Skip NavigationSkip to Content
Return Return to Search Results

HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells

  1. Author:
    Körner, Christian
    Simoneau, Camille R
    Schommers, Philipp
    Granoff, Mitchell
    Ziegler, Maja
    Hölzemer, Angelique
    Lunemann, Sebastian
    Chukwukelu, Janet
    Corleis, Björn
    Naranbhai, Vivek
    Kwon, Douglas S
    Scully, Eileen P
    Jost, Stephanie
    Kirchhoff, Frank
    Carrington, Mary
    Altfeld, Marcus

  2. Author Address

    Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Department of Virus Immunology, 20251 Hamburg, Germany. Electronic address: christian.koerner@hpi.uni-hamburg.de., Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Department of Virus Immunology, 20251 Hamburg, Germany; Department I of Internal Medicine, University Hospital Cologne, 50937 Cologne, Germany; German Center for Infection Research (DZIF), Cologne, Germany., Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Department of Virus Immunology, 20251 Hamburg, Germany; German Center for Infection Research (DZIF), Hamburg, Germany; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Department of Virus Immunology, 20251 Hamburg, Germany; German Center for Infection Research (DZIF), Hamburg, Germany., Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Cancer and Inflammation Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA., Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA., Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.,
    1. Year: 2017
    2. Date: Jul 12
  2. Journal: Cell Host & Microbe
    1. 22
    2. 1
    3. Pages: 111-+
  4. Type of Article: Article
  5. Article Number: 111-119.e4
  6. ISSN: 1931-3128
  1. 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. Copyright © 2017 Elsevier Inc. All rights reserved.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.chom.2017.06.008
  3. PMID: 28704647
  4. View record in Web of Science®
  5. WOS: 000405309400014

Library Notes

  1. Fiscal Year: FY2016-2017
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel