Mechanisms Regulating NK Cell Activation During Viral Infection

Catherine A Forbes,Jerome D Coudert

doi:10.2217/fvl.14.106

Abstract

ABSTRACT NK cells constitute a population of lymphocytes involved in innate immune functions. They play a critical role in antiviral immune surveillance. Viruses have evolved with their host species for millions of years, each exerting a selective pressure upon the other. As a corollary, the pathways used by the immune system that are critical to control viral infection can be revealed by defining the role of viral gene products that are nonessential for virus replication. We relate here the battery of resources available to NK cells to recognize and eliminate viruses and reciprocally the immune evasion mechanisms developed by viruses to prevent NK cell activation.

Highlights

Viruses and the hosts’ immune system have exerted reciprocal selective pressure for eons in their mutual race to outsmart each other
This review summarizes the mechanisms of Natural Killer (NK) cell regulation, the activation pathways relevant to NK cell recognition of virus infected-cells and the multiple immune evasion mechanisms developed by viruses, including the most recent insights into the strategies used by cytomegalovirus
Mice infected with mouse cytomegalovirus (MCMV) Δm154 were shown to display reduced viral titers compared to mice infected with MCMV WT and depletion of NK cells abolished the protection[134]; these findings indicated that m154 encodes an immunoevasin that improves the virus ability to evade NK cell anti-viral response

Summary

Introduction

Viruses and the hosts’ immune system have exerted reciprocal selective pressure for eons in their mutual race to outsmart each other. These findings indicate that NK cell responses to viral infection are regulated by activating receptors targeting viral products and by self-specific inhibitory receptors and support the importance of the H-2 background. HCMV UL40 gene product mimics the signal peptides of various HLA-C haplotypes and binds to non-classical MHC I HLA-E, which favors its expression on infected cells and limits NK cell activation[104, 105] by engaging preferentially inhibitory NKG2A but not activating NKG2C receptors[106].

Results

Conclusion