title: Cyprinid Herpesvirus 3 Il10 Inhibits Inflammatory Activities of Carp Macrophages and Promotes Proliferation of Igm+ B Cells and Memory T Cells in a Manner Similar to Carp Il10.
abstract: Cyprinid herpesvirus 3 (CyHV-3) is the causative agent of a lethal disease of carp and encodes for an Il10 homolog (ORF134). Our previous studies with a recombinant ORF134-deleted strain and the derived revertant strain suggested that cyprinid herpesvirus 3 Il10 (CyHV-3 Il10 [cyhv3Il10]) is not essential for viral replication in vitro, or virulence in vivo. In apparent contrast, cyhv3Il10 is one of the most abundant proteins of the CyHV-3 secretome and is structurally very similar to carp Il10 and also human IL10. To date, studies addressing the biological activity of cyhv3Il10 on cells of its natural host have not been performed. To address the apparent contradiction between the presence of a structurally conserved Il10 homolog in the genome of CyHV-3 and the lack of a clear phenotype in vivo using recombinant cyhv3Il10-deleted viruses, we used an in vitro approach to investigate in detail whether cyhv3Il10 exerts any biological activity on carp cells. In this study, we provide direct evidence that cyhv3Il10 is biologically active and, similarly to carp Il10, signals via a conserved Stat3 pathway modulating immune cells of its natural host, carp. In vitro, cyhv3Il10 deactivates phagocytes with a prominent effect on macrophages, while also promoting proliferation of Igm(+) B cells and memory T cells. Collectively, this study demonstrates a clear biological activity of cyhv3Il10 on cells of its natural host and indicates that cyhv3Il10 is a true viral ortholog of carp Il10. Furthermore, to our knowledge, this is the first report on biological activities of a nonmammalian viral Il10 homolog.
authors.affiliation: Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University, 6708WD Wageningen, the Netherlands; and.
authors.forename: M Carla
authors.initials: MC
authors.lastname: Piazzon
authors.affiliation: Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University, 6708WD Wageningen, the Netherlands; and.
authors.forename: Annelieke S
authors.initials: AS
authors.lastname: Wentzel
authors.affiliation: Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University, 6708WD Wageningen, the Netherlands; and.
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Tijhaar
authors.affiliation: Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals and Health, Faculty of Veterinary Medicine, University of Liege, 4000 Liege, Belgium.
authors.forename: Krzysztof Ł
authors.initials: KŁ
authors.lastname: Rakus
authors.affiliation: Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals and Health, Faculty of Veterinary Medicine, University of Liege, 4000 Liege, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Vanderplasschen
authors.affiliation: Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University, 6708WD Wageningen, the Netherlands; and.
authors.forename: Geert F
authors.initials: GF
authors.lastname: Wiegertjes
authors.affiliation: Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University, 6708WD Wageningen, the Netherlands; and maria.forlenza@wur.nl.
authors.forename: Maria
authors.initials: M
authors.lastname: Forlenza
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002347:Carps / Q000276:immunology* / Q000821:virology; D029941:Fish Proteins / Q000276:immunology*; D006564:Herpesviridae / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D029941:Fish Proteins; D050796:STAT3 Transcription Factor; D014764:Viral Proteins; D016753:Interleukin-10