Role of HBV Replication in Host Cell Metabolism: A Proteomics Analysis

Laleh      Sadrolodabaee; Tiong   Keng   Low; Huixing      Feng; Wei   Ning   Chen

Abstract

Hepatocellular carcinoma (HCC) with more than 700,000 deaths every year is the most prevalent type of liver cancer and a global concern. It is the fifth most common cancer worldwide and has a poor general prognosis. Chronic hepatitis B virus (HBV) infection is a major cause of HCC. The HBV-infected individual has 100 times higher risk of developing HCC. The x protein of HBV (HBx) has been shown to involve in the development of HCC. In this study, the association between HBV replication and the host cell metabolism is investigated. HepG2 cells are transfected with different genotypes of HBx and total proteins are extracted and analyzed using LC-MS/MS. Our proteomics results indicates that a number of glycolytic enzymes including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), Phosphoglyceratekinase (PGK) and Lactate dehydrogenase (LDH) are significantly up-regulated in HepG2 cells transfected by HBx comparing with control group. These findings suggest that HBV replication could alter host cell metabolism by increasing the rate of glycolysis to provide important metabolic requirements for nucleotides, amino acids and lipids synthesis. Hence, our proteomics approach may provide candidate biomarkers to improve the diagnosis of HBVrelated HCC patients.

Keywords: Biomarker, HBV, HBx, HCC, LC-MS/MS, metabolic enzymes, proteomics.

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