Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients

Certain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV...

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Authors: Ramirez de Arellano, Eva, Diez Fuertes, Francisco, Aguilar, Francisco, Torre Tarazona, Humberto Erick de la, Sánchez Lara, Susana, Lao, Yolanda, Vicario, Jose Luis, García, Felipe, González García, Juan, Pulido, Federico, Gutiérrez Rodero, Felix, Moreno, Santiago, Antonio Iribarren, Jose, Viciana, Pompeyo, Vilches, Carlos, Ramos, Manuel, Capa, Laura, Alcamí, José, Val, Margarita del
Format: article
Status:Published version
Publication Date:2019
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/164828
Online Access:https://hdl.handle.net/2445/164828
Access Level:Open access
Keyword:Antígens HLA
VIH (Virus)
Polimorfisme (Cristal·lografia)
HLA histocompatibility antigens
HIV (Viruses)
Polymorphism (Crystallography)
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spelling Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patientsRamirez de Arellano, EvaDiez Fuertes, FranciscoAguilar, FranciscoTorre Tarazona, Humberto Erick de laSánchez Lara, SusanaLao, YolandaVicario, Jose LuisGarcía, FelipeGonzález García, JuanPulido, FedericoGutiérrez Rodero, FelixMoreno, SantiagoAntonio Iribarren, JoseViciana, PompeyoVilches, CarlosRamos, ManuelCapa, LauraAlcamí, JoséVal, Margarita delAntígens HLAVIH (Virus)Polimorfisme (Cristal·lografia)HLA histocompatibility antigensHIV (Viruses)Polymorphism (Crystallography)Certain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV control. In this work we present a global analysis of genetic data in the large national multicenter cohort of Spanish LTNP, which is compared with seronegative individuals and HIV-positive patients. We have analyzed whether several single-nucleotide polymorphisms (SNPs) including in key genes and certain HLA-A and B alleles could be associated with a specific HIV phenotype. A total of 846 individuals, 398 HIV-1-positive patients (213 typical progressors, 55 AIDS patients, and 130 LTNPs) and 448 HIV-negative controls, were genotyped for 15 polymorphisms and HLA-A and B alleles. Significant differences in the allele frequencies among the studied populations identified 16 LTNP-associated genetic factors, 5 of which were defined for the first time as related to LTNP phenotype: the protective effect of HLA-B39, and the detrimental impact of HLA-B18, -A24, -B08 and -A29. The remaining eleven polymorphisms confirmed previous publications, including the protective alleles HLA-B57, rs2395029 (HCP5), HLA bw4 homozygosity, HLA-B52, HLA-B27, CCR2 V64I, rs9264942 (HLA-C) and HLA-A03; and the risk allele HLA bw6 homozygosity. Notably, individual Spanish HIV-negative individuals had an average of 0.12 protective HLA alleles and SNPs, compared with an average of 1.43 protective alleles per LTNP patient, strongly suggesting positive selection of LTNP. Finally, stratification of LTNP according to viral load showed a proportional relationship between the frequency of protective alleles with control of viral load. Interestingly, no differences in the frequency of protection/risk polymorphisms were found between elite controllers and LTNPs maintaining viral loads <2.000 copies/mL throughout the follow-up.Public Library of Science (PLoS)2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion17 p.application/pdfhttps://hdl.handle.net/2445/164828Articles publicats en revistes (Medicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0220459PLoS One, 2019, vol. 14, num. 8, p. e0220459https://doi.org/10.1371/journal.pone.0220459cc-by (c) Ramirez de Arellano, Eva et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1648282026-05-29T05:05:01Z
dc.title.none.fl_str_mv Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients
title Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients
spellingShingle Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients
Ramirez de Arellano, Eva
Antígens HLA
VIH (Virus)
Polimorfisme (Cristal·lografia)
HLA histocompatibility antigens
HIV (Viruses)
Polymorphism (Crystallography)
title_short Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients
title_full Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients
title_fullStr Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients
title_full_unstemmed Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients
title_sort Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients
dc.creator.none.fl_str_mv Ramirez de Arellano, Eva
Diez Fuertes, Francisco
Aguilar, Francisco
Torre Tarazona, Humberto Erick de la
Sánchez Lara, Susana
Lao, Yolanda
Vicario, Jose Luis
García, Felipe
González García, Juan
Pulido, Federico
Gutiérrez Rodero, Felix
Moreno, Santiago
Antonio Iribarren, Jose
Viciana, Pompeyo
Vilches, Carlos
Ramos, Manuel
Capa, Laura
Alcamí, José
Val, Margarita del
author Ramirez de Arellano, Eva
author_facet Ramirez de Arellano, Eva
Diez Fuertes, Francisco
Aguilar, Francisco
Torre Tarazona, Humberto Erick de la
Sánchez Lara, Susana
Lao, Yolanda
Vicario, Jose Luis
García, Felipe
González García, Juan
Pulido, Federico
Gutiérrez Rodero, Felix
Moreno, Santiago
Antonio Iribarren, Jose
Viciana, Pompeyo
Vilches, Carlos
Ramos, Manuel
Capa, Laura
Alcamí, José
Val, Margarita del
author_role author
author2 Diez Fuertes, Francisco
Aguilar, Francisco
Torre Tarazona, Humberto Erick de la
Sánchez Lara, Susana
Lao, Yolanda
Vicario, Jose Luis
García, Felipe
González García, Juan
Pulido, Federico
Gutiérrez Rodero, Felix
Moreno, Santiago
Antonio Iribarren, Jose
Viciana, Pompeyo
Vilches, Carlos
Ramos, Manuel
Capa, Laura
Alcamí, José
Val, Margarita del
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antígens HLA
VIH (Virus)
Polimorfisme (Cristal·lografia)
HLA histocompatibility antigens
HIV (Viruses)
Polymorphism (Crystallography)
topic Antígens HLA
VIH (Virus)
Polimorfisme (Cristal·lografia)
HLA histocompatibility antigens
HIV (Viruses)
Polymorphism (Crystallography)
description Certain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV control. In this work we present a global analysis of genetic data in the large national multicenter cohort of Spanish LTNP, which is compared with seronegative individuals and HIV-positive patients. We have analyzed whether several single-nucleotide polymorphisms (SNPs) including in key genes and certain HLA-A and B alleles could be associated with a specific HIV phenotype. A total of 846 individuals, 398 HIV-1-positive patients (213 typical progressors, 55 AIDS patients, and 130 LTNPs) and 448 HIV-negative controls, were genotyped for 15 polymorphisms and HLA-A and B alleles. Significant differences in the allele frequencies among the studied populations identified 16 LTNP-associated genetic factors, 5 of which were defined for the first time as related to LTNP phenotype: the protective effect of HLA-B39, and the detrimental impact of HLA-B18, -A24, -B08 and -A29. The remaining eleven polymorphisms confirmed previous publications, including the protective alleles HLA-B57, rs2395029 (HCP5), HLA bw4 homozygosity, HLA-B52, HLA-B27, CCR2 V64I, rs9264942 (HLA-C) and HLA-A03; and the risk allele HLA bw6 homozygosity. Notably, individual Spanish HIV-negative individuals had an average of 0.12 protective HLA alleles and SNPs, compared with an average of 1.43 protective alleles per LTNP patient, strongly suggesting positive selection of LTNP. Finally, stratification of LTNP according to viral load showed a proportional relationship between the frequency of protective alleles with control of viral load. Interestingly, no differences in the frequency of protection/risk polymorphisms were found between elite controllers and LTNPs maintaining viral loads <2.000 copies/mL throughout the follow-up.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/164828
url https://hdl.handle.net/2445/164828
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0220459
PLoS One, 2019, vol. 14, num. 8, p. e0220459
https://doi.org/10.1371/journal.pone.0220459
dc.rights.none.fl_str_mv cc-by (c) Ramirez de Arellano, Eva et al., 2019
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ramirez de Arellano, Eva et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 17 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869405334292922368
score 15,198674

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