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- Title
TARGETING THE HIV RESERVOIR.
- Authors
Jocelyn, Kim T.; Matthew, Marsden D.; Melanie, Dimapasoc; Paul, Wender A.; Jerome, Zack A.
- Abstract
Human immunodeficiency virus continues to be a global health concern that has claimed the lives of millions. Although anti-retroviral therapy slows disease progression, it is not curative due to certain reservoirs of replication-competent virus that persist during therapy. Therefore, if therapy is stopped, virus will emerge from these reservoirs and rapidly spread, causing renewed progression towards disease. One strategy for clearing the reservoir of latently infected cells is to use a kick and kill approach, in which latent cells are "kicked" or activated from latency, and then concurrently cleared or "killed". Latency reversal agents can "kick" or induce HIV expression from latent cells, but do not necessarily cause the activated latent cells to die. Our group has been developing synthetic protein kinase C modulators based on natural products as latency reversing agents. We have shown these compounds activate latent virus in patient samples and in virus infected drug-treated humanized mice. Natural killer cells hold great promise as killing agents for virally infected cells as they re-emerge from latency due to their innate anti-viral recognition and cytotoxic function. We have recently shown that introduction of our best characterized latency reversing agent into infected humanized mice, followed by administration of allogeneic Natural Killer cells is superior in eliminating latent virus compared with either treatment alone. The use of a barcoded virus swarm to help quantitate effects of this "Kick and kill" strategy on the viral reservoir will be discussed.
- Subjects
KILLER cells; PROTEIN kinase C; HIV; SYNTHETIC proteins; ANTIRETROVIRAL agents
- Publication
Genetics & Applications, 2023, p21
- ISSN
2566-2937
- Publication type
Article