Dissemination of reovirus T3D to the CNS is limited by type I IFN responses and older age but not inefficient retrograde axonal transport. IFNAR+/+ and IFNAR−/− mice were inoculated intramuscularly with 107 PFU total of nine genetically marked reoviruses, with or without additional muscle damage. Viral titers were determined by plaque assay, and viral population diversity was determined using a hybridization-based assay. Reovirus T3D titer (A) and viral population diversity (B) in tissues harvested from adult IFNAR+/+ or IFNAR−/− mice with or without muscle damage. Tissues were collected at 72 hpi. (C) Reovirus T3D titer in tissues from adult mice collected at 7 d post-inoculation. Reovirus T3D titer (D) and viral population diversity (E) in tissues from 3-day-old IFNAR+/+ or IFNAR−/− mice. Tissues were collected at 72 hpi, prior to disease onset. Results are presented as mean +/− standard error of the mean from 5-9 mice per condition. Values that are significantly different, as determined by the Mann-Whitney test, are indicated by asterisks as follows: *, P < 0.05, **, P < 0.005, ***, P < 0.0005. Mus., Muscle, SN, Sciatic Nerve, SC, Spinal Cord, Br., Brain. ND, none detected.