Beyond the neuron: the role of glial cells in viral neuropathogenesis

The human central nervous system (CNS) is multicellular and complex. Sequelae of acute or chronic viral CNS infections can last a lifetime, and therapeutics are limited. Neurotropic viral infections can cause many manifestations, including encephalitis, meningitis, and paralysis. Most studies of neurotropic viruses focus on infection, dysfunction, and cellular death of neurons; however, neurons comprise only half of the cells of the human CNS. The remainder of the CNS is made of glial cells, such as astrocytes, microglia, oligodendrocytes, and neural progenitor cells (NPCs), which can give rise to neurons or glia. Glial cells serve critical maintenance and neuroprotective roles, including in response to infections. This review describes what is currently known about acute neurotropic viral infection of non-neuronal cells for human viral pathogens. Recent development of techniques to assess infection at the single-cell level, as well as increased complexity of human multicellular models of the brain and spinal cord, will expand our understanding of viral tropism and neuropathogenesis, potentially revealing novel therapeutic targets for these severe infections.