Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques

• DOI: 10.1038/s41467-017-01953-y
• Publication Date: 2017-12-11T18:49:22Z
• Authors: Benjamin J. Burwitz; Jochen M. Wettengel; Martin A. Mück-Häusl; Marc Ringelhan; Chunkyu Ko; Marvin M. Festag; Katherine B. Hammond; Mina Northrup; Benjamin N. Bimber; Thomas Jacob; Jason S. Reed; Reed Norris; Byung Park; Sven Moller-Tank; Knud Esser; Justin M. Greene; Helen L. Wu; Shaheed Abdulhaqq; Gabriela Webb; William F. Sutton; Alex Klug; Tonya Swanson; Alfred W. Legasse; Tania Q. Vu; Aravind Asokan; Nancy L. Haigwood; Ulrike Protzer; Jonah B. Sacha
• Keywords: cccDNA; HBcAg; Rhesus macaque; Hepatitis B

Abstract Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics urgently needed. Such efforts are impeded by lack physiologically relevant, pre-clinical animal model HBV infection. Here, we report that expression entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) present. Furthermore, viral vector-mediated hNTCP vivo renders rhesus macaques permissive to These infections characterized longitudinal serum, detection DNA, RNA, core antigen (HBcAg) hepatocytes. Together, these results show expressing them susceptible infection, thereby establishing relevant study immune clearance test therapeutic approaches.