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

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 un...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2022-05, Vol.13 (1), p.2995-2995, Article 2995
Main Authors: Biswas, Sreya, Rust, Lauren N., Wettengel, Jochen M., Yusova, Sofiya, Fischer, Miranda, Carson, Julien N., Johnson, Josie, Wei, Lei, Thode, Trason, Kaadige, Mohan R., Sharma, Sunil, Agbaria, Majd, Bimber, Benjamin N., Tu, Thomas, Protzer, Ulrike, Ploss, Alexander, Smedley, Jeremy V., Golomb, Gershon, Sacha, Jonah B., Burwitz, Benjamin J.
Format: Article
Language:English
Subjects:
13
13/31
14
14/32
14/63
42
42/44
631/250/255/2514
631/326/596/1550
64
Animal models
Animals
Antigens
Antigens, Surface
Chronic infection
Circular DNA
Deoxyribonucleic acid
DNA
Hepatitis
Hepatitis B
Hepatitis B virus - genetics
Hepatitis B, Chronic
Hepatocellular carcinoma
Humanities and Social Sciences
Humans
Immunity
Infections
Liver
Liver diseases
Liver Neoplasms
Macaca mulatta
multidisciplinary
Science
Science (multidisciplinary)
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Here, Biswas et al . present and characterize a second-generation model of HBV infection in rhesus macaques, showing that extended infection requires suppression of host immunity.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-30593-0