Nature communications, 2023-12, Vol.14 (1), p.8397-8397, Article 8397
2023
Details
- Autor(en) / Beteiligte
- Titel
- Potent latency reversal by Tat RNA-containing nanoparticle enables multi-omic analysis of the HIV-1 reservoir
- Ist Teil von
- Nature communications, 2023-12, Vol.14 (1), p.8397-8397, Article 8397
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2023
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 (≈ 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-023-44020-5Titel-ID: cdi_doaj_primary_oai_doaj_org_article_3f371f7550f64091855de84f1077f564
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, AKT protein, Antiretroviral agents, Antiretroviral therapy, Antiretroviral Therapy, Highly Active, CD4 antigen, CD4 Antigens - genetics, CD4 Antigens - metabolism, CD4-Positive T-Lymphocytes - drug effects, CD4-Positive T-Lymphocytes - virology, Cell activation, Cells, Cultured, Gene Products, tat - genetics, Gene Products, tat - metabolism, HIV, HIV Core Protein p24 - genetics, HIV Core Protein p24 - metabolism, HIV Infections - drug therapy, HIV Infections - genetics, HIV Infections - virology, HIV-1 - drug effects, HIV-1 - genetics, Human immunodeficiency virus, Humans, Ionomycin, Ionomycin - pharmacology, Latency, Latent infection, Lipids, Lymphocytes, Lymphocytes T, Nanoparticles, Nanoparticles - administration & dosage, Nanoparticles - chemistry, Panobinostat - pharmacology, Proteins, Proteomes, Proviruses - drug effects, Proviruses - genetics, Ribonucleic acid, RNA, RNA, Long Noncoding - metabolism, RNA, Viral - administration & dosage, RNA, Viral - genetics, RNA, Viral - metabolism, Single-Cell Gene Expression Analysis, Tat protein, Transcriptomes, Transcriptomics, Virus Latency - drug effects, Virus Latency - genetics