Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors

Abstract The elite controller (EC)-long term non-progressor (LTNP) phenotype represent a spontaneous and advantageous model of HIV-1 control in the absence of therapy. The transcriptome of peripheral blood mononuclear cells (PBMCs) collected from EC-LTNPs was sequenced by RNA-Seq and compared with t...

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Autores principales:	Francisco Díez-Fuertes, Humberto Erick De La Torre-Tarazona, Esther Calonge, Maria Pernas, María del Mar Alonso-Socas, Laura Capa, Javier García-Pérez, Anavaj Sakuntabhai, José Alcamí
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/51f159d1d79342e58cd30f0ac1758339
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spelling	oai:doaj.org-article:51f159d1d79342e58cd30f0ac17583392021-12-02T15:09:57ZTranscriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors10.1038/s41598-019-50642-x2045-2322https://doaj.org/article/51f159d1d79342e58cd30f0ac17583392019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50642-xhttps://doaj.org/toc/2045-2322Abstract The elite controller (EC)-long term non-progressor (LTNP) phenotype represent a spontaneous and advantageous model of HIV-1 control in the absence of therapy. The transcriptome of peripheral blood mononuclear cells (PBMCs) collected from EC-LTNPs was sequenced by RNA-Seq and compared with the transcriptomes from other phenotypes of disease progression. The transcript abundance estimation combined with the use of supervised classification algorithms allowed the selection of 20 genes and pseudogenes, mainly involved in interferon-regulated antiviral mechanisms and cell machineries of transcription and translation, as the best predictive genes of disease progression. Differential expression analyses between phenotypes showed an altered calcium homeostasis in EC-LTNPs evidenced by the upregulation of several membrane receptors implicated in calcium-signaling cascades and intracellular calcium-mobilization and by the overrepresentation of NFAT1/Elk-1-binding sites in the promoters of the genes differentially expressed in these individuals. A coordinated upregulation of host genes associated with HIV-1 reverse transcription and viral transcription was also observed in EC-LTNPs –i.e. p21/CDKN1A, TNF, IER3 and GADD45B. We also found an upregulation of ANKRD54 in EC-LTNPs and viremic LTNPs in comparison with typical progressors and a clear alteration of type-I interferon signaling as a consequence of viremia in typical progressors before and after receiving antiretroviral therapy.Francisco Díez-FuertesHumberto Erick De La Torre-TarazonaEsther CalongeMaria PernasMaría del Mar Alonso-SocasLaura CapaJavier García-PérezAnavaj SakuntabhaiJosé AlcamíNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francisco Díez-Fuertes Humberto Erick De La Torre-Tarazona Esther Calonge Maria Pernas María del Mar Alonso-Socas Laura Capa Javier García-Pérez Anavaj Sakuntabhai José Alcamí Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors
description	Abstract The elite controller (EC)-long term non-progressor (LTNP) phenotype represent a spontaneous and advantageous model of HIV-1 control in the absence of therapy. The transcriptome of peripheral blood mononuclear cells (PBMCs) collected from EC-LTNPs was sequenced by RNA-Seq and compared with the transcriptomes from other phenotypes of disease progression. The transcript abundance estimation combined with the use of supervised classification algorithms allowed the selection of 20 genes and pseudogenes, mainly involved in interferon-regulated antiviral mechanisms and cell machineries of transcription and translation, as the best predictive genes of disease progression. Differential expression analyses between phenotypes showed an altered calcium homeostasis in EC-LTNPs evidenced by the upregulation of several membrane receptors implicated in calcium-signaling cascades and intracellular calcium-mobilization and by the overrepresentation of NFAT1/Elk-1-binding sites in the promoters of the genes differentially expressed in these individuals. A coordinated upregulation of host genes associated with HIV-1 reverse transcription and viral transcription was also observed in EC-LTNPs –i.e. p21/CDKN1A, TNF, IER3 and GADD45B. We also found an upregulation of ANKRD54 in EC-LTNPs and viremic LTNPs in comparison with typical progressors and a clear alteration of type-I interferon signaling as a consequence of viremia in typical progressors before and after receiving antiretroviral therapy.
format	article
author	Francisco Díez-Fuertes Humberto Erick De La Torre-Tarazona Esther Calonge Maria Pernas María del Mar Alonso-Socas Laura Capa Javier García-Pérez Anavaj Sakuntabhai José Alcamí
author_facet	Francisco Díez-Fuertes Humberto Erick De La Torre-Tarazona Esther Calonge Maria Pernas María del Mar Alonso-Socas Laura Capa Javier García-Pérez Anavaj Sakuntabhai José Alcamí
author_sort	Francisco Díez-Fuertes
title	Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors
title_short	Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors
title_full	Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors
title_fullStr	Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors
title_full_unstemmed	Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors
title_sort	transcriptome sequencing of peripheral blood mononuclear cells from elite controller-long term non progressors
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/51f159d1d79342e58cd30f0ac1758339
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Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors

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