PMID- 31253727
OWN - NLM
STAT- MEDLINE
DCOM- 20200413
LR  - 20200801
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 203
IP  - 3
DP  - 2019 Aug 1
TI  - NK Response Correlates with HIV Decrease in Pegylated IFN-alpha2a-Treated 
      Antiretroviral Therapy-Suppressed Subjects.
PG  - 705-717
LID - 10.4049/jimmunol.1801511 [doi]
AB  - We previously reported that pegylated IFN-alpha2a (Peg-IFN-alpha2a) added to 
      antiretroviral therapy (ART)-suppressed, HIV-infected subjects resulted in plasma 
      HIV control and integrated HIV DNA decrease. We now evaluated whether innate NK 
      cell activity or PBMC transcriptional profiles were associated with decreases in 
      HIV measures. Human peripheral blood was analyzed prior to Peg-IFN-alpha2a 
      administration (ART, baseline), after 5 wk of ART+Peg-IFN-alpha2a, and after 12 wk of 
      Peg-IFN-alpha2a monotherapy (primary endpoint). After 5 wk of ART+Peg-IFN-alpha2a, immune 
      subset frequencies were preserved, and induction of IFN-stimulated genes was 
      noted in all subjects except for a subset in which the lack of IFN-stimulated 
      gene induction was associated with increased expression of microRNAs. Viral 
      control during Peg-IFN-alpha2a monotherapy was associated with 1) higher levels of NK 
      cell activity and IFN-gamma-induced protein 10 (IP-10) on ART (preimmunotherapy) and 
      2) downmodulation of NK cell KIR2DL1 and KIR2DL2/DL3 expression, transcriptional 
      enrichment of expression of genes associated with NK cells in HIV controller 
      subjects, and higher ex vivo IFN-alpha-induced NK cytotoxicity after 5 wk of 
      ART+Peg-IFN-alpha2a. Integrated HIV DNA decline after immunotherapy was also 
      associated with gene expression patterns indicative of cell-mediated activation 
      and NK cytotoxicity. Overall, an increase in innate activity and NK cell 
      cytotoxicity were identified as correlates of Peg-IFN-alpha2a-mediated HIV control.
CI  - Copyright (c) 2019 by The American Association of Immunologists, Inc.
FAU - Papasavvas, Emmanouil
AU  - Papasavvas E
AD  - The Wistar Institute, Philadelphia, PA 19104.
FAU - Azzoni, Livio
AU  - Azzoni L
AD  - The Wistar Institute, Philadelphia, PA 19104.
FAU - Kossenkov, Andrew V
AU  - Kossenkov AV
AUID- ORCID: 0000-0002-1536-0418
AD  - The Wistar Institute, Philadelphia, PA 19104.
FAU - Dawany, Noor
AU  - Dawany N
AUID- ORCID: 0000-0003-2983-3893
AD  - The Children's Hospital of Philadelphia, Philadelphia, PA 19104.
FAU - Morales, Knashawn H
AU  - Morales KH
AD  - Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
FAU - Fair, Matthew
AU  - Fair M
AD  - The Wistar Institute, Philadelphia, PA 19104.
FAU - Ross, Brian N
AU  - Ross BN
AD  - The Wistar Institute, Philadelphia, PA 19104.
FAU - Lynn, Kenneth
AU  - Lynn K
AD  - Presbyterian Hospital-University of Pennsylvania Hospital, Philadelphia, PA 
      19104.
FAU - Mackiewicz, Agnieszka
AU  - Mackiewicz A
AD  - The Wistar Institute, Philadelphia, PA 19104.
FAU - Mounzer, Karam
AU  - Mounzer K
AD  - Jonathan Lax Immune Disorders Treatment Center, Philadelphia Field Initiating 
      Group for HIV-1 Trials, Philadelphia, PA 19107.
FAU - Tebas, Pablo
AU  - Tebas P
AUID- ORCID: 0000-0001-5345-7942
AD  - Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
FAU - Jacobson, Jeffrey M
AU  - Jacobson JM
AD  - Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140; and.
FAU - Kostman, Jay R
AU  - Kostman JR
AD  - John Bell Health Center, Philadelphia Field Initiating Group for HIV-1 Trials, 
      Philadelphia, PA 19107.
FAU - Showe, Louise
AU  - Showe L
AUID- ORCID: 0000-0002-7818-4220
AD  - The Wistar Institute, Philadelphia, PA 19104; lshowe@wistar.org 
      montaner@wistar.org.
FAU - Montaner, Luis J
AU  - Montaner LJ
AD  - The Wistar Institute, Philadelphia, PA 19104; lshowe@wistar.org 
      montaner@wistar.org.
LA  - eng
SI  - ClinicalTrials.gov/NCT02227277
GR  - P30 AI045008/AI/NIAID NIH HHS/United States
GR  - P30 CA010815/CA/NCI NIH HHS/United States
GR  - U01 AI065279/AI/NIAID NIH HHS/United States
GR  - UM1 AI126620/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190628
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CXCL10 protein, human)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Interferon-alpha)
RN  - 0 (KIR2DL1 protein, human)
RN  - 0 (KIR2DL2 protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Receptors, KIR2DL1)
RN  - 0 (Receptors, KIR2DL2)
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - Q46947FE7K (peginterferon alfa-2a)
SB  - IM
MH  - Antiretroviral Therapy, Highly Active/*methods
MH  - Cells, Cultured
MH  - Chemokine CXCL10/metabolism
MH  - HIV Infections/*drug therapy/immunology
MH  - HIV-1/*drug effects/immunology
MH  - Humans
MH  - Interferon-alpha/*therapeutic use
MH  - Killer Cells, Natural/*immunology
MH  - MicroRNAs/biosynthesis/genetics
MH  - Polyethylene Glycols/*therapeutic use
MH  - Receptors, KIR2DL1/biosynthesis
MH  - Receptors, KIR2DL2/biosynthesis
MH  - Recombinant Proteins/therapeutic use
PMC - PMC6650342
MID - NIHMS1531286
COIS- Conflicts of interest statement The authors have declared that no conflict of 
      interest exists.
EDAT- 2019/06/30 06:00
MHDA- 2020/04/14 06:00
PMCR- 2020/08/01
CRDT- 2019/06/30 06:00
PHST- 2018/11/14 00:00 [received]
PHST- 2019/06/03 00:00 [accepted]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2020/04/14 06:00 [medline]
PHST- 2019/06/30 06:00 [entrez]
PHST- 2020/08/01 00:00 [pmc-release]
AID - jimmunol.1801511 [pii]
AID - 10.4049/jimmunol.1801511 [doi]
PST - ppublish
SO  - J Immunol. 2019 Aug 1;203(3):705-717. doi: 10.4049/jimmunol.1801511. Epub 2019 
      Jun 28.