Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction

Lentivirus-based vectors derived from human immunodeficiency viruses type 1 and 2 (HIV-1 and 2) are widely used tools in research and may also be utilized in clinical settings. Like their parental virions, they are known to depend on the cellular machinery for successful gene delivery and integratio...

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Autores principales:	Tamás Richárd Linkner, Viktor Ambrus, Balázs Kunkli, Zsófia Ilona Szojka, Gergő Kalló, Éva Csősz, Ajneesh Kumar, Miklós Emri, József Tőzsér, Mohamed Mahdi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	HIV-1 HIV-2 lentiviral vectors transcriptome proteome host response Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/33fd90d04c0d4d0c845561ded4000293
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spelling	oai:doaj.org-article:33fd90d04c0d4d0c845561ded40002932021-11-25T18:24:15ZCellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction10.3390/microorganisms91122072076-2607https://doaj.org/article/33fd90d04c0d4d0c845561ded40002932021-10-01T00:00:00Zhttps://www.mdpi.com/2076-2607/9/11/2207https://doaj.org/toc/2076-2607Lentivirus-based vectors derived from human immunodeficiency viruses type 1 and 2 (HIV-1 and 2) are widely used tools in research and may also be utilized in clinical settings. Like their parental virions, they are known to depend on the cellular machinery for successful gene delivery and integration. While most of the studies on cellular proteomic and transcriptomic changes have focused on the late phase of the transduction, studies of those changes in early time-points, especially in the case of HIV-2 based vectors, are widely lacking. Using second generation HIV-1 and 2 vesicular stomatitis virus G protein (VSV-G) pseudotyped lentiviral vectors, we transduced HEK-293T human embryonic kidney cells and carried out transcriptomic profiling at 0 and 2 h time points, with accompanying proteomic analysis at 2 h following transduction. Significant variations were observed in gene expression profile between HIV-1 and HIV-2 transduced samples. Thrombospondin 1 (THBS1), collagens (COL1A2, COL3A1), and eukaryotic translation factors (EIF3CL) in addition to various genes coding for long non-coding RNA (lncRNA) were significantly upregulated 2 h after HIV-2 transduction compared to HIV-1. Label-free quantification mass spectrometry (MS) indicated that seven proteins involved in RNA binding, mRNA transport, and chaperoning were significantly downregulated. The identification of cellular protein targets of lentiviral vectors and their effect on the cellular transcriptome will undoubtedly shed more light on their complex life cycle and may be utilized against infection by their parental lentiviruses. Furthermore, characterizing the early phase of HIV-2 infection may aid in the understanding of its pathomechanism and long incubation period.Tamás Richárd LinknerViktor AmbrusBalázs KunkliZsófia Ilona SzojkaGergő KallóÉva CsőszAjneesh KumarMiklós EmriJózsef TőzsérMohamed MahdiMDPI AGarticleHIV-1HIV-2lentiviral vectorstranscriptomeproteomehost responseBiology (General)QH301-705.5ENMicroorganisms, Vol 9, Iss 2207, p 2207 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV-1 HIV-2 lentiviral vectors transcriptome proteome host response Biology (General) QH301-705.5
spellingShingle	HIV-1 HIV-2 lentiviral vectors transcriptome proteome host response Biology (General) QH301-705.5 Tamás Richárd Linkner Viktor Ambrus Balázs Kunkli Zsófia Ilona Szojka Gergő Kalló Éva Csősz Ajneesh Kumar Miklós Emri József Tőzsér Mohamed Mahdi Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction
description	Lentivirus-based vectors derived from human immunodeficiency viruses type 1 and 2 (HIV-1 and 2) are widely used tools in research and may also be utilized in clinical settings. Like their parental virions, they are known to depend on the cellular machinery for successful gene delivery and integration. While most of the studies on cellular proteomic and transcriptomic changes have focused on the late phase of the transduction, studies of those changes in early time-points, especially in the case of HIV-2 based vectors, are widely lacking. Using second generation HIV-1 and 2 vesicular stomatitis virus G protein (VSV-G) pseudotyped lentiviral vectors, we transduced HEK-293T human embryonic kidney cells and carried out transcriptomic profiling at 0 and 2 h time points, with accompanying proteomic analysis at 2 h following transduction. Significant variations were observed in gene expression profile between HIV-1 and HIV-2 transduced samples. Thrombospondin 1 (THBS1), collagens (COL1A2, COL3A1), and eukaryotic translation factors (EIF3CL) in addition to various genes coding for long non-coding RNA (lncRNA) were significantly upregulated 2 h after HIV-2 transduction compared to HIV-1. Label-free quantification mass spectrometry (MS) indicated that seven proteins involved in RNA binding, mRNA transport, and chaperoning were significantly downregulated. The identification of cellular protein targets of lentiviral vectors and their effect on the cellular transcriptome will undoubtedly shed more light on their complex life cycle and may be utilized against infection by their parental lentiviruses. Furthermore, characterizing the early phase of HIV-2 infection may aid in the understanding of its pathomechanism and long incubation period.
format	article
author	Tamás Richárd Linkner Viktor Ambrus Balázs Kunkli Zsófia Ilona Szojka Gergő Kalló Éva Csősz Ajneesh Kumar Miklós Emri József Tőzsér Mohamed Mahdi
author_facet	Tamás Richárd Linkner Viktor Ambrus Balázs Kunkli Zsófia Ilona Szojka Gergő Kalló Éva Csősz Ajneesh Kumar Miklós Emri József Tőzsér Mohamed Mahdi
author_sort	Tamás Richárd Linkner
title	Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction
title_short	Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction
title_full	Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction
title_fullStr	Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction
title_full_unstemmed	Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction
title_sort	cellular proteo-transcriptomic changes in the immediate early-phase of lentiviral transduction
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/33fd90d04c0d4d0c845561ded4000293
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Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction

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