FIG 1 .

Two discrete TLR pathways regulate SARS-CoV pathogenesis. (A and B) Profiles from microarray analysis of MyD88 (A) and TLR3 (B) RNA expression results in 20-week-old C57BL/6J mice infected with 10³, 10⁴, or 10⁵ PFU of SARS-CoV indicate that differential levels of gene expression occurred at day 2 postinfection (a single asterisk [*] indicates differential expression determined by a >1.5 log_2-fold increase in expression compared to the results seen with mock infections; P < 0.05). (C and D) Infection of TLR3^−/− and C57BL/6NJ mice with SARS-CoV showed significantly greater weight loss in TLR3^−/− mice than in wild-type mice (**, P < 0.01; ***, P < 0.001, by nonparametric Mann-Whitney test, where values indicate the mean percent starting weight and error bars indicate standard deviation) (C), and viral titers were significantly higher in the TLR3^−/− mice than in wild-type mice (***, P < 0.001 [by Student’s unpaired t test]) (D). TLR3 signaling through the TRIF adaptor protein activated innate immune antiviral signaling programs in a MyD88-independent manner, indicating that at least two discrete TLR signaling pathways are involved in SARS-CoV pathogenesis. DPI, day postinfection.