The WIPE assay for selection and elimination of HIV-1 provirus in vitro using latency-reversing agents

Matsuda, K.; Islam, S.; Tsuchiya, K.; Tan, B. J. Y.; Hattori, S.-i.; Katsuya, H.; Miyazato, P.; Matsuo, M.; Delino, N. S.; Gatanaga, H.; Oka, S.; Yoshimura, K.; Matsushita, S.; Mitsuya, H.; Satou, Y.; Maeda, K.

doi:10.1101/842419

bioRxiv · 10.1101/842419

The WIPE assay for selection and elimination of HIV-1 provirus in vitro using latency-reversing agents

Matsuda, K.·Islam, S.·Tsuchiya, K.·Tan, B. J. Y.·Hattori, S.-i.·Katsuya, H.·Miyazato, P.·Matsuo, M.·Delino, N. S.·Gatanaga, H.·Oka, S.·Yoshimura, K.·Matsushita, S.·Mitsuya, H.·Satou, Y.·Maeda, K.

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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.

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Matsuda, K., Islam, S., Tsuchiya, K., Tan, B. J. Y., Hattori, S.-i., Katsuya, H., Miyazato, P., Matsuo, M., Delino, N. S., Gatanaga, H., Oka, S., Yoshimura, K., Matsushita, S., Mitsuya, H., Satou, Y., Maeda, K.. 2019-11-14. The WIPE assay for selection and elimination of HIV-1 provirus in vitro using latency-reversing agents. https://doi.org/10.1101/842419

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