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

doi:10.1038/s41467-022-30593-0

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

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13 Scopus citations

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 language	English (US)
Article number	2995
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-30593-0
State	Published - Dec 2022

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Biswas, S., Rust, L. N., Wettengel, J. M., Yusova, S., Fischer, M., Carson, J. N., Johnson, J., Wei, L., Thode, T., Kaadige, M. R., Sharma, S., Agbaria, M., Bimber, B. N., Tu, T., Protzer, U., Ploss, A., Smedley, J. V., Golomb, G., Sacha, J. B., & Burwitz, B. J. (2022). Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity. Nature communications, 13(1), Article 2995. https://doi.org/10.1038/s41467-022-30593-0

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title = "Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity",

abstract = "Hepatitis B virus has infected a third of the world{\textquoteright}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.",

author = "Sreya Biswas and Rust, {Lauren N.} and Wettengel, {Jochen M.} and Sofiya Yusova and Miranda Fischer and Carson, {Julien N.} and Josie Johnson and Lei Wei and Trason Thode and Kaadige, {Mohan R.} and Sunil Sharma and Majd Agbaria and Bimber, {Benjamin N.} and Thomas Tu and Ulrike Protzer and Alexander Ploss and Smedley, {Jeremy V.} and Gershon Golomb and Sacha, {Jonah B.} and Burwitz, {Benjamin J.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-30593-0",

language = "English (US)",

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Biswas, S, Rust, LN, Wettengel, JM, Yusova, S, Fischer, M, Carson, JN, Johnson, J, Wei, L, Thode, T, Kaadige, MR, Sharma, S, Agbaria, M, Bimber, BN, Tu, T, Protzer, U, Ploss, A, Smedley, JV, Golomb, G, Sacha, JB & Burwitz, BJ 2022, 'Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity', Nature communications, vol. 13, no. 1, 2995. https://doi.org/10.1038/s41467-022-30593-0

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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.

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

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