Breaching the BBB may precede neuroinvasion and occurs via the compromised permeability of BCECs or the NVU, and in WNV infection, the underlying mechanisms of CNS entry and infection may involve cytokines like IL-6 and TNFα, semaphorin 7A, metalloproteinases, a ‘Trojan horse’ route utilizing infected immune cells, direct axonal retrograde transport, infection via the olfactory bulb and direct infection of cells of the NVU or neuron-to-neuron infection [134,147,148,149,150]. Here, IL6 is linked to infection.