Koerner, Christian, Simoneau, Camille R., Schommers, Philipp ORCID: 0000-0003-3375-6800, Granoff, Mitchell, Ziegler, Maja, Hoelzemer, Angelique, Lunemann, Sebastian, Chukwukelu, Janet, Corleis, Bjorn, Naranbhai, Vivek, Kwon, Douglas S., Scully, Eileen P., Jost, Stephanie, Kirchhoff, Frank ORCID: 0000-0002-7052-2360, Carrington, Mary and Altfeld, Marcus ORCID: 0000-0001-5972-2997 (2017). HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells. Cell Host Microbe, 22 (1). S. 111 - 124. CAMBRIDGE: CELL PRESS. ISSN 1934-6069

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Abstract

It was widely accepted that HIV-1 downregulates HLA-A/B to avoid CTL recognition while leaving HLA-C unaltered in order to prevent NK cell activation by engaging inhibitory NK cell receptors, but it was recently observed that most primary isolates of HIV-1 can mediate HLA-C downmodulation. Now we report that HIV-1-mediated downmodulation of HLA-C was associated with reduced binding to its respective inhibitory receptors. Despite this, HLA-C-licensed NK cells displayed reduced antiviral activity compared to their unlicensed counterparts, potentially due to residual binding to the respective inhibitory receptors. Nevertheless, NK cells were able to sense alterations of HLA-C expression demonstrated by increased antiviral activity when exposed to viral strains with differential abilities to downmodulate HLA-C. These results suggest that the capability of HLA-C-licensed NK cells to control HIV-1 replication is determined by the strength of KIR/HLA-C interactions and is thus dependent on both host genetics and the extent of virus-mediated HLA-C downregulation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koerner, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simoneau, Camille R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schommers, PhilippUNSPECIFIEDorcid.org/0000-0003-3375-6800UNSPECIFIED
Granoff, MitchellUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziegler, MajaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoelzemer, AngeliqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lunemann, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chukwukelu, JanetUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Corleis, BjornUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Naranbhai, VivekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kwon, Douglas S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scully, Eileen P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jost, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirchhoff, FrankUNSPECIFIEDorcid.org/0000-0002-7052-2360UNSPECIFIED
Carrington, MaryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altfeld, MarcusUNSPECIFIEDorcid.org/0000-0001-5972-2997UNSPECIFIED
URN: urn:nbn:de:hbz:38-225010
DOI: 10.1016/j.chom.2017.06.008
Journal or Publication Title: Cell Host Microbe
Volume: 22
Number: 1
Page Range: S. 111 - 124
Date: 2017
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1934-6069
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NATURAL-KILLER-CELLS; VIRUS; REPLICATION; EXPRESSION; KIR3DL1; INFECTION; FREQUENCY; CAPACITY; BINDING; LYSISMultiple languages
Microbiology; Parasitology; VirologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22501

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