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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells
Cell Host and Microbe, Volume 22, No. 1, Year 2017
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Description
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. © 2017 Elsevier Inc.
Authors & Co-Authors
Körner, Christian
Germany, Hamburg
Heinrich-pette-institut Leibniz-institut Für Experimentelle Virologie
Simoneau, Camille R.
United States, Cambridge
Massachusetts Institute of Technology
Hölzemer, Angelique
Germany, Hamburg
Heinrich-pette-institut Leibniz-institut Für Experimentelle Virologie
Germany, Hamburg
German Center for Infection Research Dzif
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Lunemann, Sebastian
Germany, Hamburg
Heinrich-pette-institut Leibniz-institut Für Experimentelle Virologie
Corleis, Björn
United States, Cambridge
Massachusetts Institute of Technology
Naranbhai, Vivek
United States, Cambridge
Massachusetts Institute of Technology
United States, Reston
Leidos Inc.
Kwon, Douglas
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Massachusetts General Hospital
Scully, Eileen P.
United States, Cambridge
Massachusetts Institute of Technology
United States, Baltimore
Johns Hopkins School of Medicine
Kirchhoff, Frank
Germany, Ulm
Universitätsklinikum Ulm
Carrington, Mary N.
United States, Cambridge
Massachusetts Institute of Technology
United States, Reston
Leidos Inc.
Altfeld, Marcus A.
Germany, Hamburg
Heinrich-pette-institut Leibniz-institut Für Experimentelle Virologie
Statistics
Citations: 31
Authors: 11
Affiliations: 10
Identifiers
Doi:
10.1016/j.chom.2017.06.008
ISSN:
19313128
Research Areas
Genetics And Genomics
Infectious Diseases