HIV-1 adaptation to NK cell-mediated immune pressure
File(s)
Published version
Author(s)
Elemans, M
Boelen, L
Rasmussen, M
Buus, S
Asquith, B
Type
Journal Article
Abstract
The observation, by Alter et al., of the enrichment of NK cell “escape” variants in individuals carrying certain Killer-cell Immunoglobulin-like Receptor (KIR) genes is compelling evidence that natural killer (NK) cells exert selection pressure on HIV-1. Alter et al hypothesise that variant peptide, in complex with HLA class I molecules binds KIR receptors and either increases NK cell inhibition or decreases NK cell activation compared to wild type peptide thus leading to virus escape from the NK cell response. According to this hypothesis, in order for NK cells to select for an escape variant, an individual must carry both the KIR and an HLA ligand that binds the variant peptide. In this study we estimate the proportion of the population that is capable of selecting for escape variants and use both epidemiological modelling and a model-free approach to investigate whether this proportion explains the observed variant enrichment. We found that the fraction of individuals within whom the variant would have a selective advantage was low and was unable to explain the high degree of enrichment observed. We conclude that whilst Alter et al’s data is consistent with selection pressure, the mechanism that they postulate is unlikely. The importance of this work is two-fold. Firstly, it forces a re-evaluation of some of the clearest evidence that NK cells exert a protective effect in HIV-1 infection. Secondly, it implies that there is a significant aspect of immunology that is not understood: it is possible that KIRs bind much more widely than was previously appreciated; that a gene in linkage with the KIR genes is responsible for considerable peptide-dependent selection or that variant peptides are indirectly impacting KIR ligation.
Date Issued
2017-06-05
Date Acceptance
2017-04-18
Citation
PLOS PATHOGENS, 2017, 13 (6)
ISSN
1553-7366
Publisher
PUBLIC LIBRARY OF SCIENCE
Journal / Book Title
PLOS PATHOGENS
Volume
13
Issue
6
Copyright Statement
©
2017
Elemans
et al. This is an open
access
article
distributed
under
the terms
of the
Creative
Commons
Attribution
License (https://creativecommons.org/licenses/by/4.0/),
which
permits
unrestricted use, distribution, and reproduction in any medium, provided the original
author
and source
are credited.
2017
Elemans
et al. This is an open
access
article
distributed
under
the terms
of the
Creative
Commons
Attribution
License (https://creativecommons.org/licenses/by/4.0/),
which
permits
unrestricted use, distribution, and reproduction in any medium, provided the original
author
and source
are credited.
Sponsor
Commission of the European Communities
Wellcome Trust
Bloodwise (formerly LLR)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000404511700009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
317040
103865/Z/14/Z
15012
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
MHC CLASS-I
IMMUNOGLOBULIN-LIKE RECEPTOR
NATURAL-KILLER-CELLS
CD8(+) T-CELLS
HLA-C
PEPTIDE-BINDING
DOWN-REGULATION
RECOGNITION
PROGRESSION
KIR3DL1
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Article Number
ARTN e1006361