TY - JOUR
T1 - Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination
AU - Costanzo, Margaret C.
AU - Kim, Dohoon
AU - Creegan, Matthew
AU - Lal, Kerri G.
AU - Ake, Julie A.
AU - Currier, Jeffrey R.
AU - Streeck, Hendrik
AU - Robb, Merlin L.
AU - Michael, Nelson L.
AU - Bolton, Diane L.
AU - Steers, Nicholas J.
AU - Eller, Michael A.
N1 - Funding Information:
The authors would like to thank the study participants from the RV229, RV149, and RV262. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense, or the National Institutes of Health. This work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD).
Funding Information:
1U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20901, USA. 2Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr., Bethesda, MD 20817, USA. 3Virus Diseases Branch, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20901, USA. 4Institute for HIV Research, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. 5Division of Nephrology, Columbia University Medical Center, 1150 St. Nicholas Ave., New York, NY 10032, USA. Correspondence and requests for materials should be addressed to M.A.E. (email: meller@hivresearch.org)
Funding Information:
The authors would like to thank the study participants from the RV229, RV149, and RV262. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense, or the National Institutes of Health. This work was supported by a cooperative agreement (W81XWH- 07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85044353148&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-03618-w
DO - 10.1038/s41467-018-03618-w
M3 - Article
C2 - 29572470
AN - SCOPUS:85044353148
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1212
ER -