MMAE enhanced the antiviral effects of cGAMP in a STING-dependent manner <i>in vivo</i>.

Abstract

(A-G and H-J) WT and Stinggt/gt C57BL/6 mice (n = 10) were treated with PBS, cGAMP (30 μg/mice), MMAE (0.5 mg/kg), or cGAMP along with MMAE by intraperitoneal injection (i.p.) for 2 h. Then, the mice were infected intravenously with HSV-1-GFP at 2 × 108 pfu per WT mouse or at 1 × 107 pfu per Stinggt/gt mouse. (A-C and I) Body weight of mice were observed and recorded daily. (D-G, H and J) Six days after virus infection, three C57BL/6 mice (WT and Stinggt/gt) were randomly selected for subsequent experiments. The viral titers of mouse spleens were measured by qRT-PCR assay (n = 3 biological replicates) (D). Expressions of viral genes in spleens were measured by immunoblotting and qPCR analysis (n = 3) (E, F, and J). Expressions of IFNβ and ISGs in spleens were analyzed by qPCR analysis (n = 3) (G and H). (K-P) C57BL/6 mice (WT, n = 4) were infected intravenously with HSV-1 at 1 × 107 pfu per mouse. 16 hours later, the mice were treated with PBS, cGAMP (30 μg/mice), MMAE (0.5 mg/kg), or cGAMP along with MMAE by intraperitoneal injection (i.p.) for 3 days. The viral titers of mouse livers and spleens were measured by qRT-PCR assay (K and N). Expressions of viral genes in livers and spleens were qualified by immunoblotting and qPCR analysis (L, M, O and P). (TIF)</p