Entry of viral capsids into the nucleus induces the formation of biomolecular condensates called HIV-1 membraneless organelles (HIV-1-MLOs). Several questions remain about their persistence, in vivo formation, composition, and function. Our study reveals that HIV-1-MLOs persisted for several weeks in infected cells, and their abundance correlated with viral infectivity. Using an appropriate animal model, we show that HIV-1-MLOs were formed in vivo during acute infection. To explore the viral structures present within these biomolecular condensates, we used a combination of double immunogold labeling, electron microscopy and tomography, and unveiled a diverse array of viral core structures. Our functional analyses showed that HIV-1-MLOs remained stable during treatment with a reverse transcriptase inhibitor, maintaining the virus in a dormant state. Drug withdrawal restored reverse transcription, promoting efficient virus replication akin to that observed in latently infected patients on antiretroviral therapy. However, when HIV-1 MLOs were deliberately disassembled by pharmacological treatment, we observed a complete loss of viral infectivity. Our findings show that HIV-1 MLOs shield the final reverse transcription product from host immune detection.

中文翻译：

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体内 HIV-1 核凝聚物可防止 cGAS 并允许逆转录。


病毒衣壳进入细胞核会诱导生物分子凝聚物的形成，称为 HIV-1 无膜细胞器 （HIV-1-MLO）。关于它们的持久性、体内形成、组成和功能仍然存在几个问题。我们的研究表明，HIV-1-MLOs 在受感染的细胞中持续存在数周，其丰度与病毒传染性相关。使用适当的动物模型，我们表明 HIV-1-MLOs 是在急性感染期间在体内形成的。为了探索这些生物分子凝聚物中存在的病毒结构，我们结合使用了双重免疫金标记、电子显微镜和断层扫描，并揭示了多种病毒核心结构。我们的功能分析表明，HIV-1-MLOs 在用逆转录酶抑制剂治疗期间保持稳定，使病毒维持在休眠状态。药物戒断恢复了逆转录，促进了有效的病毒复制，类似于在接受抗逆转录病毒治疗的潜伏感染患者中观察到的病毒复制。然而，当 HIV-1 MLO 通过药物治疗被故意分解时，我们观察到病毒传染性完全丧失。我们的研究结果表明，HIV-1 MLO 保护最终的逆转录产物免受宿主免疫检测。