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DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?

1
Academic Department of Pediatrics, Research Unit of Congenital and Perinatal Infection, Bambino Gesù Children’s Hospital, 00165 Rome, Italy
2
Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(15), 3715; https://doi.org/10.3390/ijms20153715
Received: 4 July 2019 / Revised: 24 July 2019 / Accepted: 27 July 2019 / Published: 30 July 2019
(This article belongs to the Special Issue Advances in NK Cell Receptors and Their Ligands)
Natural Killer (NK) cells play a critical role in host defense against viral infections. The mechanisms of recognition and killing of virus-infected cells mediated by NK cells are still only partially defined. Several viruses induce, on the surface of target cells, the expression of molecules that are specifically recognized by NK cell-activating receptors. The main NK cell-activating receptors involved in the recognition and killing of virus-infected cells are NKG2D and DNAM-1. In particular, ligands for DNAM-1 are nectin/nectin-like molecules involved also in mechanisms allowing viral infection. Viruses adopt several immune evasion strategies, including those affecting NK cell-mediated immune surveillance, causing persistent viral infection and the development of virus-associated diseases. The virus’s immune evasion efficacy depends on molecules differently expressed during the various phases of infection. In this review, we overview the molecular strategies adopted by viruses, specifically cytomegalovirus (CMV), human immunodeficiency virus (HIV-1), herpes virus (HSV), Epstein-Barr virus (EBV) and hepatitis C virus (HCV), aiming to evade NK cell-mediated surveillance, with a special focus on the modulation of DNAM-1 activating receptor and its ligands in various phases of the viral life cycle. The increasing understanding of mechanisms involved in the modulation of activating ligands, together with those mediating the viral immune evasion strategies, would provide critical tools leading to design novel NK cell-based immunotherapies aiming at viral infection control, thus improving cure strategies of virus-associated diseases. View Full-Text
Keywords: NK cells; immune surveillance; DNAM-1; activating ligands; PVR; Nectin-2; viruses; viral life cycle phases NK cells; immune surveillance; DNAM-1; activating ligands; PVR; Nectin-2; viruses; viral life cycle phases
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Cifaldi, L.; Doria, M.; Cotugno, N.; Zicari, S.; Cancrini, C.; Palma, P.; Rossi, P. DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection? Int. J. Mol. Sci. 2019, 20, 3715.

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