Targeting HIV-1 reservoirs in T cell subsets.

Targeting HIV-1 reservoirs in T cell subsets.
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针对 T 细胞亚群中的 HIV-1 储存库。

DOI:
10.3389/fimmu.2023.1087923
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发表时间:
2023
影响因子:
7.3
通讯作者:
Wang, Jin
Wang, Jin
中科院分区:
医学2区
文献类型:
--
作者:
Li, Min;Budai, Marietta M.;Chen, Min;Wang, Jin

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相似文献

HIV-1储存库包含潜伏的前病毒,这些前病毒被整合到宿主基因组中。根除原病毒以实现治愈艾滋病毒是一项具有挑战性的任务。我们已经描述了一种清除HIV-1感染的策略,通过在病毒再激活过程中抑制自噬和促进细胞凋亡,选择性地消除宿主细胞携带复制能力强的HIV (SECH)。HIV-1可以感染各种CD4+ T细胞亚群,但目前尚不清楚SECH方法是否同样有效地靶向体内这些不同亚群中的HIV-1储存库。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感染导致在naïve、中枢记忆和效应记忆T细胞中建立潜伏的HIV库。此外,SECH治疗可以清除人源化小鼠这些不同T细胞亚群中的潜伏HIV-1储存库。共培养研究表明,潜伏感染HIV-1的T细胞亚群,而非未感染的旁观者细胞,易受SECH治疗诱导的细胞死亡。我们的研究表明,SECH策略对于特异性靶向不同T细胞亚群中的潜伏HIV-1库是有效的。
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.
DOI: 10.1002/jlb.4mr0222-606
发表时间: 2022-11
影响因子: 5.5
作者:
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在长期持久性中自噬的需求,而不是记忆B细胞的初始形成。
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影响因子: --
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