Background HIV-1 promotes the formation of tunneling nanotubes (TNTs) that connect distant cells, aiding cell-to-cell viral transmission between macrophages. Our recent study suggests that the cellular protein M-Sec plays a role in these processes. However, the timing, mechanism, and to what extent M-Sec contributes to HIV-1 transmission is not fully understood, and the lack of a cell line model that mimics macrophages has hindered in-depth analysis. Results We found that HIV-1 increased the number, length and thickness of TNTs in a manner dependent on its pathogenic protein Nef and M-Sec in U87 cells, as observed in macrophages. In addition, we found that M-Sec was required not only for TNT formation but also motility of U87 cells, both of which are beneficial for viral transmission. In fact, M-Sec knockdown in U87 cells led to a significantly delayed viral production in both cellular and extracellular fractions. This inhibition was observed for wild-type virus, but not for a mutant virus lacking Nef, which is known to promote not only TNT formation but also migration of infected macrophages. Conclusions By taking advantage of useful features of U87 cells, we provided evidence that M-Sec mediates a rapid and efficient cell–cell transmission of HIV-1 at an early phase of infection by enhancing both TNT formation and cell motility.

中文翻译：

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M-Sec 通过多种机制促进 HIV-1 的细胞间传播

背景 HIV-1 促进隧道纳米管 (TNT) 的形成，这些纳米管连接远处的细胞，有助于巨噬细胞之间的细胞间病毒传播。我们最近的研究表明细胞蛋白 M-Sec 在这些过程中起作用。然而，尚未完全了解 M-Sec 对 HIV-1 传播的时间、机制和影响程度，并且缺乏模拟巨噬细胞的细胞系模型阻碍了深入分析。结果我们发现，如在巨噬细胞中所观察到的，HIV-1 以依赖于其在 U87 细胞中的致病蛋白 Nef 和 M-Sec 的方式增加了 TNT 的数量、长度和厚度。此外，我们发现 M-Sec 不仅是 TNT 形成所必需的，也是 U87 细胞运动所必需的，这两者都有利于病毒传播。实际上，U87 细胞中的 M-Sec 组合式导致细胞和细胞外部分的病毒产生显着延迟。对野生型病毒观察到这种抑制作用，但在缺乏 Nef 的突变病毒中观察不到这种抑制作用，众所周知，Nef 不仅促进 TNT 形成，而且促进受感染巨噬细胞的迁移。结论 通过利用 U87 细胞的有用特征，我们提供了证据，证明 M-Sec 通过增强 TNT 形成和细胞运动性，在感染早期介导 HIV-1 快速有效的细胞间传播。