Department of Medicine, Penn State College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
J Mol Biol. 2011 Jul 22;410(4):553-64. doi: 10.1016/j.jmb.2011.04.072.
The MA (matrix) domain of the retroviral Gag polyprotein plays several critical roles during virus assembly. Although best known for targeting the Gag polyprotein to the inner leaflet of the plasma membrane for virus budding, recent studies have revealed that MA also contributes to selective packaging of the genomic RNA (gRNA) into virions. In this Review, we summarize recent progress in understanding how MA participates in genome incorporation. We compare the mechanisms by which the MA domains of different retroviral Gag proteins influence gRNA packaging, highlighting variations and similarities in how MA directs the subcellular trafficking of Gag, interacts with host factors and binds to nucleic acids. A deeper understanding of how MA participates in these diverse functions at different stages in the virus assembly pathway will require more detailed information about the structure of the MA domain within the full-length Gag polyprotein. In particular, it will be necessary to understand the structural basis of the interaction of MA with gRNA, host transport factors and membrane phospholipids. A better appreciation of the multiple roles MA plays in genome packaging and Gag localization might guide the development of novel antiviral strategies in the future.
逆转录病毒 Gag 多聚蛋白的 MA（基质）结构域在病毒组装过程中发挥了几个关键作用。尽管 MA 结构域最广为人知的功能是将 Gag 多聚蛋白靶向质膜的内叶以进行病毒出芽，但最近的研究表明，MA 还参与了基因组 RNA（gRNA）的选择性包装到病毒粒子中。在这篇综述中，我们总结了近年来对 MA 结构域参与基因组整合的机制的理解进展。我们比较了不同逆转录病毒 Gag 蛋白的 MA 结构域影响 gRNA 包装的机制，强调了 MA 指导 Gag 亚细胞运输、与宿主因子相互作用以及与核酸结合的方式中的差异和相似之处。更详细地了解 MA 如何在病毒组装途径的不同阶段参与这些不同的功能，需要更详细地了解全长 Gag 多聚蛋白中 MA 结构域的结构信息。特别是，需要了解 MA 与 gRNA、宿主运输因子和膜磷脂相互作用的结构基础。更好地理解 MA 在基因组包装和 Gag 定位中的多种作用，可能会为未来指导开发新的抗病毒策略提供指导。
