**3.2 Signalling pathways in BBB disruption in HIVE/SIVE**

We have recently shown that viral infected macrophages are important in disruption of the BBB *in vitro* (MacLean et al., 2004a, MacLean et al., 2004b), *ex vivo* (Ivey et al., 2009b, Renner et al., 2011) and *in vivo* (Renner *et al.*, in press). The precise mechanisms of BBB disruption are a subject of active research by numerous groups (Luabeya et al., 2000, Andras et al., 2003, Kanmogne et al., 2005, Kanmogne et al., 2007, Persidsky et al., 2006). All of these distinct signal transduction mechanisms have a common factor, however: the tight junctions are linked to the actin cytoskeleton, and the dynamics of the cytoskeleton are therefore important regulators. The importance of cytoskeleton activation will be revisited later when discussing glial cell activation.
