Medical College of Wisconsin
CTSIResearch InformaticsREDCap

The human herpesvirus-7 (HHV-7) U21 immunoevasin subverts NK-mediated cytoxicity through modulation of MICA and MICB. PLoS Pathog 2011 Nov;7(11):e1002362

Date

11/22/2011

Pubmed ID

22102813

Pubmed Central ID

PMC3213103

DOI

10.1371/journal.ppat.1002362

Scopus ID

2-s2.0-81755166703 (requires institutional sign-in at Scopus site)   44 Citations

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.

Author List

Schneider CL, Hudson AW

Author

Amy W. Hudson PhD Emeritus Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antigen Presentation
Carrier Proteins
Cell Line
Cytotoxicity, Immunologic
GPI-Linked Proteins
HEK293 Cells
Herpesvirus 7, Human
Histocompatibility Antigens Class I
Humans
Intracellular Signaling Peptides and Proteins
Killer Cells, Natural
Lysosomes
Roseolovirus Infections
Viral Proteins