title: Lentiviral hepatitis B pseudotype entry requires sodium taurocholate co-transporting polypeptide and additional hepatocyte-specific factors.
abstract: Hepatitis B virus (HBV) is one of the world's major unconquered infections, resulting in progressive liver disease, and current treatments rarely cure infection. A limitation to discovering new therapies is our limited knowledge of HBV entry and dissemination pathways that hinders the development of in vitro culture systems. To address this gap in our understanding we optimized the genesis of infectious lentiviral pseudoparticles (HBVpps). The recent discovery that the bile salt transporter sodium taurocholate co-transporting polypeptide (NTCP) acts as a receptor for HBV enabled us to assess the receptor dependency of HBVpp infection. HBVpps preferentially infect hepatoma cells expressing NTCP, whereas other non-liver cells engineered to express NTCP do not support infection, suggesting that additional hepatocyte-specific factors are required for HBVpp internalization. These results highlight the value of the HBVpp system to dissect the pathways of HBV entry and dissemination.
authors.affiliation: Centre for Human Virology, Viral Hepatitis Laboratory, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: L W
authors.initials: LW
authors.lastname: Meredith
authors.affiliation: Centre for Human Virology, Viral Hepatitis Laboratory, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: K
authors.initials: K
authors.lastname: Hu
authors.affiliation: Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
authors.forename: X
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Centre for Human Virology, Viral Hepatitis Laboratory, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: C R
authors.initials: CR
authors.lastname: Howard
authors.affiliation: INSERM U1110, Institut de Recherche sur les Maladies Virales et Hépatiques and Université de Strasbourg, Strasbourg, France.
authors.forename: T F
authors.initials: TF
authors.lastname: Baumert
authors.affiliation: Centre for Human Virology, Viral Hepatitis Laboratory, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: P
authors.initials: P
authors.lastname: Balfe
authors.affiliation: Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, AMC, Amsterdam, The Netherlands.
authors.forename: K F
authors.initials: KF
authors.lastname: van de Graaf
authors.affiliation: Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.|German Center for Infection Research (DZIF), Munich, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Protzer
authors.affiliation: Institute for Advanced Study, Technische Universität München, Garching, Germany.|Centre for Human Virology, Viral Hepatitis Laboratory, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: McKeating
mesh_terms: D002460:Cell Line; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000502:physiology*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D029363:Organic Anion Transporters, Sodium-Dependent; D011991:Receptors, Virus; D027981:Symporters; C071908:sodium-bile acid cotransporter