부산대학교 도서관

The presence of persistent, latent HIV reservoirs in [CD4.sup.+] T cells obstructs current efforts to cure infection. The so-called kick-and-kill paradigm proposes to purge these reservoirs by combining latency-reversing agents with immune effectors such as cytotoxic T lymphocytes. Support for this approach is largely based on success in latency models, which do not fully reflect the makeup of latent reservoirs in individuals on long-term antiretroviral therapy (ART). Recent studies have shown that [CD8.sup.+] T cells have the potential to recognize defective proviruses, which comprise the vast majority of all infected cells, and that the proviral landscape can be shaped over time due to in vivo clonal expansion of infected [CD4.sup.+] T cells. Here, we have shown that treating [CD4.sup.+] T cells from ART-treated individuals with combinations of potent latency-reversing agents and autologous [CD8.sup.+] T cells consistently reduced cell-associated HIV DNA, but failed to deplete replication-competent virus. These [CD8.sup.+] T cells recognized and potently eliminated [CD4.sup.+] T cells that were newly infected with autologous reservoir virus, ruling out a role for both immune escape and [CD8.sup.+] T cell dysfunction. Thus, our results suggest that cells harboring replication-competent HIV possess an inherent resistance to [CD8.sup.+] T cells that may need to be addressed to cure infection.
Introduction Eradicating latent HIV reservoirs will require the elimination of persistent populations of cells with integrated HIV proviruses. The major barrier impeding viral eradication is thought to be a reservoir [...]