Fig. 3: HBV induced transcriptional changes in host cells with SIRT6 emerging as a potential host virus-restricting factor. | Cell Discovery

Fig. 3: HBV induced transcriptional changes in host cells with SIRT6 emerging as a potential host virus-restricting factor.

From: Multiomics interrogation into HBV (Hepatitis B virus)-host interaction reveals novel coding potential in human genome, and identifies canonical and non-canonical proteins as host restriction factors against HBV

Fig. 3

a RNA-sequencing was conducted with Huh7.5.1 cells transfected with Vector (Control) or prcccDNA and pCMV-Cre. Heatmap of 11 transcriptional DEGs, which have transcription corepressor activity, three biological replicates were shown for HBV and control group. b RT-qPCR confirmed that HBV downregulated the transcriptional level of endogenous SIRT6 transcription. c Network analysis of SIRT6-associated genes whose transcription was altered by HBV. Red and blue nodes indicate the upregulated and downregulated genes, respectively. The color intensity indicates the fold change level of the gene. Nodes with * are DEGs (P-adjust <0.05, |log2FC| ≥ 1, also see methods). d RT-qPCR validation of some of the SIRT6-associated genes that were shown in c. e Representative profiles of ribosome footprints of human SIRT6 ORF upon HBV, translation initiation of endogenous SIRT6 was downregulated by HBV in Huh7.5.1 cells. The highest read count was set as 1 and the read counts of other groups were normalized to this group. f Endogenous SIRT6 was downregulated by HBV in Huh7.5.1 cells. g De novo infection of HBV downregulated endogenous SIRT6 level in HepG2-NTCP cells, HepG2 cells stably expressing NTCP (sodium taurocholate cotransporting polypeptide), the functional receptor of HBV. The results of two independent biological replicates were shown. h HBV downregulated SIRT6 in mouse livers infected with adenovirus harboring HBV genome. i Total proteins were extracted from the normal liver tissues of 12 patients who were diagnosed with HBV positive and negative, respectively. For patient information see Supplementary Table S1. Endogenous SIRT6 or GAPDH proteins were visualized with IB using anti-SIRT6 or anti-GAPDH, with their relative abundances calculated using ImageJ. j The reverse correlation between the serum levels of HBsAg and the relative abundances of endogenous SIRT6 protein in liver tissues of the 12 patients. *P < 0.05, **P < 0.01, ***P < 0.001. qPCR results are presented as bar chart (For SIRT6, n = 2; for other genes, n = 3); ELISA data are presented as bar chart (n = 3).

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