Tissue tropism and protective effect on mouse survival of CVB3-miRTs are controlled by miRNA machinery. (A) BALB/c mice were infected i.p. with the engineered or control CVB3. Viruses isolated from the heart were analyzed by a standard plaque assay at 3, 5, and 7 days postinfection. Virus titers (PFU/g) were normalized to tissue mass. Virus titer values represent the means ± the SD of three independent experiments (n = 5 mice/group). (B) Histological analysis of CVB3 infection in the heart tissues of mock-infected mice or mice i.p. infected with 105 PFU of CVB3-WT or the CVB3-miRTs. Heart sections were prepared 5 and 7 days postinfection. Examples of necrosis, calcification (black arrows), and infiltration (blue arrow) are shown. Original magnification, ×200. (C and D) Survival of BALB/c mice infected with CVB-206T, CVB-3*T, or control viruses (n = 20 mice/group). (C) Survival of BALB/c mice after infection with 105 PFU—the LD50 for CVB3-WT—of the indicated virus. (D) Survival of BALB/c mice infected with 106 PFU—the LD100 for CVB3-WT—of the indicated virus.