Innovative HBV Animal Models Based on the Entry Receptor NTCP

Hepatitis B is a major global health problem, with an estimated 257 million chronically infected patients and almost 1 million deaths per year. The causative agent is hepatitis B virus (HBV), a small, enveloped, partially double-stranded DNA virus. HBV has a strict species specificity, naturally infecting only humans and chimpanzees. Sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter expressed on hepatocytes, has been shown to be one of the key factors in HBV infection, playing a crucial role in the HBV entry process in vitro and in vivo. Variations in the amino acid sequence of NTCP can inhibit HBV infection and, therefore, contributes, in part, to the species barrier. This discovery has revolutionized the search for novel animal models of HBV. Indeed, it was recently shown that variations in the amino acid sequence of NTCP represent the sole species barrier for HBV infection in macaques. Here, we review what is known about HBV entry through the NTCP receptor and highlight how this knowledge has been harnessed to build new animal models for the study of HBV pathogenesis and curative therapies.