Five Questions about Viral Trafficking in Neurons

One of the most exciting areas in biology is the nervous system and how it works. Viral infections of the nervous system have provided exceptional insight at many levels, from pathogenesis to basic biology. The nervous system has evolved rather complicated barriers that facilitate access to nutrients and contact with the outside world, but block entry of pathogens and toxins [1]. However, when these barriers are reduced for any number of reasons, nervous system infections are possible. When they occur, they can be devastating and, even with good antiviral drugs, difficult to manage. Viral infections can enter the brain via the blood (e.g., HIV, various encephalitis viruses) or by spread inside neurons from the body surface (e.g., rabies and alpha herpes viruses) [2,3]. In vertebrates, the nervous system comprises a peripheral collection of neurons (the peripheral nervous system, PNS) and a central set found in the brain and spinal cord (the central nervous system, CNS). While neurons are central players in neurobiology, it is important to realize that the majority of cells that comprise the nervous system are highly specialized, nonneuronal cells (e.g., different types of glial cells) [4]. Cells of the immune system also engage with and signal to the PNS to affect changes in the CNS [5]. We will focus on neurons, despite the other cellular complexity, because neurons provide direct avenues for viral infection. Recognition that viral infection follows nerve pathways enabled the development of viruses for neuronal circuit tracing [6–8].