title: Suppression of CD8+ T-cell recognition in the immediate-early phase of human cytomegalovirus infection.
abstract: Human cytomegalovirus (HCMV) interferes with MHC class I-restricted antigen presentation and thereby reduces recognition by CD8(+) T-cells. This interference is mediated primarily by endoplasmic reticulum-resident glycoproteins that are encoded in the US2-11 region of the viral genome. Such a suppression of recognition would be of particular importance immediately after infection, because several immunodominant viral antigens are already present in the cell in this phase. However, which of the evasion proteins gpUS2-11 interfere(s) with antigen presentation to CD8(+) T-cells at this time of infection is not known. Here we address this question, using recombinant viruses (RV) that express only one of the immunoevasins gpUS2, gpUS3 or gpUS11. Infection with RV-US3 had only a limited impact on the presentation of peptides from the CD8(+) T-cell antigens IE1 and pp65 under immediate-early (IE) conditions imposed by cycloheximide/actinomycin D blocking. Unexpectedly, both RV-US2 and RV-US11 considerably impaired the recognition of IE1 and pp65 by CD8(+) T-cells, and both US2 and, to a lesser extent, US11 were transcribed under IE conditions. Thus, gpUS2 and gpUS11 are key effectors of MHC class I immunoevasion immediately after HCMV infection.
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hesse
authors.affiliation: Clinical Cooperation Group Immunooncology, Helmholtz Zentrum München and Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ameres
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Besold
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Krauter
authors.affiliation: Clinical Cooperation Group Immunooncology, Helmholtz Zentrum München and Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Moosmann
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Plachter
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D016601:RNA-Binding Proteins / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; C118670:US2 protein, Varicellovirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D037521:Virulence Factors