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Nat Commun. 2017 Dec 15;8(1):2146. doi: 10.1038/s41467-017-01953-y.

Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques.

Author information

1
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA. burwitz@ohsu.edu.
2
Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich, Munich, 81675, Germany.
3
Department of Internal Medicine II, Klinikum rechts der Isar Technical University of Munich, Munich, 81675, Germany.
4
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.
5
Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, 97006, USA.
6
Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, 97239, USA.
7
Public Health and Preventative Medicine, Oregon Health and Science University, Portland, OR, 97239, USA.
8
Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
9
Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
10
Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
11
Center for Spatial Systems Bioscience, Oregon Health and Science University, Portland, OR, 97201, USA.
12
German Center for Infection Research, Munich partner site, Munich, 81675, Germany.

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.

PMID:
29247188
PMCID:
PMC5732258
DOI:
10.1038/s41467-017-01953-y
[Indexed for MEDLINE]
Free PMC Article

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