Utilizing cytotoxic lymphocytes for indirect shock-and-kill strategy in HIV-1 treatment

Abstract: Despite the existence of a treatment, there is still not a cure for HIV-1 infection and there arearound 700 000 deaths per year from AIDS-related diseases. A major barrier for a cure is theestablishment of latent reservoirs that are impossible to distinguish from healthy cells and thuscan escape the immune system. One potential solution is called shock-and-kill strategy, whichaims to induce HIV-1 reactivation, exposing latently infected cells to the immune system andmaking them susceptible to cell death. In our lab, it was seen that when NK cells are stimulatedwith a pan-caspase inhibitor, they acquire the “shock” ability, but it is still unknown how. Inthis project, we observed that the supernatant from pan-caspase inhibitor-stimulated NK cellscan increase HIV-1 reactivation in two different latency models. Furthermore, the protein levelsof three HIV-1 suppressors were found to be increased in the same supernatant. For this reason,their effect in HIV-1 reactivation in latently infected cells was analysed. Although we did notobserve an increase in HIV-1 reactivation, the upregulation of these three proteins can be usefulin the clinical context. Since they are HIV-1 suppressors, their presence can prevent theinfection from spreading after latent cells are reactivated. Altogether, our results show that NKcells stimulated with a pan-caspase inhibitor are secreting a biological product that inducesHIV-1 reactivation. This indicates that there is a pathway in NK cells that can potentially beexploited in order for them to be able to induce HIV-1 reactivation.