Small hepatitis delta antigen selectively binds to target mRNA in hepatic cells: a potential mechanism by which hepatitis D virus downregulates glutathione S-transferase P1 and induces liver injury and hepatocarcinogenesis

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
Mianzhi ChenMeng Gong

Abstract

Liver coinfection by hepatitis B virus (HBV) and hepatitis D virus (HDV) can result in a severe form of hepatocellular carcinoma with poor prognosis. Coinfection with HDV and HBV causes more deleterious effects than infection with HBV alone. Clinical research has shown that glutathione S-transferase P1 (GSTP1), a tumor suppressor gene, is typically downregulated in liver samples from hepatitis-infected patients. In the present study, our data indicated that small HDV antigen (s-HDAg) could specifically bind to GSTP1 mRNA and significantly downregulate GSTP1 protein expression. For the human fetal hepatocyte cell line L-02, cells transfected with s-HDAg, along with decreased GSTP1 expression, there was a significant accumulation of reactive oxygen species (ROS) and increased apoptotic ratios. Restoring GSTP1 expression through silencing s-HDAg via RNAi or overexpressing exogenous GSTP1 could largely recover the abnormal cell status. Our results revealed a novel potential mechanism of HDV-induced liver injury and hepatocarcinogenesis: s-HDAg can inhibit GSTP1 expression by directly binding to GSTP1 mRNA, which leads to accumulation of cellular ROS, resulting in high cellular apoptotic ratios and increased selective pressure for m...Continue Reading

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Citations

Nov 3, 2020·World Journal of Gastroenterology : WJG·Simmone D'souzaTrushar R Patel
May 4, 2020·Antiviral Research·Julie Lucifora, Marion Delphin
Apr 2, 2021·Reviews in Medical Virology·Sonia Romero-CorderoConstanza Morén
May 1, 2021·Viruses·Eirini D TseligkaFrancesco Negro
Jun 3, 2021·Viruses·Patrizia FarciGiacomo Diaz
Dec 1, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Peter SchemmerDidier Samuel

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