, 1998). The Trojan horse mechanism of transport across BBB is considered to play a crucial role in the pathogenesis of viral meningitis in the late phase of AIDS. This model has gained rapid favor; however, recent studies change this model by showing that the vast majority of virions transmitted in trans originate from the plasma membrane rather than from intracellular vesicles (Cavrois et al., 2008). The mechanisms of BBB disruption during retroviral-associated pathologies are not fully understood yet. Most of the studies are focused on the effect

of soluble molecules secreted by infected lymphocytes on BBB functions and intercellular TJ organization. In case of HIV infection, the viral protein Tat has been shown to induce cell apoptosis and disruption of the TJs (Andras et al., 2003). In short, Tat-mediated downregulation BMS-777607 cell line of claudin-5 plays an important role in altered integrity of BMEC that aids viral transport across BBB (Andras et al., 2005). West Nile virus (WNV)-associated encephalitis is characterized by disruption of the BBB, enhanced infiltration of immune cells into the CNS, microglial activation, inflammation, and eventual loss of neurons (Glass et al., 2005; Sitati et al., 2007). WNV gains entry into the CNS via the transcellular pathway, without compromising

the BBB integrity instead AZD1208 cell line of paracellular pathway (Verma et al., 2009). Tick-borne encephalitis

(TBE) virus causes severe encephalitis with serious sequel in humans. The mechanisms underlying how TBEV gains access to the CNS are not completely elucidated. There are several hypothetical routes for TBEV traversal across BBB. These include (i) cytokine-mediated BBB breakdown, (ii) “Trojan horse” theory, and (iii) viral entry into the BMECs, transcytosis, and the release of virus into the brain parenchyma (Ruzek et al., 2011). Proteins from microbial pathogens are the dominant virulence factors mediating entrance to the CNS; however, various nonproteinous microbial components including lipopolysaccharide, LTA, glycolipids, and hyaluronic acid contribute to breakdown of the BBB. Lipooligosaccharide on the outer membrane is an important inflammatory agent Liothyronine Sodium in the CSF. Recent studies have demonstrated that lipooligosaccharide and lipopolysaccharide containing outer membrane vesicles provoke meningeal inflammation, increase concentration of leukocytes, and change permeability of the BBB (Cope et al., 1990). Hyaluronic acid of C. neoformans capsule facilitates the transport via BBB (Jong et al., 2007). Several hyaluronic acid receptors have been identified on various ECs; however, the only receptor on BMEC interacting with hyaluronic acid is CD44, the most common hyaluronic acid receptor in vertebrates. This interaction initiates the events of the entry at the BMEC membrane rafts (Jong et al., 2008).