Fig. 1

HCMV US7 and US8 target TLR3-mediated and TLR4-mediated antiviral responses. a Schematic representation of the HCMV genome and the US2-US11 region capable of targeting various cellular immune molecules. b Heat map showing expression of cellular targets of US7 and US8 in HFF cells expressing US7 or US8 after stimulation by dsDNA (Supplementary Data 1). c Change in cellular mRNA expression caused by US7 or US8 versus mRNA expression in empty vector-expressing HFF cells stimulated by dsDNA. Scatter plots of US7- or US8-upregulated ( > 1.5-fold change, red dots) or -downregulated genes ( < 1.5-fold change, blue dots) in dsDNA-stimulated HFF cells. d US7 and US8 inhibit DNA-induced innate antiviral response. HFF cells expressing empty vector, HA-US7, or HA-US8 were transfected with 500 ng ml⁻¹ dsDNA for 12 h. The mRNA expression of the indicated genes was analyzed by qPCR or RT-PCR. *P < 0.001, **P < 0.05 (Student’s t-test). e US7 and US8 inhibit antiviral gene expression mediated by TLR3 and TLR4. TLR3-Myc- or TLR4-Myc-expressing HFF cells were transduced with empty vector, HA-US7, or HA-US8 and were then stimulated by 10 μg ml⁻¹ poly(I:C) or 5 μg ml⁻¹ LPS for 12 h. The indicated gene expression was measured by qPCR. *P < 0.001, **P < 0.05 (Student’s t-test) f US7 and US8 suppress ifnb and nfkb promoter activity. Luciferase assays of ifnb and nfkb promoter activity in TLR3- or TLR4/MD2-expressing HEK293T cells transfected with empty vector, HA-US7, or HA-US8 and incubated with 5 μg ml⁻¹ LPS or 10 μg ml⁻¹ poly(I:C) for 12 h. The protein over-expression of HA-US7 or HA-US8 was analyzed by immunoblot analysis with anti-HA antibody. *P < 0.001, **P < 0.05 (Student’s t-test). g US7 and US8 block IFN-β production mediated by TLR3 and TLR4. THP-1 cells expressing empty vector, US7, or US8 were stimulated by 100 μg ml⁻¹ poly(I:C) or 1 μg ml⁻¹ LPS for 24 h. IFN-β secretion levels or HA-US7/US8 overexpression levels were analyzed by ELISA or immunoblot analysis, respectively. *P < 0.001, **P < 0.05 (Student’s t-test). Data are representative of three independent experiments and are presented as the mean ± s.d. in d–g. Source data are provided as a Source Data file