Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase.

Human immunodeficiency virus (HIV-1) is, like most pathogens, under selective pressure to escape the immune system of its host. In particular, HIV-1 can avoid recognition by cytotoxic T lymphocytes (CTLs) by altering the binding affinity of viral peptides to human leukocyte antigen (HLA) molecules,...

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Autores principales:	Rafal Mostowy, Roger D Kouyos, Ilka Hoof, Trevor Hinkley, Mojgan Haddad, Jeannette M Whitcomb, Christos J Petropoulos, Can Keşmir, Sebastian Bonhoeffer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8f3336575b1246d68a87fa26b3fd2722
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spelling	oai:doaj.org-article:8f3336575b1246d68a87fa26b3fd27222021-11-18T05:51:18ZEstimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase.1553-734X1553-735810.1371/journal.pcbi.1002525https://doaj.org/article/8f3336575b1246d68a87fa26b3fd27222012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22654656/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Human immunodeficiency virus (HIV-1) is, like most pathogens, under selective pressure to escape the immune system of its host. In particular, HIV-1 can avoid recognition by cytotoxic T lymphocytes (CTLs) by altering the binding affinity of viral peptides to human leukocyte antigen (HLA) molecules, the role of which is to present those peptides to the immune system. It is generally assumed that HLA escape mutations carry a replicative fitness cost, but these costs have not been quantified. In this study, we assess the replicative cost of mutations which are likely to escape presentation by HLA molecules in the region of HIV-1 protease and reverse transcriptase. Specifically, we combine computational approaches for prediction of in vitro replicative fitness and peptide binding affinity to HLA molecules. We find that mutations which impair binding to HLA-A molecules tend to have lower in vitro replicative fitness than mutations which do not impair binding to HLA-A molecules, suggesting that HLA-A escape mutations carry higher fitness costs than non-escape mutations. We argue that the association between fitness and HLA-A binding impairment is probably due to an intrinsic cost of escape from HLA-A molecules, and these costs are particularly strong for HLA-A alleles associated with efficient virus control. Counter-intuitively, we do not observe a significant effect in the case of HLA-B, but, as discussed, this does not argue against the relevance of HLA-B in virus control. Overall, this article points to the intriguing possibility that HLA-A molecules preferentially target more conserved regions of HIV-1, emphasizing the importance of HLA-A genes in the evolution of HIV-1 and RNA viruses in general.Rafal MostowyRoger D KouyosIlka HoofTrevor HinkleyMojgan HaddadJeannette M WhitcombChristos J PetropoulosCan KeşmirSebastian BonhoefferPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 5, p e1002525 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Rafal Mostowy Roger D Kouyos Ilka Hoof Trevor Hinkley Mojgan Haddad Jeannette M Whitcomb Christos J Petropoulos Can Keşmir Sebastian Bonhoeffer Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase.
description	Human immunodeficiency virus (HIV-1) is, like most pathogens, under selective pressure to escape the immune system of its host. In particular, HIV-1 can avoid recognition by cytotoxic T lymphocytes (CTLs) by altering the binding affinity of viral peptides to human leukocyte antigen (HLA) molecules, the role of which is to present those peptides to the immune system. It is generally assumed that HLA escape mutations carry a replicative fitness cost, but these costs have not been quantified. In this study, we assess the replicative cost of mutations which are likely to escape presentation by HLA molecules in the region of HIV-1 protease and reverse transcriptase. Specifically, we combine computational approaches for prediction of in vitro replicative fitness and peptide binding affinity to HLA molecules. We find that mutations which impair binding to HLA-A molecules tend to have lower in vitro replicative fitness than mutations which do not impair binding to HLA-A molecules, suggesting that HLA-A escape mutations carry higher fitness costs than non-escape mutations. We argue that the association between fitness and HLA-A binding impairment is probably due to an intrinsic cost of escape from HLA-A molecules, and these costs are particularly strong for HLA-A alleles associated with efficient virus control. Counter-intuitively, we do not observe a significant effect in the case of HLA-B, but, as discussed, this does not argue against the relevance of HLA-B in virus control. Overall, this article points to the intriguing possibility that HLA-A molecules preferentially target more conserved regions of HIV-1, emphasizing the importance of HLA-A genes in the evolution of HIV-1 and RNA viruses in general.
format	article
author	Rafal Mostowy Roger D Kouyos Ilka Hoof Trevor Hinkley Mojgan Haddad Jeannette M Whitcomb Christos J Petropoulos Can Keşmir Sebastian Bonhoeffer
author_facet	Rafal Mostowy Roger D Kouyos Ilka Hoof Trevor Hinkley Mojgan Haddad Jeannette M Whitcomb Christos J Petropoulos Can Keşmir Sebastian Bonhoeffer
author_sort	Rafal Mostowy
title	Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase.
title_short	Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase.
title_full	Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase.
title_fullStr	Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase.
title_full_unstemmed	Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase.
title_sort	estimating the fitness cost of escape from hla presentation in hiv-1 protease and reverse transcriptase.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8f3336575b1246d68a87fa26b3fd2722
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Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase.

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