Cellular proteo-transcriptomic changes in the immediate early-phase of lentiviral transduction
(2021) In Microorganisms 9(11).- Abstract
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... (More)
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.
(Less)
- author
- Linkner, Tamás Richárd ; Ambrus, Viktor ; Kunkli, Balázs ; Szojka, Zsófia Ilona LU ; Kalló, Gergő ; Csősz, Éva ; Kumar, Ajneesh ; Emri, Miklós ; Tőzsér, József and Mahdi, Mohamed
- organization
- publishing date
- 2021-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- HIV-1, HIV-2, Host response, Lentiviral vectors, Proteome, Transcriptome
- in
- Microorganisms
- volume
- 9
- issue
- 11
- article number
- 2207
- publisher
- MDPI AG
- external identifiers
-
- pmid:34835333
- scopus:85117590051
- ISSN
- 2076-2607
- DOI
- 10.3390/microorganisms9112207
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- id
- 5300d3fd-d81a-4f7b-948f-2fcea73b8c81
- date added to LUP
- 2021-11-19 13:32:50
- date last changed
- 2024-06-16 23:26:16
@article{5300d3fd-d81a-4f7b-948f-2fcea73b8c81,
abstract = {{<p>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.</p>}},
author = {{Linkner, Tamás Richárd and Ambrus, Viktor and Kunkli, Balázs and Szojka, Zsófia Ilona and Kalló, Gergő and Csősz, Éva and Kumar, Ajneesh and Emri, Miklós and Tőzsér, József and Mahdi, Mohamed}},
issn = {{2076-2607}},
keywords = {{HIV-1; HIV-2; Host response; Lentiviral vectors; Proteome; Transcriptome}},
language = {{eng}},
number = {{11}},
publisher = {{MDPI AG}},
series = {{Microorganisms}},
title = {{Cellular proteo-transcriptomic changes in the immediate early-phase of lentiviral transduction}},
url = {{http://dx.doi.org/10.3390/microorganisms9112207}},
doi = {{10.3390/microorganisms9112207}},
volume = {{9}},
year = {{2021}},
}