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The Journal of Immunology, 2005, 175: 7457-7465.
Copyright © 2005 by The American Association of Immunologists

Human Cytomegalovirus Encodes an MHC Class I-Like Molecule (UL142) That Functions to Inhibit NK Cell Lysis1

Mark R. Wills2,*, Omodele Ashiru*, Matthew B. Reeves*, Georgina Okecha*, John Trowsdale{dagger}, Peter Tomasec{ddagger}, Gavin W. G. Wilkinson{ddagger}, John Sinclair* and J. G. Patrick Sissons*

* Department of Medicine, School of Clinical Medicine, and {dagger} Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; and {ddagger} Section of Infection and Immunity, Tenovus Building, School of Medicine, Cardiff University, Wales, United Kingdom

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.




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