Unraveling the complexity of hepatitis B virus: from molecular understanding to therapeutic strategy in 50 years

Abstract

Hepatitis B virus (HBV) is a well-known hepadnavirus with a double-stranded circular DNA genome. Although HBV was first described approximately 50 years ago, the precise mechanisms of HBV infection and effective therapeutic strategies remain unclear. Here, we focus on summarizing the complicated mechanisms of HBV replication and infection, as well as genomic factors and epigenetic regulation. Additionally, we discuss in vivo models of HBV, as well as diagnosis, prevention and therapeutic drugs for HBV. Together, the data in this 50-year review may provide new clues to elucidate molecular mechanisms of HBV pathogenesis and shed new light on the future HBV therapies.

Keywords: 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated; 5-LOX; 5-lipoxygenase; AFP; ALDH1; ALL; ALT; AR; AST; C/EBP-β; CCAAT enhancer binding protein β; CD8T lymphocytes; CDH1; CHB; CIITA; CP; CREB; CRHR2; CTLs; CXCR1; DDC; DTP; FAK; FDA; FXRA; Food and Drug Administration; HB; HBIG; HBV; HBV therapy; HBcAg; HBeAg; HBsAg; HBx; HBx protein; HCC; HDAC1; HO-1; Heme oxygenase-1; Hepatitis B virus; Hepatocellular carcinoma; IFN-α; IFNAR1; IL; In vivo model; JAK; Janus kinase; MAPK; MMF; MTA1; NHP; OPN; ORFs; PC; PEG; PH; PKC; PP1; PPIs; RNA interference; RNAi; SNPs; SPP1; STAT; TATA binding protein; TBP; TGF; TNF; WHV; alanine aminotransferase; aldehyde dehydrogenase 1; androgen receptor; aspartate aminotransferase; cadherin-1; cccDNA; chemokine (C-X-C motif) receptor 1; chronic hepatitis B; class II transactivator; core promoter; corticotropin-releasing hormone receptor 2; covalently closed circular DNA; cyclic adenosine monophosphate (cAMP) response element-binding protein; diphtheria–tetanus–pertussis; farnesoid X receptor alpha; focal adhesion kinase; hepatitis B; hepatitis B X protein; hepatitis B core antigen; hepatitis B e antigen; hepatitis B immune globulin; hepatitis B surface antigen; hepatitis B virus; hepatocellular carcinoma; heterogeneous nuclear ribonucleoproteins K; histone deacetylase 1; hnRNP K; interferon alpha; interleukin; lymphoblastic leukemia; macrophagic myofasciitis; metastasis-associated protein 1; miRNA; microRNA; mitogen-activated protein kinase; non-human primates; open reading frames; osteopontin; polyethylene glycol; portal hypertension; precore; protein kinase C; protein phosphatase 1; protein–protein interactions; secreted phosphoprotein-1; signal transducer and activator of transcription; single nucleotide polymorphisms; transforming growth factor; tumor necrosis factor; type I interferon (IFN-alpha/beta) receptor 1; woodchuck hepatitis virus; α-fetoprotein.