TY - JOUR
T1 - Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques /631/326/596/1550 /631/326/596/2555 /631/326/596/2557 article
AU - Burwitz, Benjamin J.
AU - Wettengel, Jochen M.
AU - Mück-Häusl, Martin A.
AU - Ringelhan, Marc
AU - Ko, Chunkyu
AU - Festag, Marvin M.
AU - Hammond, Katherine B.
AU - Northrup, Mina
AU - Bimber, Benjamin N.
AU - Jacob, Thomas
AU - Reed, Jason S.
AU - Norris, Reed
AU - Park, Byung
AU - Moller-Tank, Sven
AU - Esser, Knud
AU - Greene, Justin M.
AU - Wu, Helen L.
AU - Abdulhaqq, Shaheed
AU - Webb, Gabriela
AU - Sutton, William F.
AU - Klug, Alex
AU - Swanson, Tonya
AU - Legasse, Alfred W.
AU - Vu, Tania Q.
AU - Asokan, Aravind
AU - Haigwood, Nancy L.
AU - Protzer, Ulrike
AU - Sacha, Jonah B.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85038431583&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-01953-y
DO - 10.1038/s41467-017-01953-y
M3 - Article
C2 - 29247188
AN - SCOPUS:85038431583
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2146
ER -
