Therapeutic strategies that provide effective and broad‐spectrum neutralization against HIV-1 infection are highly desirable. Here, we investigate the potential of nanoengineered CD4⁺ T cell membrane-coated nanoparticles (TNP) to neutralize a broad range of HIV-1 strains. TNP displayed outstanding neutralizing breadth and potency; they neutralized all 125 HIV-1-pseudotyped viruses tested, including global subtypes/recombinant forms, and transmitted/founder viruses, with a geometric mean 80% inhibitory concentration (IC₈₀) of 819 μg ml⁻¹ (range, 72 to 8,570 μg ml⁻¹). TNP also selectively bound to and induced autophagy in HIV-1-infected CD4⁺ T cells and macrophages, while having no effect on uninfected cells. This TNP-mediated autophagy inhibited viral release and reduced cell-associated HIV-1 in a dose- and phospholipase D1-dependent manner. Genetic or pharmacological inhibition of autophagy ablated this effect. Thus, we can use TNP as therapeutic agents to neutralize cell-free HIV-1 and to target HIV-1 gp120-expressing cells to decrease the HIV-1 reservoir.

中文翻译：

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CD4 + T细胞模拟纳米粒子广泛中和HIV-1，并通过自噬抑制病毒复制。

提供有效且广谱的中和抗HIV-1感染的治疗策略是非常理想的。在这里，我们调查了纳米工程CD4 ⁺ T细胞膜包被的纳米颗粒（TNP）中和各种HIV-1菌株的潜力。TNP具有出色的中和广度和效力。它们中和所有125的HIV-1-假型病毒测试，包括全球亚型的/重组的形式，并且发送/创始人病毒，用几何平均值的80％抑制浓度（IC ₈₀的819） 微克毫升^-1（范围，72至8570微克ml ^-1）。TNP还选择性结合并诱导HIV-1感染的CD4 ⁺自噬T细胞和巨噬细胞，而对未感染的细胞没有影响。这种TNP介导的自噬以剂量和磷脂酶D1依赖性方式抑制病毒释放并减少与细胞相关的HIV-1。自噬的遗传或药理抑制作用消除了这种作用。因此，我们可以使用TNP作为治疗剂来中和无细胞的HIV-1，并靶向表达HIV-1 gp120的细胞以减少HIV-1的贮积。