Spatial Relationships between Markers for Secretory and Endosomal Machinery in Human Cytomegalovirus-Infected Cells versus Those in Uninfected Cells
Spatial Relationships between Markers for Secretory and Endosomal Machinery in Human Cytomegalovirus-Infected Cells versus Those in Uninfected Cells
复制标题
DOI：
10.1128/jvi.00155-11
复制
发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Pellett, Philip E.
中科院分区：
文献类型：
--
作者：
Das, Subhendu;Pellett, Philip E.
人巨细胞病毒（HCMV）诱导分泌器广泛重塑，形成细胞质病毒体组装区室（cVAC），在此发生病毒体覆盖和增殖。我们通过共聚焦显微镜研究了cVAC的结构，以评估与单个分泌细胞器特异性相关的蛋白质的三维分布。在感染的细胞中，早期内体抗原1（EEA 1）阳性囊泡集中在cVAC的中心，如前所述，与内质网，高尔基体和trans-Golgi网络（TGN）的标记物所显示的结构不同。EEA 1阳性囊泡可以与内体再循环标记物强烈相关，在较小程度上与转运III（ESCRT III）机制所需的内体分选复合物组分相关的标记物相关，然后与晚期内体标记物相关。在未感染和感染细胞的比较中，我们发现细胞器标记物的结构关联和共定位以及净细胞器体积发生了显着变化。这些结果提供了新的证据表明，HCMV诱导的膜转运装置的重塑涉及的不仅仅是简单的搬迁和扩展的预先存在的结构，并与假设一致，即在HCMV感染的细胞中的分泌细胞器的身份的转变导致新的功能配置文件。
Human cytomegalovirus (HCMV) induces extensive remodeling of the secretory apparatus to form the cytoplasmic virion assembly compartment (cVAC), where virion tegumentation and envelopment take place. We studied the structure of the cVAC by confocal microscopy to assess the three-dimensional distribution of proteins specifically associated with individual secretory organelles. In infected cells, early endosome antigen 1 (EEA1)-positive vesicles are concentrated at the center of the cVAC and, as previously seen, are distinct from structures visualized by markers for the endoplasmic reticulum, Golgi apparatus, and trans-Golgi network (TGN). EEA1-positive vesicles can be strongly associated with markers for recycling endosomes, to a lesser extent with markers associated with components of the endosomal sorting complex required for transport III (ESCRT III) machinery, and then with markers of late endosomes. In comparisons of uninfected and infected cells, we found significant changes in the structural associations and colocalization of organelle markers, as well as in net organelle volumes. These results provide new evidence that the HCMV-induced remodeling of the membrane transport apparatus involves much more than simple relocation and expansion of preexisting structures and are consistent with the hypothesis that the shift in identity of secretory organelles in HCMV-infected cells results in new functional profiles.