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

Author

Listed:
  • Benjamin J. Burwitz

    (Vaccine and Gene Therapy Institute, Oregon Health and Science University)

  • Jochen M. Wettengel

    (Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich)

  • Martin A. Mück-Häusl

    (Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich)

  • Marc Ringelhan

    (Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich
    Klinikum rechts der Isar Technical University of Munich)

  • Chunkyu Ko

    (Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich)

  • Marvin M. Festag

    (Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich)

  • Katherine B. Hammond

    (Vaccine and Gene Therapy Institute, Oregon Health and Science University)

  • Mina Northrup

    (Vaccine and Gene Therapy Institute, Oregon Health and Science University)

  • Benjamin N. Bimber

    (Oregon National Primate Research Center, Oregon Health and Science University)

  • Thomas Jacob

    (Oregon Health and Science University)

  • Jason S. Reed

    (Vaccine and Gene Therapy Institute, Oregon Health and Science University)

  • Reed Norris

    (Oregon National Primate Research Center, Oregon Health and Science University)

  • Byung Park

    (Public Health and Preventative Medicine, Oregon Health and Science University)

  • Sven Moller-Tank

    (The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill)

  • Knud Esser

    (Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich)

  • Justin M. Greene

    (Vaccine and Gene Therapy Institute, Oregon Health and Science University)

  • Helen L. Wu

    (Vaccine and Gene Therapy Institute, Oregon Health and Science University)

  • Shaheed Abdulhaqq

    (Vaccine and Gene Therapy Institute, Oregon Health and Science University)

  • Gabriela Webb

    (Vaccine and Gene Therapy Institute, Oregon Health and Science University)

  • William F. Sutton

    (Oregon National Primate Research Center, Oregon Health and Science University)

  • Alex Klug

    (Oregon National Primate Research Center, Oregon Health and Science University)

  • Tonya Swanson

    (Oregon National Primate Research Center, Oregon Health and Science University)

  • Alfred W. Legasse

    (Oregon National Primate Research Center, Oregon Health and Science University)

  • Tania Q. Vu

    (Oregon Health and Science University
    Center for Spatial Systems Bioscience, Oregon Health and Science University)

  • Aravind Asokan

    (The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill
    The University of North Carolina at Chapel Hill)

  • Nancy L. Haigwood

    (Oregon National Primate Research Center, Oregon Health and Science University)

  • Ulrike Protzer

    (Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich
    German Center for Infection Research, Munich partner site)

  • Jonah B. Sacha

    (Vaccine and Gene Therapy Institute, Oregon Health and Science University
    Oregon National Primate Research Center, Oregon Health and Science University)

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.

Suggested Citation

  • 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. , 2017. "Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01953-y
    DOI: 10.1038/s41467-017-01953-y
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    Cited by:

    1. Yongzhen Liu & Thomas R. Cafiero & Debby Park & Abhishek Biswas & Benjamin Y. Winer & Cheul H. Cho & Yaron Bram & Vasuretha Chandar & Aoife K. O’ Connell & Hans P. Gertje & Nicholas Crossland & Robert, 2023. "Targeted viral adaptation generates a simian-tropic hepatitis B virus that infects marmoset cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Sreya Biswas & Lauren N. Rust & Jochen M. Wettengel & Sofiya Yusova & Miranda Fischer & Julien N. Carson & Josie Johnson & Lei Wei & Trason Thode & Mohan R. Kaadige & Sunil Sharma & Majd Agbaria & Ben, 2022. "Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Kaho Shionoya & Jae-Hyun Park & Toru Ekimoto & Junko S. Takeuchi & Junki Mifune & Takeshi Morita & Naito Ishimoto & Haruka Umezawa & Kenichiro Yamamoto & Chisa Kobayashi & Atsuto Kusunoki & Norimichi , 2024. "Structural basis for hepatitis B virus restriction by a viral receptor homologue," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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