Intracranial passaging of murine norovirus in Stat1^-/- mice promotes systemic spread and acquisition of lethality.

(A,B) Schematics of intracranial passaging protocol, initiated with 10⁶ PFU CR6, conducted in three parallel “sets” of Stat1^-/- mice (A), and of timing of spontaneous lethality or tissue collection for the three sets of mice (B). (C,D) Heatmaps depicting MNoV genome levels detected by quantitative RT-PCR (qPCR) in designated tissues (C) or stool (D) at time of death as shown in (B), with values ranging from log₁₀ 1.95 to 9.61 (limit of detection at 2.0) for tissues and log₁₀ 2.95 to 7.12 (limit of detection at 3.0) for stool. Each square indicates a single mouse tissue from 24 total mice analyzed. (E) Survival curve of Stat1^-/- mice orally administered 10⁶ PFU CW3 or CR6, or a 1:80 dilution of brain homogenate from Set 1 Round 1 or Round 2 mice. n = 4–9 mice per group over two independent experiments, analyzed by Mantel-Cox test. ***, P < 0.001; **, P < 0.01; *, P < 0.05; ns, not significant.