title: Modulation of hepatitis C virus release by the interferon-induced protein BST-2/tetherin.
abstract: Hepatitis C virus is a leading cause of chronic hepatitis and liver cancer. Little information exists on the interplay between innate defense mechanisms and viral antagonists that promote viral egress. Herein, the effects of Tetherin/BST-2 on HCV release were investigated. In Huh-7.5 hepatocytes, low expression levels of BST-2 were detected. Treatment of Huh-7.5 cells with IFNα, elevated BST-2 expression levels. However, HCV could not alter the expression of IFNα-induced BST-2, nor of stably over-expressed BST-2. Significantly, over expressed BST-2 moderately blocked HCV production and release from Huh-7.5 cells. Functional analysis of BST-2, confirmed its ability to inhibit the release of HIV delta-Vpu from Huh-7.5-BST-2 cells. HIV-Vpu antagonized BST-2 activity and rescued HIV delta-Vpu release from Huh-7.5-BST-2 cells. However, vpu slightly rescued HCV release and production from Huh-7.5-BST-2. We conclude that BST-2 moderately restricts HCV production and release from Huh-7.5 hepatocytes, while the virus lacks mechanisms to counteract this restriction.
authors.affiliation: Department of Virology and Developmental Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva, Israel.
authors.forename: Avis
authors.initials: A
authors.lastname: Dafa-Berger
authors.forename: Alona
authors.initials: A
authors.lastname: Kuzmina
authors.forename: Michael
authors.initials: M
authors.lastname: Fassler
authors.forename: Hila
authors.initials: H
authors.lastname: Yitzhak-Asraf
authors.forename: Yonat
authors.initials: Y
authors.lastname: Shemer-Avni
authors.forename: Ran
authors.initials: R
authors.lastname: Taube
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D057074:Virus Release; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D016898:Interferon-alpha; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2