title: Silencing the shutoff protein of Epstein-Barr virus in productively infected B cells points to (innate) targets for immune evasion.
abstract: During productive infection with Epstein-Barr virus (EBV), a dramatic suppression of cellular protein expression is caused by the viral alkaline exonuclease BGLF5. Among the proteins downregulated by BGLF5 are multiple immune components. Here, we show that shutoff reduces expression of the innate EBV-sensing Toll-like receptor-2 and the lipid antigen-presenting CD1d molecule, thereby identifying these proteins as novel targets of BGLF5. To silence BGLF5 expression in B cells undergoing productive EBV infection, we employed an shRNA approach. Viral replication still occurred in these cells, albeit with reduced late gene expression. Surface levels of a group of proteins, including immunologically relevant molecules such as CD1d and HLA class I and class II, were only partly rescued by depletion of BGLF5, suggesting that additional viral gene products interfere with their expression. Our combined approach thus provides a means to unmask novel EBV (innate) immune evasion strategies that may operate in productively infected B cells.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van Gent
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.|Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Gram
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ingrid G J
authors.initials: IGJ
authors.lastname: Boer
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ruben J
authors.initials: RJ
authors.lastname: Geerdink
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marthe F S
authors.initials: MFS
authors.lastname: Lindenbergh
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Robert Jan
authors.initials: RJ
authors.lastname: Lebbink
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Emmanuel J
authors.initials: EJ
authors.lastname: Wiertz
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.|Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maaike E
authors.initials: ME
authors.lastname: Ressing
mesh_terms: D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D003851:Deoxyribonucleases / Q000235:genetics / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D051193:Toll-Like Receptors; D014764:Viral Proteins; D003851:Deoxyribonucleases; C083203:deoxyribonuclease, Epstein-Barr virus