1. A widely distributed HIV-1 provirus elimination assay to evaluate latency-reversing agents in vitro .
- Author
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Matsuda K, Islam S, Takada T, Tsuchiya K, Yang Tan BJ, Hattori SI, Katsuya H, Kitagawa K, Kim KS, Matsuo M, Sugata K, Delino NS, Gatanaga H, Yoshimura K, Matsushita S, Mitsuya H, Iwami S, Satou Y, and Maeda K
- Subjects
- Humans, Proviruses genetics, Virus Activation, Virus Latency, HIV-1 genetics, HIV Seropositivity, HIV Infections drug therapy
- Abstract
Persistence of HIV-1 latent reservoir cells during antiretroviral therapy (ART) is a major obstacle for curing HIV-1. Even though latency-reversing agents (LRAs) are under development to reactivate and eradicate latently infected cells, there are few useful models for evaluating LRA activity in vitro . Here, we establish a long-term cell culture system called the "widely distributed intact provirus elimination" (WIPE) assay. It harbors thousands of different HIV-1-infected cell clones with a wide distribution of HIV-1 provirus similar to that observed in vivo . Mathematical modeling and experimental results from this in vitro infection model demonstrates that the addition of an LRA to ART shows a latency-reversing effect and contributes to the eradication of replication-competent HIV-1. The WIPE assay can be used to optimize therapeutics against HIV-1 latency and investigate mechanistic insights into the clonal selection of heterogeneous HIV-1-infected cells., Competing Interests: Shingo Iwami is an employee of Science Groove Inc. The other authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (© 2021 The Author(s).)
- Published
- 2021
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