Genome-Wide Transcriptome Analysis of CD36 Overexpression in HepG2.2.15 Cells to Explore Its Regulatory Role in Metabolism and the Hepatitis B Virus Life Cycle

PLoS One. 2016 Oct 17;11(10):e0164787. doi: 10.1371/journal.pone.0164787. eCollection 2016.


Hepatitis B virus (HBV) is a hepatocyte-specific DNA virus whose gene expression and replication are closely associated with hepatic metabolic processes. Thus, a potential anti-viral strategy is to target the host metabolic factors necessary for HBV gene expression and replication. Recent studies revealed that fatty acid translocase CD36 is involved in the replication, assembly, storage, and secretion of certain viruses, such as hepatitis C virus (HCV) and human immunodeficiency virus (HIV). However, the relationship between CD36 and the HBV life cycle remains unclear. Here, we showed, for the first time, that increased CD36 expression enhances HBV replication in HepG2.2.15 cells. To understand the underlying molecular basis, we performed genome-wide sequencing of the mRNA from HepG2.2.15-CD36 overexpression (CD36OE) cells and HepG2.2.15-vector cells using RNA Sequencing (RNA-seq) technology to analyze the differential transcriptomic profile. Our results identified 141 differentially expressed genes (DEGs) related to CD36 overexpression, including 79 upregulated genes and 62 downregulated genes. Gene ontology and KEGG pathway analysis revealed that some of the DEGs were involved in various metabolic processes and the HBV life cycle. The reliability of the RNA-Seq data was confirmed by qPCR analysis. Our findings provide clues to build a link between CD36, host metabolism and the HBV life cycle and identified areas that require further investigation.

MeSH terms

  • CD36 Antigens / genetics
  • CD36 Antigens / metabolism*
  • Down-Regulation
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Genome, Human
  • Hep G2 Cells
  • Hepatitis B virus / physiology*
  • Humans
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Transcriptome
  • Up-Regulation
  • Virus Replication / physiology*


  • CD36 Antigens
  • RNA, Messenger

Grants and funding

This work was supported by National Natural Science Foundation of China (81570517),, YXC received the funding; National Natural Science Foundation of China (81270789, 81390354),, XZR received the funding; Chongqing Research Program of Basic Research and Frontier Technology (No. cstc2015jcyjBX0044),, YXC received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.