Journal Article

Human low-density lipoprotein receptor plays an important role in hepatitis B virus infection

Li, Yingying, Luo, Guangxiang

2021

Overview

Hepatitis B virus (HBV) chronically infects more than 240 million people worldwide, resulting in chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV vaccine is effective to prevent new HBV infection but does not offer therapeutic benefit to hepatitis B patients. Neither are current antiviral drugs curative of chronic hepatitis B. A more thorough understanding of HBV infection and replication holds a great promise for identification of novel antiviral drugs and design of optimal strategies towards the ultimate elimination of chronic hepatitis B. Recently, we have developed a robust HBV cell culture system and discovered that human apolipoprotein E (apoE) is enriched on the HBV envelope and promotes HBV infection and production. In the present study, we have determined the role of the low-density lipoprotein receptor (LDLR) in HBV infection. A LDLR-blocking monoclonal antibody potently inhibited HBV infection in HepG2 cells expressing the sodium taurocholate cotransporting polypeptide (NTCP) as well as in primary human hepatocytes. More importantly, small interfering RNAs (siRNAs)-mediated knockdown of LDLR expression and the CRISPR/Cas9-induced knockout of the LDLR gene markedly reduced HBV infection. A recombinant LDLR protein could block heparin-mediated apoE pulldown, suggesting that LDLR may act as an HBV cell attachment receptor via binding to the HBV-associated apoE. Collectively, these findings demonstrate that LDLR plays an important role in HBV infection probably by serving as a virus attachment receptor.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Antiviral agents / Antiviral drugs / Apolipoprotein E / Biology and life sciences / Blocking / Cancer / Cell adhesion / Cell culture / Cells, Cultured / Chronic infection / Cirrhosis / CRISPR / Density / Development and progression / Drug development / Drugs / Enzymes / Genetic aspects / Health aspects / Heparan sulfate / Heparin / Hepatitis / Hepatitis B / Hepatitis B - virology / Hepatitis B virus - metabolism / Hepatitis C / Hepatocellular carcinoma / Hepatocytes / Hepatocytes - virology / Humans / Infections / LDLR gene / LDLR protein / Liver cancer / Liver cirrhosis / Low density lipoprotein receptors / Medicine and health sciences / Monoclonal antibodies / Morphogenesis / Polypeptides / Proteins / Receptor density / Receptors / Receptors, LDL - metabolism / Receptors, Virus - metabolism / Research and Analysis Methods / siRNA / Vaccines / Virus Attachment / Virus Internalization / Viruses