Fig. 1.

Routes of arbovirus entry into the central nervous system (CNS). (A) Infection of olfactory sensory neurons (OSN) in the olfactory neuroepithelium (ONE) following intranasal inoculation or ONE infection from fenestrated vessels (FV). CNS entry occurs after viral migration through the cribiform plate (CP), subsequent infection of mitral cells (MC) at the glomeruli (G) of the olfactory bulb (OB), and dissemination along neuronal tracts. (B) Retrograde transport of virus along axon microtubules (MT) of peripheral neurons facilitates entry into the CNS at the spinal cord. (C) Virus entry through the blood–brain barrier (BBB) is dependent on transcellular transport by brain microvascular endothelial cells (BMECs) of virions or paracellular migration of virions following disruption of tight junctions (TJ). Infected leukocytes may also facilitate CNS entry via paracellular or transcellular extravasation – the “Trojan Horse” model FV = fenestrated vessel; BMEC = brain microvascular endothelial cells