Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques /631/326/596/1550 /631/326/596/2555 /631/326/596/2557 article

Benjamin J. Burwitz, Jochen M. Wettengel, Martin A. Mück-Häusl, Marc Ringelhan, Chunkyu Ko, Marvin M. Festag, Katherine B. Hammond, Mina Northrup, Benjamin N. Bimber, Thomas Jacob, Jason S. Reed, Reed Norris, Byung Park, Sven Moller-Tank, Knud Esser, Justin M. Greene, Helen L. Wu, Shaheed Abdulhaqq, Gabriela Webb, William F. SuttonAlex Klug, Tonya Swanson, Alfred W. Legasse, Tania Q. Vu, Aravind Asokan, Nancy L. Haigwood, Ulrike Protzer, Jonah B. Sacha

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present. Furthermore, viral vector-mediated expression of hNTCP on hepatocytes in vivo renders rhesus macaques permissive to HBV infection. These in vivo macaque HBV infections are characterized by longitudinal HBV DNA in serum, and detection of HBV DNA, RNA, and HBV core antigen (HBcAg) in hepatocytes. Together, these results show that expressing hNTCP on macaque hepatocytes renders them susceptible to HBV infection, thereby establishing a physiologically relevant model of HBV infection to study immune clearance and test therapeutic and curative approaches.

Original languageEnglish (US)
Article number2146
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques /631/326/596/1550 /631/326/596/2555 /631/326/596/2557 article'. Together they form a unique fingerprint.

  • Cite this

    Burwitz, B. J., Wettengel, J. M., Mück-Häusl, M. A., Ringelhan, M., Ko, C., Festag, M. M., Hammond, K. B., Northrup, M., Bimber, B. N., Jacob, T., Reed, J. S., Norris, R., Park, B., Moller-Tank, S., Esser, K., Greene, J. M., Wu, H. L., Abdulhaqq, S., Webb, G., ... Sacha, J. B. (2017). Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques /631/326/596/1550 /631/326/596/2555 /631/326/596/2557 article. Nature communications, 8(1), [2146]. https://doi.org/10.1038/s41467-017-01953-y