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The Natural Killer Cell Cytotoxic Function Is Modulated by HIV-1 Accessory Proteins

Department of Immunology and Microbiology, Rush University Medical Center, 1735 West Harrison St, Chicago, IL 60612, USA
Author to whom correspondence should be addressed.
Viruses 2011, 3(7), 1091-1111;
Received: 14 June 2011 / Revised: 23 June 2011 / Accepted: 24 June 2011 / Published: 8 July 2011
(This article belongs to the Special Issue Antiviral Innate Immunity)
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Natural killer (NK) cells’ major role in the control of viruses is to eliminate established infected cells. The capacity of NK cells to kill virus-infected cells is dependent on the interactions between ligands on the infected cell and receptors on the NK cell surface. Because of the importance of ligand-receptor interactions in modulating the NK cell cytotoxic response, HIV has developed strategies to regulate various NK cell ligands making the infected cell surprisingly refractory to NK cell lysis. This is perplexing because the HIV-1 accessory protein Vpr induces expression of ligands for the NK cell activating receptor, NKG2D. In addition, the accessory protein Nef removes the inhibitory ligands HLA-A and -B. The reason for the ineffective killing by NK cells despite the strong potential to eliminate infected cells is due to HIV-1 Vpu’s ability to down modulate the co-activation ligand, NTB-A, from the cell surface. Down modulation of NTB-A prevents efficient NK cell degranulation. This review will focus on the mechanisms through which the HIV-1 accessory proteins modulate their respective ligands, and its implication for NK cell killing of HIV-infected cells.
Keywords: HIV-1; NK cells; Vpr; Vpu; Nef; NKG2D; NTB-A; PLC-γ HIV-1; NK cells; Vpr; Vpu; Nef; NKG2D; NTB-A; PLC-γ
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Sowrirajan, B.; Barker, E. The Natural Killer Cell Cytotoxic Function Is Modulated by HIV-1 Accessory Proteins. Viruses 2011, 3, 1091-1111.

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