Architecture et Réactivité de l'ARN, UPR 9002, IBMC, CNRS, Université de Strasbourg, 2 allée Konrad Roentgen, CEDEX F-67084 Strasbourg, France.
Int J Mol Sci. 2021 Mar 11;22(6):2871. doi: 10.3390/ijms22062871.
Protein post-translational modifications (PTMs) play key roles in eukaryotes since they finely regulate numerous mechanisms used to diversify the protein functions and to modulate their signaling networks. Besides, these chemical modifications also take part in the viral hijacking of the host, and also contribute to the cellular response to viral infections. All domains of the human immunodeficiency virus type 1 (HIV-1) Gag precursor of 55-kDa (Pr55), which is the central actor for viral RNA specific recruitment and genome packaging, are post-translationally modified. In this review, we summarize the current knowledge about HIV-1 Pr55 PTMs such as myristoylation, phosphorylation, ubiquitination, sumoylation, methylation, and ISGylation in order to figure out how these modifications affect the precursor functions and viral replication. Indeed, in HIV-1, PTMs regulate the precursor trafficking between cell compartments and its anchoring at the plasma membrane, where viral assembly occurs. Interestingly, PTMs also allow Pr55 to hijack the cell machinery to achieve viral budding as they drive recognition between viral proteins or cellular components such as the ESCRT machinery. Finally, we will describe and compare PTMs of several other retroviral Gag proteins to give a global overview of their role in the retroviral life cycle.
蛋白质翻译后修饰（PTMs）在真核生物中起着关键作用，因为它们精细地调节了许多用于多样化蛋白质功能和调节其信号网络的机制。此外，这些化学修饰还参与了病毒对宿主的劫持，并有助于细胞对病毒感染的反应。人类免疫缺陷病毒 1 型（HIV-1）Gag 前体 55kDa（Pr55）的所有结构域都发生了翻译后修饰，该前体是病毒 RNA 特异性募集和基因组包装的核心因子。在这篇综述中，我们总结了 HIV-1 Pr55 PTMs 的最新知识，如豆蔻酰化、磷酸化、泛素化、SUMO 化、甲基化和 ISG 化，以了解这些修饰如何影响前体功能和病毒复制。事实上，在 HIV-1 中，PTMs 调节前体在细胞区室之间的运输及其在病毒装配发生的质膜上的锚定。有趣的是，PTMs 还允许 Pr55 劫持细胞机制以实现病毒出芽，因为它们驱动病毒蛋白或细胞成分（如 ESCRT 机制）之间的识别。最后，我们将描述和比较几种其他逆转录病毒 Gag 蛋白的 PTMs，以全面概述它们在逆转录病毒生命周期中的作用。
