HIV is difficult to eradicate due to the persistence of a long-lived reservoir of latently infected cells. Previous studies have shown that natural killer cells are important to inhibiting HIV infection, but it is unclear whether the administration of natural killer cells can reduce rebound viremia when anti-retroviral therapy is discontinued. Here we show the administration of allogeneic human peripheral blood natural killer cells delays viral rebound following interruption of anti-retroviral therapy in humanized mice infected with HIV-1. Utilizing genetically barcoded virus technology, we show these natural killer cells efficiently reduced viral clones rebounding from latency. Moreover, a kick and kill strategy comprised of the protein kinase C modulator and latency reversing agent SUW133 and allogeneic human peripheral blood natural killer cells during anti-retroviral therapy eliminated the viral reservoir in a subset of mice. Therefore, combinations utilizing latency reversal agents with targeted cellular killing agents may be an effective approach to eradicating the viral reservoir. Here, Kim et al. describe a new kick and kill strategy utilizing a single administration of a protein kinase C modulator and latency reversing agent in combination with injections of allogeneic peripheral blood natural killer cells diminishes the HIV reservoir in HIV-infected humanized mice.
【저자키워드】 Viral reservoirs, HIV infections, 【초록키워드】 HIV, virus, Peripheral blood, Protein, Viremia, mice, persistence, HIV-1, Allogeneic, latency, HIV infection, cellular, natural killer cell, Combination, administration, Viral reservoir, infected cells, injection, previous study, clone, killing, humanized, approach, effective, Cell, shown, reduced, reduce, subset, inhibiting, diminishe, kill, anti-retroviral therapy, eliminated, 【제목키워드】 HIV, in vivo, natural killer cell,