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Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity

Author

Listed:
  • Sreya Biswas

    (Oregon Health & Science University)

  • Lauren N. Rust

    (Oregon Health & Science University)

  • Jochen M. Wettengel

    (Oregon Health & Science University
    Technical University of Munich / Helmholtz Zentrum München)

  • Sofiya Yusova

    (Oregon Health & Science University)

  • Miranda Fischer

    (Oregon Health & Science University)

  • Julien N. Carson

    (Oregon Health & Science University)

  • Josie Johnson

    (Oregon Health & Science University)

  • Lei Wei

    (Princeton University)

  • Trason Thode

    (Translational Genomics Research Institute)

  • Mohan R. Kaadige

    (Translational Genomics Research Institute)

  • Sunil Sharma

    (Translational Genomics Research Institute)

  • Majd Agbaria

    (The Hebrew University of Jerusalem)

  • Benjamin N. Bimber

    (Oregon Health & Science University)

  • Thomas Tu

    (The University of Sydney
    University of Sydney at Westmead Hospital)

  • Ulrike Protzer

    (Technical University of Munich / Helmholtz Zentrum München)

  • Alexander Ploss

    (Princeton University)

  • Jeremy V. Smedley

    (Oregon Health & Science University)

  • Gershon Golomb

    (The Hebrew University of Jerusalem)

  • Jonah B. Sacha

    (Oregon Health & Science University
    Oregon Health & Science University)

  • Benjamin J. Burwitz

    (Oregon Health & Science University
    Oregon Health & Science University)

Abstract

Hepatitis B virus has infected a third of the world’s population, and 296 million people are living with chronic infection. Chronic infection leads to progressive liver disease, including hepatocellular carcinoma and liver failure, and there remains no reliable curative therapy. These gaps in our understanding are due, in large part, to a paucity of animal models of HBV infection. Here, we show that rhesus macaques regularly clear acute HBV infection, similar to adult humans, but can develop long-term infection if immunosuppressed. Similar to patients, we longitudinally detected HBV DNA, HBV surface antigen, and HBV e antigen in the serum of experimentally infected animals. In addition, we discovered hallmarks of HBV infection in the liver, including RNA transcription, HBV core and HBV surface antigen translation, and covalently closed circular DNA biogenesis. This pre-clinical animal model will serve to accelerate emerging HBV curative therapies into the clinic.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30593-0
    DOI: 10.1038/s41467-022-30593-0
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    References listed on IDEAS

    as
    1. Benjamin J. Burwitz & Helen L. Wu & Shaheed Abdulhaqq & Christine Shriver-Munsch & Tonya Swanson & Alfred W. Legasse & Katherine B. Hammond & Stephanie L. Junell & Jason S. Reed & Benjamin N. Bimber &, 2017. "Allogeneic stem cell transplantation in fully MHC-matched Mauritian cynomolgus macaques recapitulates diverse human clinical outcomes," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    2. Masahito Tachibana & Michelle Sparman & Hathaitip Sritanaudomchai & Hong Ma & Lisa Clepper & Joy Woodward & Ying Li & Cathy Ramsey & Olena Kolotushkina & Shoukhrat Mitalipov, 2009. "Mitochondrial gene replacement in primate offspring and embryonic stem cells," Nature, Nature, vol. 461(7262), pages 367-372, September.
    3. 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.
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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.

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