Viral disruption of the blood-brain barrier

Abstract

The blood-brain barrier (BBB) provides significant protection against microbial invasion of the brain. However, the BBB is not impenetrable, and mechanisms by which viruses breach it are becoming clearer. In vivo and in vitro model systems are enabling identification of host and viral factors contributing to breakdown of the unique BBB tight junctions. Key mechanisms of tight junction damage from inside and outside cells are disruption of the actin cytoskeleton and matrix metalloproteinase activity, respectively. Viral proteins acting in BBB disruption are described for HIV-1, currently the most studied encephalitic virus; other viruses are also discussed.

Figure 1

The neurovascular unit and junctions between endothelial cells. (a) cross-section of a brain microvessel, showing cells of the neurovascular unit. Neurons and their contacts with astrocytes are not shown. Cells in the lumen (bloodstream) include red blood cells, lymphocytes, monocytes, and neutrophils (not shown). Note the two basement membranes; the space between them is known as the perivascular space. (b) Enlargement of an endothelial cell-cell junction. Major molecules of the tight junction and adherens junction are shown; no order of the tight junction proteins within the tight junction is implied by the figure. Abbreviations: JAMs, junctional adhesion molecules; ESAM, endothelial cell-selective adhesion molecule; CAR, Coxsackie and adenovirus receptor; ZO, zona occludens. The figure is based on figures in [7,95].