Human cytomegalovirus encodes an MHC class I-like molecule (UL142) that functions to inhibit NK cell lysis.
Clinical and low passage strains of human CMV (HCMV) encode an additional MHC class I-related molecule UL142, in addition to the previously described UL18. The UL142 open reading frame is encoded within the ULb' region which is missing from a number of common high passage laboratory strains. Cells expressing UL142 following transfection, and fibroblasts infected with a recombinant adenovirus-expressing UL142, were used to screen both polyclonal NK cells and NK cell clones, in a completely autologous system. Analysis of 100 NK cell clones derived from five donors, revealed 23 clones that were inhibited by fibroblasts expressing UL142 alone. Small-interfering RNA-mediated knockdown of UL142 mRNA expression in HCMV-infected cells resulted in increased sensitivity to lysis. From these data we conclude that UL142 is a novel HCMV-encoded MHC class I-related molecule which inhibits NK cell killing in a clonally dependent manner.
Wills
Mark R
MR
Department of Medicine, School of Clinical Medicine, University of Cambridge, United Kingdom. mrw1004@cam.ac.uk
Ashiru
Omodele
O
Reeves
Matthew B
MB
Okecha
Georgina
G
Trowsdale
John
J
Tomasec
Peter
P
Wilkinson
Gavin W G
GW
Sinclair
John
J
Sissons
J G Patrick
JG
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D036022:Capsid Proteins / Q000235:genetics*; D003587:Cytomegalovirus / Q000276:immunology*; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D005814:Genes, Viral; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000235:genetics*
D036022:Capsid Proteins; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C512704:UL142 protein, human herpesvirus 5; D014764:Viral Proteins