Abstract
AbstractHepatitis B virus (HBV) only infects humans and chimpanzees, posing major challenges for modeling HBV infection and chronic viral hepatitis. The major barrier in establishing HBV infection in non-human primates lies at incompatibilities between HBV and simian orthologues of the HBV receptor, sodium taurocholate co-transporting polypeptide (NTCP). Through mutagenesis analysis and screening among NTCP orthologues from Old World monkeys, New World monkeys and prosimians, we determined key residues responsible for viral binding and internalization, respectively and identified marmosets as a suitable candidate for HBV infection. Primary marmoset hepatocytes and induced pluripotent stem cell-derived hepatocyte-like cells support HBV and more efficient woolly monkey HBV (WMHBV) infection. Adapted chimeric HBV genome harboring residues 1–48 of WMHBV preS1 generated here led to a more efficient infection than wild-type HBV in primary and stem cell derived marmoset hepatocytes. Collectively, our data demonstrate that minimal targeted simianization of HBV can break the species barrier in small NHPs, paving the path for an HBV primate model.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
Burroughs Wellcome Fund
Princeton University
U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference61 articles.
1. Lang, J., Neumann-Haefelin, C. & Thimme, R. Immunological cure of HBV infection. Hepatol. Int. 13, 113–124 (2019).
2. Yuen, M. F. et al. Hepatitis B virus infection. Nat. Rev. Dis. Prim. 4, 18035 (2018).
3. Polaris Observatory, C. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol. Hepatol. 3, 383–403 (2018).
4. European Association for the Study of the Liver. Electronic address, e. e. e. & European Association for the Study of the, L. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol. 67, 370–398 (2017).
5. NIH. NIH announces that it will not fund any new projects for research involving chimpanzees. http://grants.nih.gov/grants/guide/notice-files/NOT-OD-12-025.html (2011).
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献