Aborted infection of HBV in human sodium taurocholate cotransporting polypeptide (hNTCP) expressed woodchuck cells

Abstract

Abstract Hepatitis B virus (HBV) is a major healthy problem worldwide. Because of the narrow host range of HBV, relative research was hampered by lacking of an appropriate animal model. The natural history of woodchuck hepatitis virus (WHV) infection in woodchuck is highly similar to that of HBV infection in human. Therefore this animal may be an valuable species for establishing an in vivo and in vitro HBV infection model to evaluate HBV DNA vaccines and anti-HBV drugs. Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for HBV and hepatitis D virus (HDV) infection. Considering that HBV cannot successfully infect woodchuck cells possibly due to the difference of the functional domain between woodchuck NTCP (wNTCP) and human NTCP (hNTCP), therefore, we tried to make woodchuck hepatocytes susceptible to HBV infection by replacing wNTCP with hNTCP. In this study, hNTCP was introduced into the woodchuck hepatocytes by different approaches including transduction of vLentivirus-hNTCP in woodchuck hepatocytes, transfection of plentivirus-hNTCP-eGFP plasmids in woodchuck hepatocytes, as well as transduction of vAdenovirus-hNTCP-eGFP in woodchuck hepatocytes, in an attempt to make the woodchuck hepatocytes susceptible to HBV. The results showed that hNTCP was successfully introduced to the woodchuck hepatocytes. However, hNTCP-expressed woodchuck hepatocytes only sensitive to HDV infection but not HBV. This study indicating that there exist some other key factors mediate the HBV infection at early stage which have strict species specificity, and hNTCP is not the only determinant needed for HBV successful infection.