from Gavin W. G. Wilkinson, Rebecca J. Aicheler and Eddie C. Y. Wang writing in Cytomegaloviruses: From Molecular Pathogenesis to Intervention:
The efficient downregulation of HLA-I by HCMV has the clear potential to render infected cells extremely vulnerable to NK cells. Moreover, the major IE genes activate cell responses that stimulate efficient transcription of multiple ligands for NK cell activating receptors. The capacity of HCMV to persist in vivo can clearly be ascribed to its ability to modulate NK cell responses. To date 7 functions encoded by HCMV have been formally demonstrated to suppress NK cell activation. UL18 is an MHC-I homologue that binds the inhibitory receptor LIR-1, while UL40 rescues expression of HLA-E, a ligand for the inhibitory receptor CD94-NKG2A. UL16, UL142 and miR-UL112 target multiple ligands for the ubiquitous NK activating receptor NKG2D, while UL141 targets ligands for the ubiquitous activating receptors DNAM-1 and TACTILE. The UL83-encoded major tegument protein (pp65) is unique in that it binds directly to inhibit the activating receptor NKp30. It is becoming evident that a substantial proportion of the remarkable coding capacity of this virus is directed at systematically addressing the NK cell response. Outwith the immediate goal of understanding HCMV pathogenesis, research on these immunodulatory functions are providing remarkable insights into the mechanisms that regulate human NK cell responses. Recent studies demonstrate that during its lifelong persistent/latent infection, HCMV induces dramatic changes in the NK cell repertoire leading specifically to expansions of NK cell subsets expressing CD94-NKG2C, LIR-1 and CD57. There is growing interest in these changes in the NK cell response as they potentially contribute to an emerging paradox: an 'adaptive' response by a supposedly innate arm of the immune system. This amplification of specific NK cell subsets to the virus may be instrumental in controlling infections, and may also be disrupted by immunosuppression. NK cells undoubtedly play a crucial role in controlling HCMV infections. There is a compelling need to understand the mechanisms by which HCMV evades, modulates, and ultimately is recognised by 'innate' defence systems.
Further reading: Cytomegaloviruses: From Molecular Pathogenesis to Intervention