Universität zu Köln

Nolting, Anne, Dugast, Anne-Sophie, Rihn, Suzannah ORCID: 0000-0001-9495-4056, Luteijn, Rutger, Carrington, Mary F., Kane, Katherine, Jost, Stephanie, Toth, Ildiko, Nagami, Ellen, Faetkenheuer, Gerd, Hartmann, Pia, Altfeld, Marcus ORCID: 0000-0001-5972-2997 and Alter, Galit (2010). MHC class I chain-related protein A shedding in chronic HIV-1 infection is associated with profound NK cell dysfunction. Virology, 406 (1). S. 12 - 21. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 0042-6822

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Abstract

Natural killer (NK) cells play a critical role in host defense against viral infections. However chronic HIV-1 infection is associated with an accumulation of dysfunctional NK cells, that poorly control viral replication. The underlying mechanisms for this NK cell mediated dysfunction are not understood. Certain tumors evade NK cell mediated detection by dampening NK cell activity through the downregulation of NKG2D, via the release of soluble NKG2D-ligands, resulting in a potent suppression of NK cell function. Here we show that chronic HIV-1 infection is associated with a specific defect in NKG2D-mediated NK cell activation, due to reduced expression and transcription of NKG2D. Reduced NKG2D expression was associated with elevated levels of the soluble form of the NKG2D-ligand, MICA, in patient sera, likely released by HIV+CD4+ T cells. Thus, like tumors, HIV-1 may indirectly suppress NK cell recognition of HIV-1-infected CD4+ T cells by enhancing NKG2D-ligand secretion into the serum resulting in a profound impairment of NK cell function. (C) 2010 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nolting, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Dugast, Anne-Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Rihn, Suzannah UNSPECIFIED orcid.org/0000-0001-9495-4056 UNSPECIFIED Luteijn, Rutger UNSPECIFIED UNSPECIFIED UNSPECIFIED Carrington, Mary F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kane, Katherine UNSPECIFIED UNSPECIFIED UNSPECIFIED Jost, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Toth, Ildiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagami, Ellen UNSPECIFIED UNSPECIFIED UNSPECIFIED Faetkenheuer, Gerd UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Altfeld, Marcus UNSPECIFIED orcid.org/0000-0001-5972-2997 UNSPECIFIED Alter, Galit UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-494358
DOI:	10.1016/j.virol.2010.05.014
Journal or Publication Title:	Virology
Volume:	406
Number:	1
Page Range:	S. 12 - 21
Date:	2010
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	0042-6822
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NATURAL-KILLER-CELLS; T-CELLS; DOWN-REGULATION; NKG2D LIGANDS; EXPRESSION; RECEPTOR; MICA; RECOGNITION; ENGAGEMENT; IMMUNORECEPTOR Multiple languages Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49435