Imperial College London
Alternate

Dr Becca Asquith

Faculty of Medicine, Department of Infectious Disease

Professor of Mathematical Immunology
 
 
 
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Contact

 

+44 (0)20 7594 3731b.asquith

 
 
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Location

 

112Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Elemans:2017:10.1371/journal.ppat.1006361,
author = {Elemans, M and Boelen, L and Rasmussen, M and Buus, S and Asquith, B},
doi = {10.1371/journal.ppat.1006361},
journal = {PLOS PATHOGENS},
title = {HIV-1 adaptation to NK cell-mediated immune pressure},
url = {http://dx.doi.org/10.1371/journal.ppat.1006361},
volume = {13},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Elemans,M
AU  - Boelen,L
AU  - Rasmussen,M
AU  - Buus,S
AU  - Asquith,B
DO  - 10.1371/journal.ppat.1006361
PY  - 2017///
SN  - 1553-7366
TI  - HIV-1 adaptation to NK cell-mediated immune pressure
T2  - PLOS PATHOGENS
UR  - http://dx.doi.org/10.1371/journal.ppat.1006361
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000404511700009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/49453
VL  - 13
ER  -
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