Role of the blood-brain barrier in rabies virus infection and protection

Rabies is an acute, progressive encephalitis caused by infection with rabies virus (RABV). It is one of the most important zoonotic infections and causes more than 70,000 human deaths annually (http://www.rabiescontrol.net). It has long been held that a rabies infection is lethal in humans once the causative RABV reaches the central nervous system (CNS); however, this concept was challenged by the recent recovery of a small number of rabies patients. An analysis of these patients revealed that the bloodbrain barrier (BBB) played a major role in protection against the virus. The main reason for the survival of these patients was enhanced BBB permeability after infection with the causative agent (usually bat-originated RABV showing reduced pathogenicity), which allowed immune cells to enter the tissues of the CNS and clear the infection (Willoughby et al., 2005). These findings have been confirmed in animal infection experiments (Wang et al., 2005; Roy and Hooper, 2007, 2008; Faber et al., 2009). Thus, the BBB has attracted the attention of scientists interested in the pathogenesis of, and therapeutic approaches, for rabies. This paper introduces the role of the BBB in rabies infections and protection of the CNS and provides insight into future treatments for patients with clinical rabies.