Here, we investigated the role of TLR4 in the induction of BBB permeability and disease in mice during VEEV infection using the C3H/HeN model of VEEV infection with the TC-83 vaccine strain, which causes encephalitis and death in C3H/HeN (TLR4WT) mice when intranasally instilled, in parallel with TLR4-defective C3H/HeJ (TLR4mut) mice. This evidence concerns the gene TLR4 and viral encephalitis.