Retroviral diseases of the nervous system: pathogenic host response or viral gene-mediated neurovirulence?

Retroviruses represent an important group of RNA viruses that cause a spectrum of nervous system diseases. Furthermore, newly recognized retroviral infections of the nervous system and some retroviral vectors or proteins used for gene delivery raise potential safety concerns. This article highlights different retroviruses and their causative mechanisms of nervous system disease, or neurovirulence. Specific sequences within retroviral genes might determine the development of neurovirulence. Conversely, neurovirulent retroviruses also activate host immune responses, resulting in a neuropathogenic cascade that is mediated by pro-inflammatory and neurotoxic molecules, ultimately culminating in neuronal death. Thus, retroviral infections of the nervous system illustrate a molecular interplay between distinct infectious agents and pathogenic host responses, which results in neurovirulence.