Interactions of Monocytes, HIV, and ART Identified by an Innovative scRNAseq Pipeline: Pathways to Reservoirs and HIV-Associated Comorbidities

ABSTRACT HIV reservoirs persist despite successful antiretroviral therapy (ART) and are a major obstacle to the eradication and cure of HIV. The mature monocyte subset, CD14+CD16+, contributes to viral reservoirs and HIV-associated comorbidities. Only a subset of monocytes harbors HIV (HIV+), while...

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Autores principales:	Rosiris León-Rivera, Brenda Morsey, Meng Niu, Howard S. Fox, Joan W. Berman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	HIV reservoirs latency transcriptome HIV-associated comorbidities Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c358f77e88bb4cdbafccab520569d140
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spelling	oai:doaj.org-article:c358f77e88bb4cdbafccab520569d1402021-11-15T15:56:44ZInteractions of Monocytes, HIV, and ART Identified by an Innovative scRNAseq Pipeline: Pathways to Reservoirs and HIV-Associated Comorbidities10.1128/mBio.01037-202150-7511https://doaj.org/article/c358f77e88bb4cdbafccab520569d1402020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01037-20https://doaj.org/toc/2150-7511ABSTRACT HIV reservoirs persist despite successful antiretroviral therapy (ART) and are a major obstacle to the eradication and cure of HIV. The mature monocyte subset, CD14+CD16+, contributes to viral reservoirs and HIV-associated comorbidities. Only a subset of monocytes harbors HIV (HIV+), while the rest remain uninfected, exposed cells (HIVexp). We developed an innovative single cell RNA sequencing (scRNAseq) pipeline that detects HIV and host transcripts simultaneously, enabling us to examine differences between HIV+ and HIVexp mature monocytes. Using this, we characterized uninfected, HIV+, and HIVexp primary human mature monocytes with and without ART. We showed that HIV+ mature monocytes do not form their own cluster separately from HIVexp but can be distinguished by significant differential gene expression. We found that ART decreased levels of unspliced HIV transcripts potentially by modulating host transcriptional regulators shown to decrease viral infection and replication. We also identified and characterized mature monocyte subpopulations differentially impacted by HIV and ART. We identified genes dysregulated by ART in HIVexp monocytes compared to their uninfected counterpart and, of interest, the junctional protein ALCAM, suggesting that ART impacts monocyte functions. Our data provide a novel method for simultaneous detection of HIV and host transcripts. We identify potential targets, such as those genes whose expression is increased in HIV+ mature monocytes compared to HIVexp, to block their entry into tissues, preventing establishment/replenishment of HIV reservoirs even with ART, thereby reducing and/or eliminating viral burden and HIV-associated comorbidities. Our data also highlight the heterogeneity of mature monocyte subsets and their potential contributions to HIV pathogenesis in the ART era. IMPORTANCE HIV enters tissues early after infection, leading to establishment and persistence of HIV reservoirs despite antiretroviral therapy (ART). Viral reservoirs are a major obstacle to the eradication and cure of HIV. CD14+CD16+ (mature) monocytes may contribute to establishment and reseeding of reservoirs. A subset of monocytes, consisting mainly of CD14+CD16+ cells, harbors HIV (HIV+), while the rest remain uninfected, exposed cells (HIVexp). It is important to identify cells harboring virus to eliminate reservoirs. Using an innovative single-cell RNA sequencing (scRNAseq) pipeline to detect HIV and host transcripts simultaneously, we characterized HIV+ and HIVexp primary human mature monocytes with and without ART. HIV+ mature monocytes are not a unique subpopulation but rather can be distinguished from HIVexp by differential gene expression. We characterized mature monocyte subpopulations differently impacted by HIV and ART, highlighting their potential contributions to HIV-associated comorbidities. Our data propose therapeutic targets to block HIV+ monocyte entry into tissues, preventing establishment and replenishment of reservoirs even with ART.Rosiris León-RiveraBrenda MorseyMeng NiuHoward S. FoxJoan W. BermanAmerican Society for MicrobiologyarticleHIVreservoirslatencytranscriptomeHIV-associated comorbiditiesMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV reservoirs latency transcriptome HIV-associated comorbidities Microbiology QR1-502
spellingShingle	HIV reservoirs latency transcriptome HIV-associated comorbidities Microbiology QR1-502 Rosiris León-Rivera Brenda Morsey Meng Niu Howard S. Fox Joan W. Berman Interactions of Monocytes, HIV, and ART Identified by an Innovative scRNAseq Pipeline: Pathways to Reservoirs and HIV-Associated Comorbidities
description	ABSTRACT HIV reservoirs persist despite successful antiretroviral therapy (ART) and are a major obstacle to the eradication and cure of HIV. The mature monocyte subset, CD14+CD16+, contributes to viral reservoirs and HIV-associated comorbidities. Only a subset of monocytes harbors HIV (HIV+), while the rest remain uninfected, exposed cells (HIVexp). We developed an innovative single cell RNA sequencing (scRNAseq) pipeline that detects HIV and host transcripts simultaneously, enabling us to examine differences between HIV+ and HIVexp mature monocytes. Using this, we characterized uninfected, HIV+, and HIVexp primary human mature monocytes with and without ART. We showed that HIV+ mature monocytes do not form their own cluster separately from HIVexp but can be distinguished by significant differential gene expression. We found that ART decreased levels of unspliced HIV transcripts potentially by modulating host transcriptional regulators shown to decrease viral infection and replication. We also identified and characterized mature monocyte subpopulations differentially impacted by HIV and ART. We identified genes dysregulated by ART in HIVexp monocytes compared to their uninfected counterpart and, of interest, the junctional protein ALCAM, suggesting that ART impacts monocyte functions. Our data provide a novel method for simultaneous detection of HIV and host transcripts. We identify potential targets, such as those genes whose expression is increased in HIV+ mature monocytes compared to HIVexp, to block their entry into tissues, preventing establishment/replenishment of HIV reservoirs even with ART, thereby reducing and/or eliminating viral burden and HIV-associated comorbidities. Our data also highlight the heterogeneity of mature monocyte subsets and their potential contributions to HIV pathogenesis in the ART era. IMPORTANCE HIV enters tissues early after infection, leading to establishment and persistence of HIV reservoirs despite antiretroviral therapy (ART). Viral reservoirs are a major obstacle to the eradication and cure of HIV. CD14+CD16+ (mature) monocytes may contribute to establishment and reseeding of reservoirs. A subset of monocytes, consisting mainly of CD14+CD16+ cells, harbors HIV (HIV+), while the rest remain uninfected, exposed cells (HIVexp). It is important to identify cells harboring virus to eliminate reservoirs. Using an innovative single-cell RNA sequencing (scRNAseq) pipeline to detect HIV and host transcripts simultaneously, we characterized HIV+ and HIVexp primary human mature monocytes with and without ART. HIV+ mature monocytes are not a unique subpopulation but rather can be distinguished from HIVexp by differential gene expression. We characterized mature monocyte subpopulations differently impacted by HIV and ART, highlighting their potential contributions to HIV-associated comorbidities. Our data propose therapeutic targets to block HIV+ monocyte entry into tissues, preventing establishment and replenishment of reservoirs even with ART.
format	article
author	Rosiris León-Rivera Brenda Morsey Meng Niu Howard S. Fox Joan W. Berman
author_facet	Rosiris León-Rivera Brenda Morsey Meng Niu Howard S. Fox Joan W. Berman
author_sort	Rosiris León-Rivera
title	Interactions of Monocytes, HIV, and ART Identified by an Innovative scRNAseq Pipeline: Pathways to Reservoirs and HIV-Associated Comorbidities
title_short	Interactions of Monocytes, HIV, and ART Identified by an Innovative scRNAseq Pipeline: Pathways to Reservoirs and HIV-Associated Comorbidities
title_full	Interactions of Monocytes, HIV, and ART Identified by an Innovative scRNAseq Pipeline: Pathways to Reservoirs and HIV-Associated Comorbidities
title_fullStr	Interactions of Monocytes, HIV, and ART Identified by an Innovative scRNAseq Pipeline: Pathways to Reservoirs and HIV-Associated Comorbidities
title_full_unstemmed	Interactions of Monocytes, HIV, and ART Identified by an Innovative scRNAseq Pipeline: Pathways to Reservoirs and HIV-Associated Comorbidities
title_sort	interactions of monocytes, hiv, and art identified by an innovative scrnaseq pipeline: pathways to reservoirs and hiv-associated comorbidities
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/c358f77e88bb4cdbafccab520569d140
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Interactions of Monocytes, HIV, and ART Identified by an Innovative scRNAseq Pipeline: Pathways to Reservoirs and HIV-Associated Comorbidities

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