Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques
Year: 2017
Type: article
Abstract: Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present. Furthermore, viral vector-mediated expression of hNTCP on hepatocytes in vivo renders rhesus macaques permissive to HBV infection. These in vivo macaque HBV infections are characterized by longitudinal HBV DNA in serum, and detection of HBV DNA, RNA, and HBV core antigen (HBcAg) in hepatocytes. Together, these results show that expressing hNTCP on macaque hepatocytes renders them susceptible to HBV infection, thereby establishing a physiologically relevant model of HBV infection to study immune clearance and test therapeutic and curative approaches.
Source: Nature Communications
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
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W2772272641