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Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques.
Burwitz, Benjamin J; Wettengel, Jochen M; Mück-Häusl, Martin A; Ringelhan, Marc; Ko, Chunkyu; Festag, Marvin M; Hammond, Katherine B; Northrup, Mina; Bimber, Benjamin N; Jacob, Thomas; Reed, Jason S; Norris, Reed; Park, Byung; Moller-Tank, Sven; Esser, Knud; Greene, Justin M; Wu, Helen L; Abdulhaqq, Shaheed; Webb, Gabriela; Sutton, William F; Klug, Alex; Swanson, Tonya; Legasse, Alfred W; Vu, Tania Q; Asokan, Aravind; Haigwood, Nancy L; Protzer, Ulrike; Sacha, Jonah B.
Afiliación
  • Burwitz BJ; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA. burwitz@ohsu.edu.
  • Wettengel JM; Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich, Munich, 81675, Germany.
  • Mück-Häusl MA; Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich, Munich, 81675, Germany.
  • Ringelhan M; Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich, Munich, 81675, Germany.
  • Ko C; Department of Internal Medicine II, Klinikum rechts der Isar Technical University of Munich, Munich, 81675, Germany.
  • Festag MM; Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich, Munich, 81675, Germany.
  • Hammond KB; Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich, Munich, 81675, Germany.
  • Northrup M; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Bimber BN; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Jacob T; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Reed JS; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, 97239, USA.
  • Norris R; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Park B; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Moller-Tank S; Public Health and Preventative Medicine, Oregon Health and Science University, Portland, OR, 97239, USA.
  • Esser K; Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Greene JM; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
  • Wu HL; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Abdulhaqq S; Institute of Virology, Technical University of Munich/Helmholtz Zentrum Munich, Munich, 81675, Germany.
  • Webb G; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Sutton WF; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Klug A; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Swanson T; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Legasse AW; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Vu TQ; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Asokan A; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Haigwood NL; Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, 97006, USA.
  • Protzer U; Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, 97239, USA.
  • Sacha JB; Center for Spatial Systems Bioscience, Oregon Health and Science University, Portland, OR, 97201, USA.
Nat Commun ; 8(1): 2146, 2017 12 15.
Article en En | MEDLINE | ID: mdl-29247188
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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Virus de la Hepatitis B / Hepatocitos / Transportadores de Anión Orgánico Sodio-Dependiente / Simportadores Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
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PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Virus de la Hepatitis B / Hepatocitos / Transportadores de Anión Orgánico Sodio-Dependiente / Simportadores Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos