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Chen, F. ; Wettengel, J.M. ; Gegenfurtner, F. ; Moosmüller, J. ; Bunse, T. ; Jeske, S. ; Hagen, P. ; Ni, Y.* ; Urban, S.* ; Protzer, U.

Identification of NTCP animal orthologs supporting hepatitis B virus binding and infection.

J. Virol. 99:e0183324 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Hepatitis B virus (HBV) infection is a significant global health threat, resulting in more than 800,000 deaths annually. Since HBV naturally infects only humans and chimpanzees, the development and evaluation of new therapies for chronic HBV infection are hindered by the lack of suitable animal models. Human sodium-taurocholate cotransporting polypeptide (NTCP) is a critical factor for HBV binding and entry, exhibiting species-specific differences in the amino acid sequences. This study investigated NTCP orthologs from various species to determine their capability to support HBV binding and infection. We demonstrate that nonhuman NTCP orthologs from woodchuck, ferret, aardvark, horse, rabbit, whale, big brown bat, cat, and rhinoceros support HBV binding and cellular entry, thereby rendering HepG2 cells susceptible to HBV infection upon expression. NTCP orthologs from hamster, goat, and cow support HBV binding but require specific amino acid exchanges to facilitate HBV infection. We show that replacement of the functional region, amino acids (aa) 84-87, in hamster NTCP with the human counterpart allows infection of HepG2 cells expressing the chimeric NTCP variant. Furthermore, we demonstrate that aa 82 in goat and cow NTCP, close to this functional region, needs to be modified to support HBV infection. This study could help identify previously unknown HBV reservoirs and may facilitate the establishment of new animal models.IMPORTANCEThe bona fide HBV entry receptor NTCP provides a natural barrier for cross-species transmission. We identified species-specific NTCP orthologues from woodchuck, ferret, aardvark, horse, rabbit, whale, big brown bat, cat, and rhinoceros that support HBV infection. This may reveal potential HBV reservoirs and facilitate the development of new HBV animal models.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Hbv Animal Models ; Hbv Infection ; Ntcp
ISSN (print) / ISBN 0022-538X
e-ISSN 1098-5514
Zeitschrift Journal of Virology
Quellenangaben Band: 99, Heft: 4, Seiten: , Artikelnummer: e0183324 Supplement: ,
Verlag American Society for Microbiology (ASM)
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)