ArticleHepatology (Baltimore, Md.)2017
Sodium taurocholate cotransporting polypeptide is the limiting host factor of hepatitis B virus infection in macaque and pig hepatocytes.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 98 citations in OpenAlex.
- The Role of Human Viral Entry Receptor Mouse Models in Advancing Antiviral Antibodies and Vaccines.Vaccines · 2026Review
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- Hepatitis B virus covalently closed circular DNA formation in murine hepatic cells uncovers a late entry block.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Woodchuck and deer Hepatitis Delta-like agents show distinct innate immune activation and IFN-resistance compared to human Hepatitis D Virus.Scientific reports · 2026Article
- Multistep receptor binding of the hepatitis B virus preS1 domain.Nature communications · 2026Article
- Structural mapping of NTCP distinguishes its dual functionality as a hepatitis B virus receptor and bile acid transporter.PLoS pathogens · 2026Article
- NTCP ubiquitination enables HBV infection.JHEP reports : innovation in hepatology · 2025Article
- Screening of different species reveals cat hepatocytes support HBV infection.PLoS pathogens · 2025Article
- Hepatitis B and D virus entry.Nature reviews. Microbiology · 2025Review
- Identification of NTCP animal orthologs supporting hepatitis B virus binding and infection.Journal of virology · 2025Article
- Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases.Biomolecules · 2025Review
- Structural basis for hepatitis B virus restriction by a viral receptor homologue.Nature communications · 2024Article
- An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes.EMBO reports · 2024Article
- Article
- Progress of Infection and Replication Systems of Hepatitis B Virus.ACS pharmacology & translational science · 2024Review
- Organ-on-chip models for infectious disease research.Nature microbiology · 2024Review
- Hepatitis B virus-targeting sodium taurocholate cotransporting polypeptide mediates HBV infection and damage in human renal podocytes.Microbiology spectrum · 2024Article
- Trichinella spiralis -induced immunomodulation signatures on gut microbiota and metabolic pathways in mice.PLoS pathogens · 2024Article
- Aborted infection of human sodium taurocholate cotransporting polypeptide (hNTCP) expressing woodchuck hepatocytes with hepatitis B virus (HBV).Virus genes · 2023Article
- Vector-Mediated Delivery of Human Major Histocompatibility Complex-I into Hepatocytes Enables Investigation of T Cell Receptor-Redirected Hepatitis B Virus-Specific T Cells in Mice, and in Macaque Cell Cultures.Human gene therapy · 2023Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infections with the human hepatitis B virus (HBV) and hepatitis D virus (HDV) depend on species-specific host factors like the receptor human sodium taurocholate cotransporting polypeptide (hNTCP). Complementation of mouse hepatocytes with hNTCP confers susceptibility to HDV but not HBV, indicating the requirement of additional HBV-specific factors. As an essential premise toward the establishment of an HBV-susceptible animal model, we investigated the role of hNTCP as a limiting factor of hepatocytes in commonly used laboratory animals. Primary hepatocytes from mice, rats, dogs, pigs, rhesus macaques, and cynomolgus macaques were transduced with adeno-associated viral vectors encoding hNTCP and subsequently infected with HBV. Cells were analyzed for Myrcludex B binding, taurocholate uptake, HBV covalently closed circular DNA formation, and expression of all HBV markers. Sodium taurocholate cotransporting polypeptide (Ntcp) from the respective species was cloned and analyzed for HBV and HDV receptor activity in a permissive hepatoma cell line. Expression of hNTCP in mouse, rat, and dog hepatocytes permits HDV infection but does not allow establishment of HBV infection. Contrarily, hepatocytes from cynomolgus macaques, rhesus macaques, and pigs became fully susceptible to HBV upon hNTCP expression with efficiencies comparable to human hepatocytes. Analysis of cloned Ntcp from all species revealed a pronounced role of the human homologue to support HBV and HDV infection.
conclusionNtcp is the key host factor limiting HBV infection in cynomolgus and rhesus macaques and in pigs. In rodents (mouse, rat) and dogs, transfer of hNTCP supports viral entry but additional host factors are required for the establishment of HBV infection. This finding paves the way for the development of macaques and pigs as immunocompetent animal models to study HBV infection in vivo, immunological responses against the virus and viral pathogenesis. (Hepatology 2017;66:703-716).
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