While the microtubule end‐binding protein, EB1 facilitates early stages of HIV‐1 infection, how it does so remains unclear. Here, we show that beyond its effects on microtubule acetylation, EB1 also indirectly contributes to infection by delivering the plus‐end tracking protein (+TIP), cytoplasmic linker protein 170 (CLIP170) to the cell periphery. CLIP170 bound to intact HIV‐1 cores or in vitro assembled capsid–nucleocapsid complexes, while EB1 did not. Moreover, unlike EB1 and several other +TIPs, CLIP170 enhanced infection independently of effects on microtubule acetylation. Capsid mutants and imaging revealed that CLIP170 bound HIV‐1 cores in a manner distinct from currently known capsid cofactors, influenced by pentamer composition or curvature. Structural analyses revealed an EB‐like +TIP‐binding motif within the capsid major homology region (MHR) that binds SxIP motifs found in several +TIPs, and variability across this MHR sequence correlated with the extent to which different retroviruses engage CLIP170 to facilitate infection. Our findings provide mechanistic insights into the complex roles of +TIPs in mediating early stages of retroviral infection, and reveal divergent capsid‐based EB1 mimicry across retroviral species.

中文翻译：

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HIV-1 衣壳模仿微管调节器来协调感染的早期阶段。

虽然微管末端结合蛋白 EB1 促进 HIV-1 感染的早期阶段，但它如何做到这一点仍不清楚。在这里，我们表明，除了对微管乙酰化的影响外，EB1 还通过将正端跟踪蛋白 (+TIP)、细胞质接头蛋白 170 (CLIP170) 传递到细胞外周间接促进感染。CLIP170 结合完整的 HIV-1 核心或在体外组装的衣壳-核衣壳复合物，而 EB1 没有。此外，与 EB1 和其他几种 +TIP 不同，CLIP170 增强了感染，而与对微管乙酰化的影响无关。衣壳突变体和成像显示 CLIP170 结合 HIV-1 核心的方式与目前已知的衣壳辅因子不同，受五聚体组成或曲率的影响。结构分析揭示了衣壳主要同源区 (MHR) 内的 EB 样 +TIP 结合基序，该基序与多个 +TIP 中发现的 SxIP 基序结合，并且该 MHR 序列的变异性与不同逆转录病毒参与 CLIP170 以促进感染的程度相关. 我们的研究结果为 +TIP 在介导逆转录病毒感染的早期阶段的复杂作用提供了机制上的见解，并揭示了逆转录病毒物种之间不同的基于衣壳的 EB1 模拟。