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Link to original content: https://doi.org/10.1038/nrmicro1066
Viral modulation of NK cell immunity | Nature Reviews Microbiology
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  • Review Article
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Viral modulation of NK cell immunity

Nature Reviews Microbiology volume 3, pages 59–69 (2005)Cite this article

Key Points

  • In this review, the authors provide an overview of natural killer (NK) cell functions with the emphasis on their role in the standoff between viruses and hosts during infection, including NK cell receptors, the mode of NK cell activation and NK cell effector functions.

  • Murine cytomegalovirus (MCMV) encodes a ligand for an activating NK cell receptor that confers resistance to MCMV in selected mouse strains.

  • Cytomegaloviruses encode proteins that are homologous to MHC class I antigens and which might function to engage inhibitory receptors on NK cells and other circulating leukocytes.

  • Herpesvirus modulation of MHC class I expression is one mechanism by which these viruses evade recognition by cytotoxic T cells, but it might also render virus-infected cells susceptible to NK cell attack.

  • Cytomegaloviruses downregulate NKG2D ligands, which enables CMV-infected cells to avoid NK cell detection.

  • Modulation of NK cell function by other viruses such as hepatitis C, HIV, molluscum contagiosum virus, ectromelia virus and herpes simplex virus are also discussed.

Abstract

Natural killer (NK) cells have been implicated in innate immune responses against viruses such as herpesviruses, which cause persistent infections in the host. In response to the selective pressure that is exerted by NK cells, many viruses have evolved strategies either to evade detection by NK cells or to modulate the activity of NK cells. Here, we review the unique relationship that exists between NK cells and viruses, with a focus on herpesviruses.

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Figure 1: NK cell recognition of MCMV-infected cells.
Figure 2: UL40 impairs NK cell recognition of HCMV-infected cells.
Figure 3: Modulation of MHC class I antigen presentation by cytomegalovirus proteins.
Figure 4: Downregulation of NKG2D ligands by HCMV UL16.

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Acknowledgements

L.L.L. is an American Cancer Society Research Professor and is funded by the National Institutes of Health. Thanks to J. Ryan and J. Bechtel for helpful discussions.

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Authors and Affiliations

  1. Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, 513 Parnassus Avenue, HSE 1001G, Box 0414, San Francisco, 94143-0414, California, USA

    Melissa B. Lodoen & Lewis L. Lanier

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  1. Melissa B. Lodoen
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  2. Lewis L. Lanier
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Correspondence to Lewis L. Lanier.

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DATABASES

Entrez

cmv1

IFN-γ

KIR2DL3

Ly49H

MICA

MICB

rhs1

TLR9

UL18

UL40

US2

US11

UL16

ULBP1

ULBP2

Glossary

CLONAL EXPANSION

When T-cell or B-cell clones that express a unique antigen receptor encounter a cognate ligand, these lymphocytes rapidly divide to increase the number of cells that express an identical antigen receptor. This is referred to as clonal expansion.

SYNAPSE

The area of contact between the outer cell membrane of an NK cell and a target cell is known as the NK synapse. NK receptors and their cognate ligands on the target cells are concentrated in this region, which allows signalling and activation of the NK cell.

SERIAL PASSAGE

Isolated virus from one infected host is used to infect another host in a process known as serial passage of the virus. During this process, viral genes might be mutated during the replication cycle unless they have an essential function for viral replication.

CONGENIC

When a polymorphic locus that is present in one strain of mice is introduced into another strain of mice by breeding the mice and selecting for the trait of interest, the newly derived mouse strain is referred to as a congenic strain. It differs from the original parental mouse strain by having a part of its genome that is derived from another strain.

MONOMORPHIC

When genes or proteins in different individuals of a species are invariant they are referred to as monomorphic, and are distinguished from other genes or proteins (polymorphic) that show variation.

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Lodoen, M., Lanier, L. Viral modulation of NK cell immunity. Nat Rev Microbiol 3, 59–69 (2005). https://doi.org/10.1038/nrmicro1066

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