings advance the understanding of MeV neuropathogenesis and support the utility of hiPSC-derived neural models for studying neurotropic viral infections since we could reproduce key aspects of MeV neuronal infection.