FIG 9.

Route of spread of VSV infection from the footpad to the brain, blocked by Ifit2 at the sciatic nerve. Within minutes after subcutaneous deposition of VSV in the left footpad, virus drains to the local lymph node in the knee hole, replicates in its periphery, and induces IFN-β, which acts on sciatic nerve neurons innervating the lymph node to induce Ifit2 within less than 24 h after infection. Ifit2 blocks slow VSV spread via the sciatic nerve into spinal cord and brain, thereby preventing limb paralysis. Abbreviations: OB, olfactory bulbs; CX, cortex; MB, “midbrain”; CB, cerebellum; BS, brain stem.