Potent latency reversal by Tat RNA-containing nanoparticle enables multi-omic analysis of the HIV-1 reservoir
- Author
- Marion Pardons (UGent) , Basiel Cole, Laurens Lambrechts, Willem van Snippenberg, Sofie Rutsaert (UGent) , Ytse Noppe (UGent) , Nele De Langhe (UGent) , Annemieke Dhondt (UGent) , Jerel Vega, Filmon Eyassu, Erik Nijs, Ellen Van Gulck, Daniel Boden and Linos Vandekerckhove (UGent)
- Organization
- Project
-
- Cure: Diving deep towards HIV Cure: HIV-1 reservoir characterisation on single cell/single virus level
- Development of novel assays to characterize the size and dynamics of the HIV-1 viral reservoir.
- Development of a novel assay to characterize the HIV-1 reservoir using long-read sequencing
- HIV-1 integration as a driver of clonal expansion and HIV-1 transcription during antiretroviral therapy
- Strategies against persistent HIV-1 reservoirs
- 3L000508
- Abstract
- The development of latency reversing agents that potently reactivate HIV without inducing global T cell activation would benefit the field of HIV reservoir research and could pave the way to a functional cure. Here, we explore the reactivation capacity of a lipid nanoparticle containing Tat mRNA (Tat-LNP) in CD4 T cells from people living with HIV undergoing antiretroviral therapy (ART). When combined with panobinostat, Tat-LNP induces latency reversal in a significantly higher proportion of latently infected cells compared to PMA/ionomycin (approximate to 4-fold higher). We demonstrate that Tat-LNP does not alter the transcriptome of CD4 T cells, enabling the characterization of latently infected cells in their near-native state. Upon latency reversal, we identify transcriptomic differences between infected cells carrying an inducible provirus and non-infected cells (e.g. LINC02964, GZMA, CCL5). We confirm the transcriptomic differences at the protein level and provide evidence that the long non-coding RNA LINC02964 plays a role in active HIV infection. Furthermore, p24+ cells exhibit heightened PI3K/Akt signaling, along with downregulation of protein translation, suggesting that HIV-infected cells display distinct signatures facilitating their long-term persistence. Tat-LNP represents a valuable research tool for in vitro reservoir studies as it greatly facilitates the in-depth characterization of HIV reservoir cells' transcriptome and proteome profiles. Reactivating latent HIV reservoirs could be beneficial towards a functional cure. Here, the authors show that Tat-LNP effectively reactivates HIV while preserving the cell transcriptome. Upon reactivation, p24+ cells exhibit distinct genes and pathways potentially contributing to their persistence.
- Keywords
- VALPROIC ACID, ANTIRETROVIRAL THERAPY, VIRUS REACTIVATION, INFECTED PATIENTS, T-CELLS, P-TEFB, EXPRESSION, INHIBITOR, IDENTIFICATION, TRANSCRIPTION
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HNWAGDSQZZ7CDXRBCFZHBKWV
- MLA
- Pardons, Marion, et al. “Potent Latency Reversal by Tat RNA-Containing Nanoparticle Enables Multi-Omic Analysis of the HIV-1 Reservoir.” NATURE COMMUNICATIONS, vol. 14, no. 1, Nature Portfolio, 2023, doi:10.1038/s41467-023-44020-5.
- APA
- Pardons, M., Cole, B., Lambrechts, L., van Snippenberg, W., Rutsaert, S., Noppe, Y., … Vandekerckhove, L. (2023). Potent latency reversal by Tat RNA-containing nanoparticle enables multi-omic analysis of the HIV-1 reservoir. NATURE COMMUNICATIONS, 14(1). https://doi.org/10.1038/s41467-023-44020-5
- Chicago author-date
- Pardons, Marion, Basiel Cole, Laurens Lambrechts, Willem van Snippenberg, Sofie Rutsaert, Ytse Noppe, Nele De Langhe, et al. 2023. “Potent Latency Reversal by Tat RNA-Containing Nanoparticle Enables Multi-Omic Analysis of the HIV-1 Reservoir.” NATURE COMMUNICATIONS 14 (1). https://doi.org/10.1038/s41467-023-44020-5.
- Chicago author-date (all authors)
- Pardons, Marion, Basiel Cole, Laurens Lambrechts, Willem van Snippenberg, Sofie Rutsaert, Ytse Noppe, Nele De Langhe, Annemieke Dhondt, Jerel Vega, Filmon Eyassu, Erik Nijs, Ellen Van Gulck, Daniel Boden, and Linos Vandekerckhove. 2023. “Potent Latency Reversal by Tat RNA-Containing Nanoparticle Enables Multi-Omic Analysis of the HIV-1 Reservoir.” NATURE COMMUNICATIONS 14 (1). doi:10.1038/s41467-023-44020-5.
- Vancouver
- 1.Pardons M, Cole B, Lambrechts L, van Snippenberg W, Rutsaert S, Noppe Y, et al. Potent latency reversal by Tat RNA-containing nanoparticle enables multi-omic analysis of the HIV-1 reservoir. NATURE COMMUNICATIONS. 2023;14(1).
- IEEE
- [1]M. Pardons et al., “Potent latency reversal by Tat RNA-containing nanoparticle enables multi-omic analysis of the HIV-1 reservoir,” NATURE COMMUNICATIONS, vol. 14, no. 1, 2023.
@article{01HNWAGDSQZZ7CDXRBCFZHBKWV,
abstract = {{The development of latency reversing agents that potently reactivate HIV without inducing global T cell activation would benefit the field of HIV reservoir research and could pave the way to a functional cure. Here, we explore the reactivation capacity of a lipid nanoparticle containing Tat mRNA (Tat-LNP) in CD4 T cells from people living with HIV undergoing antiretroviral therapy (ART). When combined with panobinostat, Tat-LNP induces latency reversal in a significantly higher proportion of latently infected cells compared to PMA/ionomycin (approximate to 4-fold higher). We demonstrate that Tat-LNP does not alter the transcriptome of CD4 T cells, enabling the characterization of latently infected cells in their near-native state. Upon latency reversal, we identify transcriptomic differences between infected cells carrying an inducible provirus and non-infected cells (e.g. LINC02964, GZMA, CCL5). We confirm the transcriptomic differences at the protein level and provide evidence that the long non-coding RNA LINC02964 plays a role in active HIV infection. Furthermore, p24+ cells exhibit heightened PI3K/Akt signaling, along with downregulation of protein translation, suggesting that HIV-infected cells display distinct signatures facilitating their long-term persistence. Tat-LNP represents a valuable research tool for in vitro reservoir studies as it greatly facilitates the in-depth characterization of HIV reservoir cells' transcriptome and proteome profiles.
Reactivating latent HIV reservoirs could be beneficial towards a functional cure. Here, the authors show that Tat-LNP effectively reactivates HIV while preserving the cell transcriptome. Upon reactivation, p24+ cells exhibit distinct genes and pathways potentially contributing to their persistence.}},
articleno = {{8397}},
author = {{Pardons, Marion and Cole, Basiel and Lambrechts, Laurens and van Snippenberg, Willem and Rutsaert, Sofie and Noppe, Ytse and De Langhe, Nele and Dhondt, Annemieke and Vega, Jerel and Eyassu, Filmon and Nijs, Erik and Van Gulck, Ellen and Boden, Daniel and Vandekerckhove, Linos}},
issn = {{2041-1723}},
journal = {{NATURE COMMUNICATIONS}},
keywords = {{VALPROIC ACID,ANTIRETROVIRAL THERAPY,VIRUS REACTIVATION,INFECTED PATIENTS,T-CELLS,P-TEFB,EXPRESSION,INHIBITOR,IDENTIFICATION,TRANSCRIPTION}},
language = {{eng}},
number = {{1}},
pages = {{18}},
publisher = {{Nature Portfolio}},
title = {{Potent latency reversal by Tat RNA-containing nanoparticle enables multi-omic analysis of the HIV-1 reservoir}},
url = {{http://doi.org/10.1038/s41467-023-44020-5}},
volume = {{14}},
year = {{2023}},
}
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