HCV modifies the expression of the ErbB ligands NRG1 and EGF in a Sp1-dependent manner

Background & aims The Hepatitis C Virus (HCV) is one of the leading causes for chronic liver disease worldwide. The fact that an infection with HCV remains asymptomatic over decades suggests that the virus is able to efficiently subvert antiviral immunity and to utilize the host cell infrastructure without affecting cell viability. As our group described previously, the growth factors EGF and NRG1 are both overexpressed in the presence of HCV, either interfering with chemokine expression or rearranging the ErbB receptor expression pattern. This project focuses on the mechanism by which the expression of growth factors is altered in HCV infected cells.

Methods Experiments were performed in Huh9-13 replicon or Huh7 control cells. Inhibitors were used and ErbB ligand expression was determined by rtPCR. Binding of the transcription factors Sp1 and STAT1 to the respective promoter region was determined by chromatin immunoprecipitation (ChIP).

Results Inhibitor experiments provided evidence for an important role of Sp1 and STAT1 in the regulation of both EGF and NRG1 transcription, especially in the presence of HCV. Consistently, enhanced Sp1 and STAT1 DNA binding to the respective promoter could be demonstrated in Huh9-13 replicon cells by ChIP.

Discussion It could be shown that the transcription factor Sp1 as well as STAT1 are involved in the HCV-dependent upregulation of both NRG1 and EGF. While Sp1 and STAT1 expression is not enhanced in the presence of HCV, its DNA binding capacity to EGF and NRG1 promoter is significantly increased in Huh9-13 replicon cells compared to control.

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022