Abstract

Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1 infection, further knowledge of their response is necessary. Here we show that NK cells responding to models of direct cell recognition, ADCC, and cytokine activation have unique transcriptional fingerprints. Compared with healthy volunteers, individuals with chronic HIV-1 infection have higher expression of genes commonly associated with activation, and lower expression of genes associated with direct cell recognition and cytokine stimulation in their NK cells. By contrast, NK cell transcriptional profiles of individuals receiving a modified vaccinia Ankara (MVA) vectored HIV-1 vaccine show upregulation of genes associated with direct cell recognition. These findings demonstrate that targeted transcriptional profiling provides a sensitive assessment of NK cell activity, which helps understand how NK cells respond to viral infections and vaccination.

Details

Title
Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination
Author
Costanzo, Margaret C 1 ; Kim, Dohoon 1 ; Creegan, Matthew 1 ; Lal, Kerri G 1 ; Ake, Julie A 2 ; Currier, Jeffrey R 3 ; Streeck, Hendrik 4 ; Robb, Merlin L 1 ; Michael, Nelson L 2 ; Bolton, Diane L 1 ; Steers, Nicholas J 5 ; Eller, Michael A 1   VIAFID ORCID Logo 

 U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA 
 U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA 
 Virus Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA 
 U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; Institute for HIV Research, University Hospital Essen, University Duisburg-Essen, Essen, Germany 
 Division of Nephrology, Columbia University Medical Center, New York, NY, USA 
Pages
1-16
Publication year
2018
Publication date
Mar 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2017394681
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.