The human immunodeficiency virus type 1 (HIV-1) proteome is expressed from alternatively spliced and unspliced genomic RNAs. However, HIV-1 RNAs that are not fully spliced are perceived by the host machinery as defective and are retained in the nucleus. During late infection, HIV-1 bypasses this regulatory mechanism by expression of the Rev protein from a fully spliced mRNA. Once imported into the nucleus, Rev mediates the export of unprocessed HIV-1 RNAs to the cytoplasm, leading to the production of the viral progeny. While regarded as a canonical RNA export factor, Rev has also been linked to HIV-1 RNA translation, stabilization, splicing and packaging. However, Rev's functions beyond RNA export have remained poorly understood. Here, we revisit this paradigmatic protein, reviewing recent data investigating its structure and function. We conclude by asking: what remains unknown about this enigmatic viral protein?

人类免疫缺陷病毒 1 型 (HIV-1) 蛋白质组由选择性剪接和未剪接的基因组 RNA 表达。然而，未完全剪接的 HIV-1 RNA 会被宿主机器视为有缺陷并保留在细胞核中。在感染后期，HIV-1 通过从完全剪接的 mRNA 表达 Rev 蛋白来绕过这种调节机制。一旦输入细胞核，Rev 就会介导未加工的 HIV-1 RNA 输出到细胞质，从而产生病毒后代。Rev 被视为典型的 RNA 输出因子，同时也与 HIV-1 RNA 翻译、稳定、剪接和包装有关。然而，Rev 在 RNA 输出之外的功能仍然知之甚少。在这里，我们重新审视这种典型蛋白质，回顾研究其结构和功能的最新数据。最后我们要问：这种神秘的病毒蛋白还有哪些未知之处？