Aborted infection of human sodium taurocholate cotransporting polypeptide (hNTCP) expressing woodchuck hepatocytes with hepatitis B virus (HBV).

Abstract

Due to the limited host range of HBV, research progress has been hindered by the absence of a suitable animal model. The natural history of woodchuck hepatitis virus (WHV) infection in woodchuck closely mirrors that of HBV infection in human, making this species a promising candidate for establishing both in vivo and in vitro HBV infection models. Therefore, this animal may be a valuable species to evaluate HBV vaccines and anti-HBV drugs. A significant milestone in HBV and hepatitis D virus (HDV) infection is the discovery of sodium taurocholate cotransporting polypeptide (NTCP) as the functional receptor. In an effort to enhance susceptibility to HBV infection, we introduced hNTCP into the woodchuck hepatocytes by multiple approaches including transduction of vLentivirus-hNTCP in woodchuck hepatocytes, transfection of p-lentivirus-hNTCP-eGFP plasmids into these cells, as well as transduction of vAdenovirus-hNTCP-eGFP. Encouragingly, our findings demonstrated the successful introduction of hNTCP into woodchuck hepatocytes. However, it was observed that these hNTCP-expressing hepatocytes were only susceptible to HDV infection but not HBV. This suggests the presence of additional crucial factors mediating early-stage HBV infection that are subject to stringent species-specific restrictions.

• Authors: Lu Yang, Di Zhou, Kächele Martin, Jun Wu, Mingfa Chen, Mengji Lu, Dongliang Yang, Ulrike Protzer, Michael Roggendorf, Jingjiao Song
• Journal: Virus genes (Virus Genes) Vol. 59 Issue 6 Pg. 823-830 (Dec 2023) ISSN: 1572-994X [Electronic] United States
• PMID: 37728707 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• sodium-bile acid cotransporter
• Organic Anion Transporters, Sodium-Dependent

Topics

• Animals
• Humans
• Hepatitis B virus (genetics)
• Marmota
• Hepatocytes
• Organic Anion Transporters, Sodium-Dependent (genetics)
• Hepatitis B
• Hepatitis D
• Hepatitis Delta Virus (genetics)
• Virus Internalization