Figure 2.

Viral Modulation of BBB Function

Viruses might impact on TJ integrity via direct and indirect mechanisms: (1) virus detection by brain endothelial TAM receptors in conjunction with type I IFN signaling enhances TJ integrity (Miner et al., 2015); (2) nonstructural protein (NS)1 secretion by flaviviruses might decrease TJ integrity, increasing barrier permeability; (3) PRR signaling during viral infection of astrocytes leads to type I IFN expression which has been shown to improve BBB function via intercellular crosstalk with brain endothelium (Daniels et al., 2014); (Pfefferkorn et al., 2015); and (4) secretion of transactivator protein (TAT) during CNS infection with HIV-1 induces pericyte expression of PDGFβ, which disrupts BBB junctional proteins and promotes pericyte migration away from the vasculature (Niu et al., 2014), (Winkler et al., 2010).