Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors

Abstract Despite the major role of Gag in establishing resistance of HIV-1 to protease inhibitors (PIs), very limited data are available on the total contribution of Gag residues to resistance to PIs. To identify in detail Gag residues and structural interfaces associated with the development of HIV...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Francisco M Codoñer, Ruth Peña, Oscar Blanch-Lombarte, Esther Jimenez-Moyano, Maria Pino, Thomas Vollbrecht, Bonaventura Clotet, Javier Martinez-Picado, Rika Draenert, Julia G. Prado
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cda11a62772548c99100bd0b48f86fd4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cda11a62772548c99100bd0b48f86fd4
record_format	dspace
spelling	oai:doaj.org-article:cda11a62772548c99100bd0b48f86fd42021-12-02T16:08:13ZGag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors10.1038/s41598-017-03260-42045-2322https://doaj.org/article/cda11a62772548c99100bd0b48f86fd42017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03260-4https://doaj.org/toc/2045-2322Abstract Despite the major role of Gag in establishing resistance of HIV-1 to protease inhibitors (PIs), very limited data are available on the total contribution of Gag residues to resistance to PIs. To identify in detail Gag residues and structural interfaces associated with the development of HIV-1 resistance to PIs, we traced viral evolution under the pressure of PIs using Gag-protease single genome sequencing and coevolution analysis of protein sequences in 4 patients treated with PIs over a 9-year period. We identified a total of 38 Gag residues correlated with the protease, 32 of which were outside Gag cleavage sites. These residues were distributed in 23 Gag-protease groups of coevolution, with the viral matrix and the capsid represented in 87% and 52% of the groups. In addition, we uncovered the distribution of Gag correlated residues in specific protein surfaces of the inner face of the viral matrix and at the Cyclophilin A binding loop of the capsid. In summary, our findings suggest a tight interdependency between Gag structural proteins and the protease during the development of resistance of HIV-1 to PIs.Francisco M CodoñerRuth PeñaOscar Blanch-LombarteEsther Jimenez-MoyanoMaria PinoThomas VollbrechtBonaventura ClotetJavier Martinez-PicadoRika DraenertJulia G. PradoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francisco M Codoñer Ruth Peña Oscar Blanch-Lombarte Esther Jimenez-Moyano Maria Pino Thomas Vollbrecht Bonaventura Clotet Javier Martinez-Picado Rika Draenert Julia G. Prado Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors
description	Abstract Despite the major role of Gag in establishing resistance of HIV-1 to protease inhibitors (PIs), very limited data are available on the total contribution of Gag residues to resistance to PIs. To identify in detail Gag residues and structural interfaces associated with the development of HIV-1 resistance to PIs, we traced viral evolution under the pressure of PIs using Gag-protease single genome sequencing and coevolution analysis of protein sequences in 4 patients treated with PIs over a 9-year period. We identified a total of 38 Gag residues correlated with the protease, 32 of which were outside Gag cleavage sites. These residues were distributed in 23 Gag-protease groups of coevolution, with the viral matrix and the capsid represented in 87% and 52% of the groups. In addition, we uncovered the distribution of Gag correlated residues in specific protein surfaces of the inner face of the viral matrix and at the Cyclophilin A binding loop of the capsid. In summary, our findings suggest a tight interdependency between Gag structural proteins and the protease during the development of resistance of HIV-1 to PIs.
format	article
author	Francisco M Codoñer Ruth Peña Oscar Blanch-Lombarte Esther Jimenez-Moyano Maria Pino Thomas Vollbrecht Bonaventura Clotet Javier Martinez-Picado Rika Draenert Julia G. Prado
author_facet	Francisco M Codoñer Ruth Peña Oscar Blanch-Lombarte Esther Jimenez-Moyano Maria Pino Thomas Vollbrecht Bonaventura Clotet Javier Martinez-Picado Rika Draenert Julia G. Prado
author_sort	Francisco M Codoñer
title	Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors
title_short	Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors
title_full	Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors
title_fullStr	Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors
title_full_unstemmed	Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors
title_sort	gag-protease coevolution analyses define novel structural surfaces in the hiv-1 matrix and capsid involved in resistance to protease inhibitors
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cda11a62772548c99100bd0b48f86fd4
work_keys_str_mv	AT franciscomcodoner gagproteasecoevolutionanalysesdefinenovelstructuralsurfacesinthehiv1matrixandcapsidinvolvedinresistancetoproteaseinhibitors AT ruthpena gagproteasecoevolutionanalysesdefinenovelstructuralsurfacesinthehiv1matrixandcapsidinvolvedinresistancetoproteaseinhibitors AT oscarblanchlombarte gagproteasecoevolutionanalysesdefinenovelstructuralsurfacesinthehiv1matrixandcapsidinvolvedinresistancetoproteaseinhibitors AT estherjimenezmoyano gagproteasecoevolutionanalysesdefinenovelstructuralsurfacesinthehiv1matrixandcapsidinvolvedinresistancetoproteaseinhibitors AT mariapino gagproteasecoevolutionanalysesdefinenovelstructuralsurfacesinthehiv1matrixandcapsidinvolvedinresistancetoproteaseinhibitors AT thomasvollbrecht gagproteasecoevolutionanalysesdefinenovelstructuralsurfacesinthehiv1matrixandcapsidinvolvedinresistancetoproteaseinhibitors AT bonaventuraclotet gagproteasecoevolutionanalysesdefinenovelstructuralsurfacesinthehiv1matrixandcapsidinvolvedinresistancetoproteaseinhibitors AT javiermartinezpicado gagproteasecoevolutionanalysesdefinenovelstructuralsurfacesinthehiv1matrixandcapsidinvolvedinresistancetoproteaseinhibitors AT rikadraenert gagproteasecoevolutionanalysesdefinenovelstructuralsurfacesinthehiv1matrixandcapsidinvolvedinresistancetoproteaseinhibitors AT juliagprado gagproteasecoevolutionanalysesdefinenovelstructuralsurfacesinthehiv1matrixandcapsidinvolvedinresistancetoproteaseinhibitors
_version_	1718384560202317824

Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors

Ejemplares similares