Human apolipoprotein E promotes hepatitis B virus infection and production

• Published in: PLoS pathogens 2019-08, Vol.15 (8), p.e1007874-e1007874
• Main Authors: Qiao, Luhua, Luo, Guangxiang George
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Analysis; Antibodies; Antiviral agents; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - antagonists & inhibitors; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Binding sites; Biology and life sciences; Biosynthesis; Broadway theater; Carcinoma; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Cell culture; Chronic infection; Cirrhosis; Control; CRISPR; Deoxyribonucleic acid; Development and progression; DNA; DNA biosynthesis; DNA polymerase; DNA replication; Drugs; Fibrosis; Gene expression; Genes; Genomes; Global health; Health; Health aspects; Hep G2 Cells; Heparan sulfate; Hepatitis; Hepatitis B; Hepatitis B - complications; Hepatitis B - virology; Hepatitis B Antibodies - immunology; Hepatitis B virus; Hepatitis B virus - immunology; Hepatitis B virus - pathogenicity; Hepatitis C; Hepatitis C virus; Hepatocellular carcinoma; Humans; Immune response; Immune system; Infection; Infections; Infectivity; Life cycles; Lipids; Liver cirrhosis; Liver diseases; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - virology; Low density lipoprotein receptors; Medical research; Medicine and health sciences; Metabolism; Monoclonal antibodies; Morphogenesis; Nucleocapsids; Pathogenesis; Proteins; Receptors; Reduction; Replication; Research and Analysis Methods; RNA, Small Interfering - genetics; Steatosis; Virus diseases; Virus Replication; Viruses; World health
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007874

Hepatitis B virus (HBV) is a common cause of liver diseases, including chronic hepatitis, steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HBV chronically infects about 240 million people worldwide, posing a major global health problem. The current standard antiviral therapy effectively inhibits HBV replication but does not eliminate the virus unlike direct-acting antivirals (DAA) for curing hepatitis C. Our previous studies have demonstrated that human apolipoprotein E (apoE) plays important roles in hepatitis C virus infection and morphogenesis. In the present study, we have found that apoE is also associated with HBV and is required for efficient HBV infection. An apoE-specific monoclonal antibody was able to capture HBV similar to anti-HBs. More importantly, apoE monoclonal antibody could effectively block HBV infection, resulting in a greater than 90% reduction of HBV infectivity. Likewise, silencing of apoE expression or knockout of apoE gene by CRISPR/Cas9 resulted in a greater than 90% reduction of HBV infection and more than 80% decrease of HBV production, which could be fully restored by ectopic apoE expression. However, apoE silencing or knockout did not significantly affect HBV DNA replication or the production of nonenveloped (naked) nucleocapsids. These findings demonstrate that human apoE promotes HBV infection and production. We speculate that apoE may also play a role in persistent HBV infection by evading host immune response similar to its role in the HCV life cycle and pathogenesis. Inhibitors interfering with apoE biogenesis, secretion, and/or binding to receptors may serve as antivirals for elimination of chronic HBV infection.