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

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, Benjamin N. Bimber, Thomas Tu, Ulrike Protzer, Alexander Ploss, Jeremy V. Smedley, Gershon Golomb, Jonah B. Sacha, Benjamin J. Burwitz

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number2995
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

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

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