Abstract
Viral infections of the central nervous system (CNS) represent a significant burden to human health worldwide. Neurotropic viruses must travel from a body entry gate up to the CNS, where they infect local cells and potentially cause neurological disorders. The brain is protected from blood-borne pathogens by the so-called blood-brain barrier (BBB), an endothelial cell wall exhibiting extremely low permeability. Bacteria, fungi, parasites, and viruses have evolved various powerful strategies to reach the brain [1-3]. However, it is unclear whether the different strategies coexist or a main pathway prevails while the others are marginal. Here, we describe the main strategies for viruses to cross the BBB, with a particular focus on flaviviruses, which represent important emerging human neurotropic pathogens. The aim of this review is to put into perspective the four main ways to cross the BBB and to re-visit these concepts in the light of new technical developments.