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. 2012 Jan 27;7(1):e30855. doi: 10.1371/journal.pone.0030855

Figure 9. Proposed microvascular component of brain invasion by NiV in swine.

Figure 9

Fig.9.A . NiV invasion of the central nervous system (CNS) initiated in the nasal cavity leads to virus spread into the brain via neurons [1]. NiV infects cells in contact with neurons: oligodendrocytes, astrocytes and microglia [2]. Astrocytes and microglia are in a direct contact with microvascular endothelial cells (MEC), allowing for direct NiV iter-cellular transmission and infection of the MEC [3]. Infected astrocytes, microglia and MEC recruit leukocytes by release of cytokines (blue arrows). From the incoming leukocytes, the CD6+ T cells can firmly attach to the MEC via the CD6-CD166/ALCAM interaction [4], form transmigration cup, and translocate into the brain parenchyma. (The NK cells and monocytes have low expression of the ALCAM on their surface, and can also transmigrate into the brain. Since the ALCAM-ALCAM interaction is weaker then CD6-ALCAM one, this may be a later event.) The translocating leukocytes can get infected during the transmigration due to intimate contact with NiV infected MEC [5], and spread the virus to the parenchymal cells in the brain [6], thus initiating the CNS invasion via BBB. Fig. 9.B . Alternatively, the recruited lymphocytes can be already infected with NiV. By forming the transmigration cap [4], they can during transmigration infect the MEC [7], spreading subsequently the virus to the in-contact astrocytes and microglia [8], and/or after transmigration across the BBB infect additional parenchymal cells [6]. This mechanism initiates the CNS infection, due to the virus crossing the BBB, and can also apply to invasion of the brain by NiV in other hosts then pigs. Gray star - neuron, blue star - astrocyte, green circle - oligodendrocytes, yellow star - microglia, small brown stars with yellow center - NiV, dark red ovals adjacent to each other - MEC forming the BBB, green dots - schematic representation of the ALCAM, light centered reddish ovals - T lymphocytes with CD6+ markers (dark brown dots), blue arrows - transmigration of leukocytes across the BBB, black arrows - NiV spread.