There are a number of variables, including the roles of TNF-α in anti-viral immunity independent of a role in WNV BBB permeabilization, the relative importance of WNV BBB permeability at early vs. later stages of infection, and whether WNV entry into the brain via the BBB (as opposed to indirect brain entry via brain penetration of infected leukocytes [34]) is a critical pathway for brain infection and subsequent encephalitis, that are dynamically at play during WNV infection [32], [34], [61]–[63]. Here, TNF is linked to infection.