DNA methyltransferases 1 and 3B are required for hepatitis C virus infection in cell culture

Abstract

DNA methyltransferases (DNMTs) are responsible for establishing and maintaining DNA methylation, which are dysregulated in hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). In this report, using lentivirus-mediated shRNA interference technology, we identified DNMT1 and DNMT3B as host factors involved in HCV propagation. Our results demonstrated that down-regulation of DNMT1 or DNMT3B expression in Huh7.5.1 cells severely impaired cell culture-produced HCV (HCVcc) infection. Furthermore, knockdown of DNMT1 or DNMT3B did not affect HCV entry and internal ribosome entry site (IRES)-directed translation but did inhibit subgenomic replication. In contrast, knockdown of DNMT3A had no significant effect on HCV infection, entry, translation, or replication, which suggested that DNMT3A did not play a significant role in HCV life cycle. Moreover, we showed that DNMT inhibitors 5-Aza-C and 5-Aza-dC significantly suppressed HCVcc infection, viral RNA replication, and protein expression. These results suggest that DNMTs are critical for HCV replication and may represent potent targets for the treatment of HCV infection.

Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity

“…Dnmt3a acts as a host factor required for effective HSV-1 infection 37 , and Dnmt1 and Dnmt3b are required for the propagation of hepatitis C virus 38 . DNA methyltransferases also methylate viral DNA, which leads to decreased infection with hepatitis B virus 39 .…”

Gene-gene and gene-sex epistatic interactions of <i>DNMT1</i>, <i>DNMT3A</i> and <i>DNMT3B</i> in autoimmune thyroid disease

“…It is reported that down-regulation of DNMT1 or DNMT3B expression in Huh7.5.1 cells severely impaired cell culture-produced HCV infection. DNMTs are critical for HCV replication and may represent potent targets for the treatment of HCV infection [31]. Therefore, our observation might raise the possibility of various immune mechanisms such as DNMT1 polymorphisms might affect the susceptibility of HCV and AITD.…”

Hepatitis C virus core protein inhibits E6AP expression via DNA methylation to escape from ubiquitin-dependent proteasomal degradation

“…Recently, Chen et al have demonstrated that DNA methylation is required for HCV infection in cell culture [52]. According to this report, inhibition of DNA methylation by either treatment with DNMT inhibitors or knock-down of DNMT1 and 3b significantly suppresses HCV infection, viral RNA replication, and protein expression.…”