TY - JOUR
T1 - Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity
AU - Biswas, Sreya
AU - Rust, Lauren N.
AU - Wettengel, Jochen M.
AU - Yusova, Sofiya
AU - Fischer, Miranda
AU - Carson, Julien N.
AU - Johnson, Josie
AU - Wei, Lei
AU - Thode, Trason
AU - Kaadige, Mohan R.
AU - Sharma, Sunil
AU - Agbaria, Majd
AU - Bimber, Benjamin N.
AU - Tu, Thomas
AU - Protzer, Ulrike
AU - Ploss, Alexander
AU - Smedley, Jeremy V.
AU - Golomb, Gershon
AU - Sacha, Jonah B.
AU - Burwitz, Benjamin J.
N1 - Funding Information:
We would like to thank Skip Virgin, Christy Hebner, Florian Lempp, Andrea Cathcart, and the Vir Biotechnology Virology section for productive discussion pertaining to chronic HBV infection and model development. We would also like to thank Jake Estes and his lab for support in optimizing liver microscopy, and to thank all animal care and veterinary staff at the Oregon National Primate Research Center for their dedication and tireless efforts to ensure the ethical completion of our study. Funding was provided by Vir SRA-17-077 (BJB, JBS), the Burroughs Wellcome Fund Award 101539 (AP), and the National Institutes of Health R21 AI108401 (BJB), R01 AI144008 (BJB), R01 AI157612 (BJB), Health R01 AI129703 (JBS), R01 AI138797 (AP), R01 AI153236 (AP), P51 OD011092 (ONPRC).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-30593-0
DO - 10.1038/s41467-022-30593-0
M3 - Article
C2 - 35637225
AN - SCOPUS:85130895830
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2995
ER -