Figure 2.

Pivotal role for HDAC3 in the antiviral response in vivo. (A) Survival (Kaplan-Meier curve) of 8-week-olds HDAC3^fl/fl (n = 5, 7) and HDAC3^fl/fl Lyz2-Cre mice (n = 5, 7) intraperitoneal injected with VSV-GFP or HSV-1-GFP (7 ×10⁷ PFU/g, 2 × 10⁷ PFU/g) [plaque-forming unit] monitored for 48 h or 2 w. (B) ELISA analysis of IFN-β in the sera from HDAC3^fl/fl (n = 7, 10) and HDAC3^fl/fl Lyz2-Cre mice (n = 6, 10) after VSV or HSV-1 infection. (C) VSV load in the liver, spleen, lungs or HSV load in the brain of HDAC3^fl/fl or HDAC3^fl/fl Lyz2-Cre mice (n = 5 per group) after intraperitoneal infection with VSV (24 h) (as in left) or HSV-1 (5 days) (as in A), assessed by endpoint-dilution assay and presented as 50% tissue culture infectious dose (TCID₅₀). (D) Quantitative PCR analysis of VSV RNA in the liver, spleen, lungs or HSV-1 DNA in the brain of HDAC3^fl/fl or HDAC3^fl/fl Lyz2-Cre mice after intraperitoneal injection of PBS or VSV (24 h) or HSV-1 (5 d) (as in A). (E) ELISA analysis of IFN-β (left) in the supernatant of HDAC3^fl/fl or HDAC3^fl/fl Lyz2-Cre bone marrow derived macrophages (BMDMs), infected with SeV, VSV, HSV-1, poly (I:C) and LPS. HDAC3-deficiency in BMDMs were confirmed by immunoblotting analysis (right). Data are representative of three independent experiments. Graphs show mean ± SD; **P < 0.01; ***P < 0.001 (Student’s t-test)