The major barrier to curing HIV-1 infection is a small pool of latently infected cells that harbor replication-competent viruses, which are widely considered the origin of viral rebound when ART is interrupted. The difficulty of distinguishing latently infected cells from the vast majority of uninfected cells has represented a significant bottleneck precluding comprehensive understandings of HIV-1 latency. Here we reported and validated a newly-designed dual fluorescent reporter virus, DFV-B, infection with which in primary CD4+ T cells can directly label latently infected cells and generate a latency model that was highly physiological relevant. Applying DFV-B infection in Jurkat T cells, we generated a stable cell line model of HIV-1 latency with diverse viral integration sites. High-throughput compound screening with this model identified ACY-1215 as a potent latency reversing agent, which could be verified in other cell models and in primary CD4+ T cells from ART-suppressed individuals ex vivo. In summary, we have generated a meaningful and feasible model to directly study latently infected cells, which could open up new avenues to explore the critical events of HIV-1 latency and become a valuable tool for the research of AIDS functional cure.
All data generated or analysed during this study are included in the manuscript.
- Kai Deng
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: Human subjects: The use of PBMCs from healthy individuals was approved by the Institutional Review Board of Guangzhou Blood Center (Guangzhou, Guangdong, China). We did not have any interaction with the healthy individuals or protected information, and therefore no informed consent was required. Chronically HIV-1-infected participants sampled by this study were recruited from The Fifth Affiliated Hospital of Sun Yat-sen University (Zhuhai, Guangdong, China). This study was approved by the Ethics Review Boards of the Fifth Affiliated Hospital of Sun Yat-sen University (2018K41-1). All the participants were given written informed consent with approval of the Ethics Committees. The enrollment of HIV-1-infected individuals was based on the criteria of prolonged suppression of plasma HIV-1 viremia on cART, which is undetectable plasma HIV-1 RNA levels (less than 50 copies/ml) for a minimum of 12 months, and having high CD4+ T cell count (at least 350 cells/mm3). All HIV-1-infected participants provided written informed consent for their participation in the study and agreed with the publication of the scientific results.
- Jori Symons
© 2021, Cai et al.
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