title: Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2.
abstract: B-cell infection by hepatitis C virus (HCV) has been a controversial topic. To examine whether HCV has a genetically determined lymphotropism through a co-receptor specific for the infection by lymphotropic HCV, we established an infectious clone and chimeric virus of hepatotropic and lymphotropic HCV strains derived from an HCV-positive B-cell lymphoma. The viral envelope and 5'-UTR sequences of the lymphotropic HCV strain were responsible for the lymphotropism. Silencing of the virus sensor, RIGI, or overexpression of microRNA-122 promoted persistent viral replication in B cells. By cDNA library screening, we identified an immune cell-specific, co-stimulatory receptor B7.2 (CD86) as a co-receptor of lymphotropic HCV. Infection of B cells by HCV inhibited the recall reaction to antigen stimulation. Together, a co-receptor B7.2 enabled lymphotropic HCV to infect memory B cells, leading to inhibition of memory B-cell function and persistent HCV infection in HCV-infected hosts.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
authors.forename: Jeffrey Y
authors.initials: JY
authors.lastname: Huang
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Tahara
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
authors.forename: Yasuteru
authors.identifier: 0000-0001-5935-4346
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schechter
authors.affiliation: Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, USA.
authors.forename: Lishan
authors.identifier: 0000-0002-0350-5560
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.|Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Michael M C
authors.initials: MM
authors.lastname: Lai
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.affiliation: International Center for Infectiology Research, Team EVIR, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007 Lyon, France.
authors.forename: François-Loïc
authors.initials: FL
authors.lastname: Cosset
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
authors.forename: Jae U
authors.initials: JU
authors.lastname: Jung
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, California 90033, USA.
authors.forename: Keigo
authors.initials: K
authors.lastname: Machida
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D051940:B7-2 Antigen / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D015723:Gene Library; D057809:HEK293 Cells; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007156:Immunologic Memory; D000072640:Interferon-Induced Helicase, IFIH1 / Q000235:genetics / Q000276:immunology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D015398:Signal Transduction; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology; D056189:Viral Tropism / Q000276:immunology*; D014779:Virus Replication
chemical_list: D051940:B7-2 Antigen; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D000072640:Interferon-Induced Helicase, IFIH1