PMID- 35911762
OWN - NLM
STAT- MEDLINE
DCOM- 20220802
LR  - 20220818
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire 
      and Are Associated With Vpu Sequence Variations Impacting Downmodulation of 
      HLA-C.
PG  - 922252
LID - 10.3389/fimmu.2022.922252 [doi]
LID - 922252
AB  - NK cells play a pivotal role in viral immunity, utilizing a large array of 
      activating and inhibitory receptors to identify and eliminate virus-infected 
      cells. Killer-cell immunoglobulin-like receptors (KIRs) represent a highly 
      polymorphic receptor family, regulating NK cell activity and determining the 
      ability to recognize target cells. Human leukocyte antigen (HLA) class I 
      molecules serve as the primary ligand for KIRs. Herein, HLA-C stands out as being 
      the dominant ligand for the majority of KIRs. Accumulating evidence indicated 
      that interactions between HLA-C and its inhibitory KIR2DL receptors 
      (KIR2DL1/L2/L3) can drive HIV-1-mediated immune evasion and thus may contribute 
      to the intrinsic control of HIV-1 infection. Of particular interest in this 
      context is the recent observation that HIV-1 is able to adapt to host HLA-C 
      genotypes through Vpu-mediated downmodulation of HLA-C. However, our 
      understanding of the complex interplay between KIR/HLA immunogenetics, NK 
      cell-mediated immune pressure and HIV-1 immune escape is still limited. 
      Therefore, we investigated the impact of specific KIR/HLA-C combinations on the 
      NK cell receptor repertoire and HIV-1 Vpu protein sequence variations of 122 
      viremic, untreated HIV-1(+) individuals. Compared to 60 HIV-1(-) controls, HIV-1 
      infection was associated with significant changes within the NK cell receptor 
      repertoire, including reduced percentages of NK cells expressing NKG2A, CD8, and 
      KIR2DS4. In contrast, the NKG2C(+) and KIR3DL2(+) NK cell sub-populations from 
      HIV-1(+) individuals was enlarged compared to HIV-1(-) controls. Stratification 
      along KIR/HLA-C genotypes revealed a genotype-dependent expansion of KIR2DL1(+) 
      NK cells that was ultimately associated with increased binding affinities between 
      KIR2DL1 and HLA-C allotypes. Lastly, our data hinted to a preferential selection 
      of Vpu sequence variants that were associated with HLA-C downmodulation in 
      individuals with high KIR2DL/HLA-C binding affinities. Altogether, our study 
      provides evidence that HIV-1-associated changes in the KIR repertoire of NK cells 
      are to some extent predetermined by host KIR2DL/HLA-C genotypes. Furthermore, 
      analysis of Vpu sequence polymorphisms indicates that differential KIR2DL/HLA-C 
      binding affinities may serve as an additional mechanism how host genetics impact 
      immune evasion by HIV-1.
CI  - Copyright (c) 2022 Vollmers, Lobermeyer, Niehrs, Fittje, Indenbirken, Nakel, Virdi, 
      Brias, Trenkner, Sauer, Peine, Behrens, Lehmann, Meurer, Pauli, Postel, Roider, 
      Scholten, Spinner, Stephan, Wolf, Wyen, Richert, Norman, Sauter, Schmidt, 
      Hoelzemer, Altfeld and Korner.
FAU - Vollmers, Sarah
AU  - Vollmers S
AD  - Leibniz Institute of Virology, Hamburg, Germany.
FAU - Lobermeyer, Annabelle
AU  - Lobermeyer A
AD  - Leibniz Institute of Virology, Hamburg, Germany.
FAU - Niehrs, Annika
AU  - Niehrs A
AD  - Leibniz Institute of Virology, Hamburg, Germany.
FAU - Fittje, Pia
AU  - Fittje P
AD  - Leibniz Institute of Virology, Hamburg, Germany.
FAU - Indenbirken, Daniela
AU  - Indenbirken D
AD  - Leibniz Institute of Virology, Hamburg, Germany.
FAU - Nakel, Jacqueline
AU  - Nakel J
AD  - Leibniz Institute of Virology, Hamburg, Germany.
FAU - Virdi, Sanamjeet
AU  - Virdi S
AD  - Leibniz Institute of Virology, Hamburg, Germany.
FAU - Brias, Sebastien
AU  - Brias S
AD  - Leibniz Institute of Virology, Hamburg, Germany.
AD  - First Department of Medicine, Division of Infectious Diseases, University Medical 
      Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - Trenkner, Timo
AU  - Trenkner T
AD  - Leibniz Institute of Virology, Hamburg, Germany.
FAU - Sauer, Gabriel
AU  - Sauer G
AD  - Department I for Internal Medicine, University Hospital of Cologne, Cologne, 
      Germany.
FAU - Peine, Sven
AU  - Peine S
AD  - Institute for Transfusion Medicine, University Medical Center Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Behrens, Georg M N
AU  - Behrens GMN
AD  - Department for Rheumatology and Clinical Immunology, Hannover Medical School, 
      Hannover, Germany.
FAU - Lehmann, Clara
AU  - Lehmann C
AD  - Department I for Internal Medicine, Division of Infectious Diseases, University 
      Hospital Cologne, Cologne, Germany.
AD  - German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, 
      Germany.
AD  - Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
FAU - Meurer, Anja
AU  - Meurer A
AD  - Center for Internal Medicine and Infectiology, Munich, Germany.
FAU - Pauli, Ramona
AU  - Pauli R
AD  - Medizinisches Versorgungszentrum (MVZ) am Isartor, Munich, Germany.
FAU - Postel, Nils
AU  - Postel N
AD  - Prinzmed, Practice for Infectious Diseases, Munich, Germany.
FAU - Roider, Julia
AU  - Roider J
AD  - Department of Internal Medicine IV, Department of Infectious Diseases, 
      Ludwig-Maximilians University Munich, Munich, Germany.
AD  - German Center for Infection Research (DZIF), Partner Site Munich, Munich, 
      Germany.
FAU - Scholten, Stefan
AU  - Scholten S
AD  - Praxis Hohenstaufenring, Cologne, Germany.
FAU - Spinner, Christoph D
AU  - Spinner CD
AD  - German Center for Infection Research (DZIF), Partner Site Munich, Munich, 
      Germany.
AD  - Technical University of Munich, School of Medicine, University Hospital rechts 
      der Isar, Department of Internal Medicine II, Munich, Germany.
FAU - Stephan, Christoph
AU  - Stephan C
AD  - Infectious Diseases Unit, Goethe-University Hospital Frankfurt, Frankfurt, 
      Germany.
FAU - Wolf, Eva
AU  - Wolf E
AD  - MUC Research, Munich, Germany.
FAU - Wyen, Christoph
AU  - Wyen C
AD  - Department I for Internal Medicine, Division of Infectious Diseases, University 
      Hospital Cologne, Cologne, Germany.
AD  - Praxis am Ebertplatz, Cologne, Germany.
FAU - Richert, Laura
AU  - Richert L
AD  - University of Bordeaux, Inserm U1219 Bordeaux Population Health, Inria Sistm, 
      Bordeaux, France.
FAU - Norman, Paul J
AU  - Norman PJ
AD  - Division of Biomedical Informatics and Personalized Medicine, University of 
      Colorado, Aurora, CO, United States.
AD  - Department of Immunology and Microbiology, University of Colorado, Aurora, CO, 
      United States.
FAU - Sauter, Jurgen
AU  - Sauter J
AD  - DKMS, Tubingen, Germany.
FAU - Schmidt, Alexander H
AU  - Schmidt AH
AD  - DKMS, Tubingen, Germany.
AD  - DKMS Life Science Lab, Dresden, Germany.
FAU - Hoelzemer, Angelique
AU  - Hoelzemer A
AD  - Leibniz Institute of Virology, Hamburg, Germany.
AD  - First Department of Medicine, Division of Infectious Diseases, University Medical 
      Center Hamburg-Eppendorf, Hamburg, Germany.
AD  - German Center for Infection Research (DZIF), Partner Site 
      Hamburg-Lubeck-Borstel-Riems, Hamburg, Germany.
FAU - Altfeld, Marcus
AU  - Altfeld M
AD  - Leibniz Institute of Virology, Hamburg, Germany.
AD  - German Center for Infection Research (DZIF), Partner Site 
      Hamburg-Lubeck-Borstel-Riems, Hamburg, Germany.
FAU - Korner, Christian
AU  - Korner C
AD  - Leibniz Institute of Virology, Hamburg, Germany.
LA  - eng
GR  - R01 AI158410/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 - 20220715
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (HLA-C Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Human Immunodeficiency Virus Proteins)
RN  - 0 (Ligands)
RN  - 0 (Receptors, KIR)
RN  - 0 (Receptors, Natural Killer Cell)
RN  - 0 (Viral Regulatory and Accessory Proteins)
RN  - 0 (Viroporin Proteins)
RN  - 0 (vpu protein, Human immunodeficiency virus 1)
SB  - IM
MH  - Genotype
MH  - *HIV Infections
MH  - *HIV-1
MH  - HLA-C Antigens/metabolism
MH  - Histocompatibility Antigens Class I/genetics
MH  - Human Immunodeficiency Virus Proteins/genetics
MH  - Humans
MH  - Killer Cells, Natural
MH  - Ligands
MH  - Receptors, KIR/metabolism
MH  - Receptors, Natural Killer Cell/metabolism
MH  - Viral Regulatory and Accessory Proteins/metabolism
MH  - Viroporin Proteins
PMC - PMC9334850
OTO - NOTNLM
OT  - HIV-1
OT  - HLA-C
OT  - KIR
OT  - NK cell
OT  - Vpu
COIS- CDS reports grants and personal fees from AbbVie, grants, fees and non-financial 
      support from Gilead Sciences, grants and personal fees from Janssen-Cilag, grants 
      and personal fees from MSD, grants from Cepheid, personal fees from GSK, grants 
      and personal fees from ViiV Healthcare, during the conduct of the study; fees 
      from AstraZeneca, other from Apeiron, grants, personal fees and non-financial 
      support from BBraun Melsungen, grants, personal fees from BioNtech, personal fees 
      from Eli Lilly, personal fees from Formycon, personal fees from Molecular 
      partners, grants and personal fees from Eli Lilly, personal fees from Roche, 
      personal fees from SOBI. The remaining authors declare that the research was 
      conducted in the absence of any commercial or financial relationships that could 
      be construed as a potential conflict of interest.
EDAT- 2022/08/02 06:00
MHDA- 2022/08/03 06:00
PMCR- 2022/01/01
CRDT- 2022/08/01 03:51
PHST- 2022/04/17 00:00 [received]
PHST- 2022/06/13 00:00 [accepted]
PHST- 2022/08/01 03:51 [entrez]
PHST- 2022/08/02 06:00 [pubmed]
PHST- 2022/08/03 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.922252 [doi]
PST - epublish
SO  - Front Immunol. 2022 Jul 15;13:922252. doi: 10.3389/fimmu.2022.922252. eCollection 
      2022.