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Natural Killer Cell Evasion Is Essential for Infection by Rhesus Cytomegalovirus. PLoS Pathog 2016 Aug;12(8):e1005868

Date

09/01/2016

Pubmed ID

27580123

Pubmed Central ID

PMC5006984

DOI

10.1371/journal.ppat.1005868

Scopus ID

2-s2.0-84984830187 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

The natural killer cell receptor NKG2D activates NK cells by engaging one of several ligands (NKG2DLs) belonging to either the MIC or ULBP families. Human cytomegalovirus (HCMV) UL16 and UL142 counteract this activation by retaining NKG2DLs and US18 and US20 act via lysomal degradation but the importance of NK cell evasion for infection is unknown. Since NKG2DLs are highly conserved in rhesus macaques, we characterized how NKG2DL interception by rhesus cytomegalovirus (RhCMV) impacts infection in vivo. Interestingly, RhCMV lacks homologs of UL16 and UL142 but instead employs Rh159, the homolog of UL148, to prevent NKG2DL surface expression. Rh159 resides in the endoplasmic reticulum and retains several NKG2DLs whereas UL148 does not interfere with NKG2DL expression. Deletion of Rh159 releases human and rhesus MIC proteins, but not ULBPs, from retention while increasing NK cell stimulation by infected cells. Importantly, RhCMV lacking Rh159 cannot infect CMV-naïve animals unless CD8+ cells, including NK cells, are depleted. However, infection can be rescued by replacing Rh159 with HCMV UL16 suggesting that Rh159 and UL16 perform similar functions in vivo. We therefore conclude that cytomegaloviral interference with NK cell activation is essential to establish but not to maintain chronic infection.

Author List

Sturgill ER, Malouli D, Hansen SG, Burwitz BJ, Seo S, Schneider CL, Womack JL, Verweij MC, Ventura AB, Bhusari A, Jeffries KM, Legasse AW, Axthelm MK, Hudson AW, Sacha JB, Picker LJ, Früh K

Author

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




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

Animals
Cytomegalovirus
Cytomegalovirus Infections
Humans
Immune Evasion
K562 Cells
Killer Cells, Natural
Lymphocyte Activation
Macaca fascicularis
Membrane Glycoproteins
NK Cell Lectin-Like Receptor Subfamily K
Viral Proteins