A widely-distributed HIV-1 provirus elimination assay to evaluate latency-reversing agents in vitro
Authors:
- Kouki MatsudaKMKouki Matsuda
- Saiful IslamSISaiful Islam
- Toru TakadaTTToru Takada
- Kiyoto TsuchiyaKTKiyoto Tsuchiya
- Benjy Jek Yang TanBTBenjy Jek Yang Tan
- Shin-Ichiro HattoriSHShin-Ichiro Hattori
- Hiroo KatsuyaHKHiroo Katsuya
- Kosaku KitagawaKKKosaku Kitagawa
- Kwang Su KimKKKwang Su Kim
- Misaki MatsuoMMMisaki Matsuo
- Nicole S. DelinoNDNicole S. Delino
- Hiroyuki GatanagaHGHiroyuki Gatanaga
Preprint
- 14 November 2019
- preprint
- Published by Cold Spring Harbor Laboratory in bioRxiv
- p. 842419
Abstract
Persistence of HIV-1 latent reservoir cells during antiretroviral therapy is a major obstacle for curing HIV-1. Latency-reversing agents (LRAs) are under development to reactivate and eradicate latently infected cells; however, there are few useful models for evaluating LRA activity in vitro. Here, we established a long-term cell culture system harboring thousands of different HIV-1-infected cell clones with a wide distribution of HIV-1 provirus similar to that observed in vivo. A combination of an LRA and antiretroviral therapy (ART) significantly reduced viral rebound upon treatment interruption. Experimental investigation and mathematical modeling demonstrated that addition of LRA to ART induced latency-reversing effect and contributed to the eradication of replication competent HIV-1. The widely distributed intact provirus elimination (WIPE) assay will be useful for optimizing therapeutics against HIV-1 latency and investigating mechanistic insights into the clonal selection of heterogeneous HIV-1-infected cells.Keywords
All Related Versions
- Published version: Cell Reports Methods, 1 (8), 100122.
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