DataSheet_1_Targeting HIV-1 reservoirs in T cell subsets.pdf

The HIV-1 reservoirs harbor the latent proviruses that are integrated into the host genome. It is a challenging task to eradicate the proviruses in order to achieve an HIV cure. We have described a strategy for the clearance of HIV-1 infection through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and promotion of apoptosis during viral re-activation. HIV-1 can infect various CD4+ T cell subsets, but it is not known whether the SECH approach is equally effective in targeting HIV-1 reservoirs in these different subsets in vivo. In a humanized mouse model, we found that treatments of HIV-1 infection by suppressive antiretroviral therapy (ART) led to the establishment of latent HIV reservoirs in naïve, central memory and effector memory T cells. Moreover, SECH treatments could clear latent HIV-1 reservoirs in these different T cell subsets of humanized mice. Co-culture studies showed that T cell subsets latently infected by HIV-1, but not uninfected bystander cells, were susceptible to cell death induced by SECH treatments. Our study suggests that the SECH strategy is effective for specific targeting of latent HIV-1 reservoirs in different T cell subsets.

HIV-1潜伏病毒库中存在整合于宿主基因组的潜伏前病毒。根除这类前病毒以实现HIV治愈，是一项极具挑战性的任务。我们此前报道了一种通过选择性清除携带复制型HIV的宿主细胞（SECH）来清除HIV-1感染的策略：在病毒再激活过程中抑制自噬并促进细胞凋亡。HIV-1可感染多种CD4+ T细胞亚群，但目前尚不清楚SECH策略在体内靶向这些不同亚群中的HIV-1潜伏病毒库时，是否能达到同等的清除效果。在人源化小鼠模型中，我们发现，通过抑制性抗逆转录病毒疗法（ART）治疗HIV-1感染后，可在初始T细胞、中枢记忆T细胞以及效应记忆T细胞中建立HIV潜伏病毒库。此外，SECH治疗可清除人源化小鼠体内这些不同T细胞亚群中的HIV-1潜伏病毒库。共培养实验结果显示，感染了HIV-1的潜伏感染T细胞亚群（而非未感染的旁观者细胞）对SECH治疗诱导的细胞死亡具有易感性。本研究表明，SECH策略可特异性靶向不同T细胞亚群中的HIV-1潜伏病毒库，具有良好的清除效果。