@article{6e081f2a861a4c119a08326ddd1d1610,
title = "HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells",
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.",
keywords = "HIV-1, HLA class I, HLA-C, KIR, natural killer cells, NK cells",
author = "Christian K{\"o}rner and Simoneau, \{Camille R.\} and Philipp Schommers and Mitchell Granoff and Maja Ziegler and Angelique H{\"o}lzemer and Sebastian Lunemann and Janet Chukwukelu and Bj{\"o}rn Corleis and Vivek Naranbhai and Kwon, \{Douglas S.\} and Scully, \{Eileen P.\} and Stephanie Jost and Frank Kirchhoff and Mary Carrington and Marcus Altfeld",
note = "Funding Information: The following reagents were obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: pYK-JRCSF from Dr. Irvin S.Y. Chen and Dr. Yoshio Koyanagi and pNL4-3 from Dr. Malcolm Martin. The authors gratefully acknowledge the support of the Ragon Institute Flow Cytometry core and Virology platform. This study was supported by the NIH (R01-AI067031-08) and the Pathogenesis Program of the Heinrich Pette Institute, a Leibniz Institute for Experimental Virology. P.S., A.H., and J.C. were supported by the German Center for Infection Research (TI07.001, TI07.002, and TI07.003). S.L. was supported by the German Research Foundation (DFG) through the SFB841. E.P.S. was supported by a grant from the Creative and Novel Ideas in HIV Research Program (CNIHR) through a supplement to the University of California at San Francisco (UCSF) Center for AIDS Research funding (P30 AI027763). S.J. was supported by the NIH (R01-AI116363-03). F.K. is supported by an ERC Advanced grant (Anti-Virome) and the DFG. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = jul,
day = "12",
doi = "10.1016/j.chom.2017.06.008",
language = "English",
volume = "22",
pages = "111--119.e4",
journal = "Cell Host \& Microbe",
issn = "1931-3128",
publisher = "Elsevier",
number = "1",
}
