@article{edc298fda1c94b1493c815df7c03403b,
title = "Targeted viral adaptation generates a simian-tropic hepatitis B virus that infects marmoset cells",
abstract = "Hepatitis 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.",
author = "Yongzhen Liu and Cafiero, {Thomas R.} and Debby Park and Abhishek Biswas and Winer, {Benjamin Y.} and Cho, {Cheul H.} and Yaron Bram and Vasuretha Chandar and Connell, {Aoife K.O{\textquoteright}} and Gertje, {Hans P.} and Nicholas Crossland and Schwartz, {Robert E.} and Alexander Ploss",
note = "Funding Information: The authors thank Dr. Robert Lanford (Texas Biomedical Research Institute) for providing the WMHBV infectious clone and Dr. Stephan Urban (University of Heidelberg) for providing the Myrcludex B. We would like to thank Christina DeCoste and Katherine Rittenbach in the Molecular Biology Flow Cytometry core facility and Dr. Gary Laevsky and the Molecular Biology Confocal Microscopy Facility which is a Nikon Center of Excellence for their excellent technical support. We further thank all members of the Ploss lab, especially Dr. Robert LeDesma for critical discussions and comments throughout experimentation and preparation of the manuscript. Work in the lab is supported by grants from the National Institutes of Health (R01 AI138797, R01 AI107301, R01 AI146917, R01 AI153236 to A.P.), (R01AI107301, R01DK121072 to R.E.S.), a Burroughs Welcome Fund Award for Investigators in Pathogenesis (#101539 to A.P.) and funding from Princeton University. The Molecular Biology Flow Cytometry Resource Facility is partially supported by the Cancer Institute of New Jersey Cancer Center Support grant (P30CA072720). This work utilized NIH S10 Shared Instrumentation Grants S10-OD026983 and SS10-OD030269 (awarded to N.A.C.). Funding Information: The authors thank Dr. Robert Lanford (Texas Biomedical Research Institute) for providing the WMHBV infectious clone and Dr. Stephan Urban (University of Heidelberg) for providing the Myrcludex B. We would like to thank Christina DeCoste and Katherine Rittenbach in the Molecular Biology Flow Cytometry core facility and Dr. Gary Laevsky and the Molecular Biology Confocal Microscopy Facility which is a Nikon Center of Excellence for their excellent technical support. We further thank all members of the Ploss lab, especially Dr. Robert LeDesma for critical discussions and comments throughout experimentation and preparation of the manuscript. Work in the lab is supported by grants from the National Institutes of Health (R01 AI138797, R01 AI107301, R01 AI146917, R01 AI153236 to A.P.), (R01AI107301, R01DK121072 to R.E.S.), a Burroughs Welcome Fund Award for Investigators in Pathogenesis (#101539 to A.P.) and funding from Princeton University. The Molecular Biology Flow Cytometry Resource Facility is partially supported by the Cancer Institute of New Jersey Cancer Center Support grant (P30CA072720). This work utilized NIH S10 Shared Instrumentation Grants S10-OD026983 and SS10-OD030269 (awarded to N.A.C.). Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = dec,
doi = "10.1038/s41467-023-39148-3",
language = "English (US)",
volume = "14",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}