Cargando…

HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to the T Cell Receptor Stimulus

Identification of a cellular biomarker of latent HIV infection will facilitate the latent reservoir detection, quantification, and targeting for elimination. Unfortunately, the latency biomarkers reported in the literature define only a fraction of the entire reservoir. The latent HIV reservoir may...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Xinlian, Deshmukh, Savitha, Mukim, Amey, Zhang, Jasen, Beliakova-Bethell, Nadejda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145558/
https://www.ncbi.nlm.nih.gov/pubmed/37111397
http://dx.doi.org/10.3390/pathogens12040511
_version_ 1785034362465550336
author Zhang, Xinlian
Deshmukh, Savitha
Mukim, Amey
Zhang, Jasen
Beliakova-Bethell, Nadejda
author_facet Zhang, Xinlian
Deshmukh, Savitha
Mukim, Amey
Zhang, Jasen
Beliakova-Bethell, Nadejda
author_sort Zhang, Xinlian
collection PubMed
description Identification of a cellular biomarker of latent HIV infection will facilitate the latent reservoir detection, quantification, and targeting for elimination. Unfortunately, the latency biomarkers reported in the literature define only a fraction of the entire reservoir. The latent HIV reservoir may be established in dividing cells that subsequently return to quiescence and in resting cells. The strength of the T cell receptor (TCR) signaling at the time of infection affects characteristics of the established reservoir, such as the ability to reactivate with latency reversing agents. To better understand the cellular environments before latency establishment, we characterized transcriptomic remodeling induced by the initial HIV infection in cells with differential proliferative responses to the TCR stimulus. Cell proliferation was monitored using the viable dye carboxyfluorescein diacetate succinimidyl ester. Cells that divided many times, a few times, or remained non-dividing were subjected to single-cell RNA sequencing. A subset of identified transcriptional changes induced by HIV infection was independent of the number of cell divisions; however, responses unique to different cell subsets were also detected. Some of these early gene expression changes were consistent with reported markers of latently infected cells. We pose that the latency biomarkers may depend on the cellular proliferative state at the time of infection.
format Online
Article
Text
id pubmed-10145558
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-101455582023-04-29 HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to the T Cell Receptor Stimulus Zhang, Xinlian Deshmukh, Savitha Mukim, Amey Zhang, Jasen Beliakova-Bethell, Nadejda Pathogens Article Identification of a cellular biomarker of latent HIV infection will facilitate the latent reservoir detection, quantification, and targeting for elimination. Unfortunately, the latency biomarkers reported in the literature define only a fraction of the entire reservoir. The latent HIV reservoir may be established in dividing cells that subsequently return to quiescence and in resting cells. The strength of the T cell receptor (TCR) signaling at the time of infection affects characteristics of the established reservoir, such as the ability to reactivate with latency reversing agents. To better understand the cellular environments before latency establishment, we characterized transcriptomic remodeling induced by the initial HIV infection in cells with differential proliferative responses to the TCR stimulus. Cell proliferation was monitored using the viable dye carboxyfluorescein diacetate succinimidyl ester. Cells that divided many times, a few times, or remained non-dividing were subjected to single-cell RNA sequencing. A subset of identified transcriptional changes induced by HIV infection was independent of the number of cell divisions; however, responses unique to different cell subsets were also detected. Some of these early gene expression changes were consistent with reported markers of latently infected cells. We pose that the latency biomarkers may depend on the cellular proliferative state at the time of infection. MDPI 2023-03-24 /pmc/articles/PMC10145558/ /pubmed/37111397 http://dx.doi.org/10.3390/pathogens12040511 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Xinlian
Deshmukh, Savitha
Mukim, Amey
Zhang, Jasen
Beliakova-Bethell, Nadejda
HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to the T Cell Receptor Stimulus
title HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to the T Cell Receptor Stimulus
title_full HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to the T Cell Receptor Stimulus
title_fullStr HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to the T Cell Receptor Stimulus
title_full_unstemmed HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to the T Cell Receptor Stimulus
title_short HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to the T Cell Receptor Stimulus
title_sort hiv infection elicits differential transcriptomic remodeling in cd4+ t cells with variable proliferative responses to the t cell receptor stimulus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145558/
https://www.ncbi.nlm.nih.gov/pubmed/37111397
http://dx.doi.org/10.3390/pathogens12040511
work_keys_str_mv AT zhangxinlian hivinfectionelicitsdifferentialtranscriptomicremodelingincd4tcellswithvariableproliferativeresponsestothetcellreceptorstimulus
AT deshmukhsavitha hivinfectionelicitsdifferentialtranscriptomicremodelingincd4tcellswithvariableproliferativeresponsestothetcellreceptorstimulus
AT mukimamey hivinfectionelicitsdifferentialtranscriptomicremodelingincd4tcellswithvariableproliferativeresponsestothetcellreceptorstimulus
AT zhangjasen hivinfectionelicitsdifferentialtranscriptomicremodelingincd4tcellswithvariableproliferativeresponsestothetcellreceptorstimulus
AT beliakovabethellnadejda hivinfectionelicitsdifferentialtranscriptomicremodelingincd4tcellswithvariableproliferativeresponsestothetcellreceptorstimulus