Nature (London), 2023-02, Vol.614 (7947), p.318-325
- Clark, Iain C
- Mudvari, Prakriti
- Thaploo, Shravan
- Smith, Samuel
- Abu-Laban, Mohammad
- Hamouda, Mehdi
- Theberge, Marc
- Shah, Sakshi
- Ko, Sung Hee
- Pérez, Liliana
- Bunis, Daniel G
- Lee, James S
- Kilam, Divya
- Zakaria, Saami
- Choi, Sally
- Darko, Samuel
- Henry, Amy R
- Wheeler, Michael A
- Hoh, Rebecca
- Butrus, Salwan
- Deeks, Steven G
- Quintana, Francisco J
- Douek, Daniel C
- Abate, Adam R
- Boritz, Eli A
2023
Details
- Autor(en) / Beteiligte
- Clark, Iain C
- Mudvari, Prakriti
- Thaploo, Shravan
- Smith, Samuel
- Abu-Laban, Mohammad
- Hamouda, Mehdi
- Theberge, Marc
- Shah, Sakshi
- Ko, Sung Hee
- Pérez, Liliana
- Bunis, Daniel G
- Lee, James S
- Kilam, Divya
- Zakaria, Saami
- Choi, Sally
- Darko, Samuel
- Henry, Amy R
- Wheeler, Michael A
- Hoh, Rebecca
- Butrus, Salwan
- Deeks, Steven G
- Quintana, Francisco J
- Douek, Daniel C
- Abate, Adam R
- Boritz, Eli A
- Titel
- HIV silencing and cell survival signatures in infected T cell reservoirs
- Ist Teil von
- Nature (London), 2023-02, Vol.614 (7947), p.318-325
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2023
- Link zum Volltext
- Beschreibungen/Notizen
- Rare CD4 T cells that contain HIV under antiretroviral therapy represent an important barrier to HIV cure , but the infeasibility of isolating and characterizing these cells in their natural state has led to uncertainty about whether they possess distinctive attributes that HIV cure-directed therapies might exploit. Here we address this challenge using a microfluidic technology that isolates the transcriptomes of HIV-infected cells based solely on the detection of HIV DNA. HIV-DNA memory CD4 T cells in the blood from people receiving antiretroviral therapy showed inhibition of six transcriptomic pathways, including death receptor signalling, necroptosis signalling and antiproliferative Gα12/13 signalling. Moreover, two groups of genes identified by network co-expression analysis were significantly associated with HIV-DNA cells. These genes (n = 145) accounted for just 0.81% of the measured transcriptome and included negative regulators of HIV transcription that were higher in HIV-DNA cells, positive regulators of HIV transcription that were lower in HIV-DNA cells, and other genes involved in RNA processing, negative regulation of mRNA translation, and regulation of cell state and fate. These findings reveal that HIV-infected memory CD4 T cells under antiretroviral therapy are a distinctive population with host gene expression patterns that favour HIV silencing, cell survival and cell proliferation, with important implications for the development of HIV cure strategies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/s41586-022-05556-6Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9908556
- Format
- –
- Schlagworte
- Anti-Retroviral Agents - pharmacology, Anti-Retroviral Agents - therapeutic use, Antiretroviral agents, Antiretroviral therapy, CD4 antigen, CD4-Positive T-Lymphocytes - cytology, CD4-Positive T-Lymphocytes - drug effects, CD4-Positive T-Lymphocytes - metabolism, CD4-Positive T-Lymphocytes - virology, Cell growth, Cell proliferation, Cell Proliferation - drug effects, Cell survival, Cell Survival - drug effects, Deoxyribonucleic acid, DNA, DNA, Viral - isolation & purification, Drug therapy, Gene expression, Gene Expression Regulation, Viral - drug effects, Genes, Genetic engineering, HIV, HIV Infections - drug therapy, HIV Infections - genetics, HIV Infections - immunology, HIV Infections - virology, HIV-1 - drug effects, HIV-1 - genetics, HIV-1 - isolation & purification, HIV-1 - pathogenicity, Human immunodeficiency virus, Humans, Immunologic Memory, Immunological memory, Lymphocytes, Lymphocytes T, Memory cells, Microfluidics, Necroptosis, Necroptosis - drug effects, RNA processing, Signal transduction, Signal Transduction - drug effects, Signaling, Survival, Therapy, Transcriptome - drug effects, Transcriptomes, Transcriptomics, Virus Latency - drug effects, Viruses