title: The human herpesvirus-7 (HHV-7) U21 immunoevasin subverts NK-mediated cytoxicity through modulation of MICA and MICB.
abstract: Herpesviruses have evolved numerous immune evasion strategies to facilitate establishment of lifelong persistent infections. Many herpesviruses encode gene products devoted to preventing viral antigen presentation as a means of escaping detection by cytotoxic T lymphocytes. The human herpesvirus-7 (HHV-7) U21 gene product, for example, is an immunoevasin that binds to class I major histocompatibility complex molecules and redirects them to the lysosomal compartment. Virus infection can also induce the upregulation of surface ligands that activate NK cells. Accordingly, the herpesviruses have evolved a diverse array of mechanisms to prevent NK cell engagement of NK-activating ligands on virus-infected cells. Here we demonstrate that the HHV-7 U21 gene product interferes with NK recognition. U21 can bind to the NK activating ligand ULBP1 and reroute it to the lysosomal compartment. In addition, U21 downregulates the surface expression of the NK activating ligands MICA and MICB, resulting in a reduction in NK-mediated cytotoxicity. These results suggest that this single viral protein may interfere both with CTL-mediated recognition through the downregulation of class I MHC molecules as well as NK-mediated recognition through downregulation of NK activating ligands.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Schneider
authors.forename: Amy W
authors.initials: AW
authors.lastname: Hudson
mesh_terms: D017951:Antigen Presentation; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D058851:GPI-Linked Proteins / Q000378:metabolism; D057809:HEK293 Cells; D016199:Herpesvirus 7, Human / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008247:Lysosomes; D019349:Roseolovirus Infections / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C099187:MHC class I-related chain A; C098080:MICB antigen; C488324:U21 glycoprotein, human herpesvirus 7; C423231:ULBP1 protein, human; D014764:Viral Proteins
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