Title |
Distinct chromatin functional states correlate with HIV latency reactivation in infected primary CD4+ T cells
|
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Published in |
eLife, May 2018
|
DOI | 10.7554/elife.34655 |
Pubmed ID | |
Authors |
Emilie Battivelli, Matthew S Dahabieh, Mohamed Abdel-Mohsen, J Peter Svensson, Israel Tojal Da Silva, Lillian B Cohn, Andrea Gramatica, Steven Deeks, Warner C Greene, Satish K Pillai, Eric Verdin |
Abstract |
Human immunodeficiency virus (HIV) infection is currently incurable, due to the persistence of latently infected cells. The 'shock and kill' approach to a cure proposes to eliminate this reservoir via transcriptional activation of latent proviruses, enabling direct or indirect killing of infected cells. Currently available latency-reversing agents (LRAs) have however proven ineffective. To understand why, we used a novel HIV reporter strain in primary CD4+ T cells and determined which latently infected cells are reactivatable by current candidate LRAs. Remarkably, none of these agents reactivated more than 5% of cells carrying a latent provirus. Sequencing analysis of reactivatable vs.non-reactivatable populations revealed that the integration sites were distinguishable in terms of chromatin functional states. Our findings challenge the feasibility of 'shock and kill', and suggest the need to explore other strategies to control the latent HIV reservoir. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 5 | 26% |
United States | 4 | 21% |
India | 1 | 5% |
Sweden | 1 | 5% |
Japan | 1 | 5% |
Unknown | 7 | 37% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 13 | 68% |
Scientists | 5 | 26% |
Science communicators (journalists, bloggers, editors) | 1 | 5% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 169 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 32 | 19% |
Student > Master | 24 | 14% |
Student > Bachelor | 22 | 13% |
Researcher | 21 | 12% |
Student > Doctoral Student | 10 | 6% |
Other | 16 | 9% |
Unknown | 44 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 36 | 21% |
Immunology and Microbiology | 32 | 19% |
Agricultural and Biological Sciences | 21 | 12% |
Medicine and Dentistry | 18 | 11% |
Social Sciences | 2 | 1% |
Other | 7 | 4% |
Unknown | 53 | 31% |