Lučin Pero, Kareluša Ljerka, Blagojević Zagorac Gordana, Mahmutefendić Lučin Hana, Pavišić Valentino, Jug Vučko Natalia, Lukanović Jurić Silvija, Marcelić Marina, Lisnić Berislav, Jonjić Stipan
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
University North - University Center Varaždin, Varaždin, Croatia.
Front Cell Dev Biol. 2018 Dec 4;6:165. doi: 10.3389/fcell.2018.00165. eCollection 2018.
Cytomegaloviruses (CMV) reorganize membranous system of the cell in order to develop a virion assembly compartment (VAC). The development starts in the early (E) phase of infection with the reorganization of the endosomal system and the Golgi and proceeds to the late phase until newly formed virions are assembled and released. The events in the E phase involve reorganization of the endosomal recycling compartment (ERC) in a series of cellular alterations that are mostly unknown. In this minireview, we discuss the effect of murine CMV infection on Rab proteins, master regulators of membrane trafficking pathways, which in the cascades with their GEFs and GAPs organize the flow of membranes through the ERC. Immunofluorescence analyzes of murine CMV infected cells suggest perturbations of Rab cascades that operate at the ERC. Analysis of cellular transcriptome in the course of both murine and human CMV infection demonstrates the alteration in expression of cellular genes whose products are known to build Rab cascades. These alterations, however, cannot explain perturbations of the ERC. Cellular proteome data available for human CMV infected cells suggests the potential role of RabGAP downregulation at the end of the E phase. However, the very early onset of the ERC alterations in the course of MCMV infection indicates that CMVs exploit Rab cascades to reorganize the ERC, which represents the earliest step in the sequential establishment of the cVAC.
巨细胞病毒（CMV）会重组细胞的膜系统，以形成病毒体装配区室（VAC）。这种发育始于感染的早期（E）阶段，此时内体系统和高尔基体开始重组，并持续到晚期，直至新形成的病毒体组装并释放。E阶段的事件包括内体循环区室（ERC）在一系列大多未知的细胞变化中进行重组。在这篇小型综述中，我们讨论了鼠巨细胞病毒感染对Rab蛋白的影响，Rab蛋白是膜运输途径的主要调节因子，它们与鸟嘌呤核苷酸交换因子（GEF）和GTP酶激活蛋白（GAP）一起在级联反应中组织通过ERC的膜流。对鼠巨细胞病毒感染细胞的免疫荧光分析表明，在ERC起作用的Rab级联反应受到了干扰。对鼠巨细胞病毒和人巨细胞病毒感染过程中细胞转录组的分析表明，已知其产物参与构建Rab级联反应的细胞基因的表达发生了改变。然而，这些改变无法解释ERC的扰动。可获得的人巨细胞病毒感染细胞的细胞蛋白质组数据表明，在E阶段末期RabGAP下调可能发挥作用。然而，在鼠巨细胞病毒感染过程中ERC改变的非常早期发生，这表明巨细胞病毒利用Rab级联反应来重组ERC，这是连续建立cVAC的最早步骤。
