Human cytomegalovirus entry into dendritic cells occurs via a macropinocytosis-like pathway in a pH-independent and cholesterol-dependent manner.
Human cytomegalovirus entry into dendritic cells occurs via a macropinocytosis-like pathway in a pH-independent and cholesterol-dependent manner.
复制标题
DOI：
10.1371/journal.pone.0034795
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Halary F
中科院分区：
文献类型：
--
作者：
Haspot F;Lavault A;Sinzger C;Laib Sampaio K;Stierhof YD;Pilet P;Bressolette-Bodin C;Halary F
人巨细胞病毒（HCMV）是一种普遍存在的疱疹病毒，能够感染成纤维细胞、上皮细胞、内皮细胞和造血细胞。在过去的十年中，一些研究小组提供了直接证据表明树突状细胞（DC）完全支持HCMV裂解周期。我们以前证明，C型凝集素树突状细胞特异性细胞间粘附分子-3-抓取非整联蛋白（DC-SIGN）在单核细胞衍生的DC（MDDC）上的HCMV对接中具有突出的作用。DC-SIGN/HCMV相互作用被证明是一个关键的早期事件，它大大增强了反式感染，即，从一个携带CMV的细胞到另一个未感染的细胞（或转感染），并使易感细胞完全允许HCMV感染。然而，关于HCMV如何进入MDDC还不清楚。在这项研究中，我们证明，VHL/E HCMV病毒粒子（内皮细胞/树突状细胞株）首先内化到MDDC的巨胞饮样过程中的肌动蛋白和胆固醇依赖性，但pH值无关的方式。我们观察到病毒体在具有内体特征的大的未涂覆囊泡中的积累，并且病毒体保持为完整的颗粒，其保留感染潜力数小时。这种转感染特性对MDDC是特异性的，因为单核细胞衍生的巨噬细胞或来自同一供体的单核细胞不能允许病毒的积累和随后的传播。总之，这些数据使我们能够描绘的早期机制的内化和进入的内皮细胞/树突状细胞的HCMV株进入人MDDC，并提出，DC可以作为一个“特洛伊木马”传达CMV从入口网站到其他位置，可能有利于潜伏期或急性感染的发生。
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that is able to infect fibroblastic, epithelial, endothelial and hematopoietic cells. Over the past ten years, several groups have provided direct evidence that dendritic cells (DCs) fully support the HCMV lytic cycle. We previously demonstrated that the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) has a prominent role in the docking of HCMV on monocyte-derived DCs (MDDCs). The DC-SIGN/HCMV interaction was demonstrated to be a crucial and early event that substantially enhanced infection in trans, i.e., from one CMV-bearing cell to another non-infected cell (or trans-infection), and rendered susceptible cells fully permissive to HCMV infection. Nevertheless, nothing is yet known about how HCMV enters MDDCs. In this study, we demonstrated that VHL/E HCMV virions (an endothelio/dendrotropic strain) are first internalized into MDDCs by a macropinocytosis-like process in an actin- and cholesterol-dependent, but pH-independent, manner. We observed the accumulation of virions in large uncoated vesicles with endosomal features, and the virions remained as intact particles that retained infectious potential for several hours. This trans-infection property was specific to MDDCs because monocyte-derived macrophages or monocytes from the same donor were unable to allow the accumulation of and the subsequent transmission of the virus. Together, these data allowed us to delineate the early mechanisms of the internalization and entry of an endothelio/dendrotropic HCMV strain into human MDDCs and to propose that DCs can serve as a "Trojan horse" to convey CMV from entry sites to other locations that may favor the occurrence of either latency or acute infection.
登录
查看更多内容
影响因子：
20.3
作者：
Dominguez-Soto, Angeles;Aragoneses-Fenoll, Laura;Corbi, Angel L.
通讯作者：
Corbi, Angel L.
DOI：
10.1073/pnas.0406821101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Feire, AL;Koss, H;Compton, T
通讯作者：
Compton, T
影响因子：
64.5
作者：
Marsh M;Helenius A
通讯作者：
Helenius A
DOI：
10.1083/jcb.124.5.689
发表时间：
1994-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hewlett LJ;Prescott AR;Watts C
通讯作者：
Watts C
影响因子：
5.5
作者：
Fleetwood, Andrew J.;Dinh, Hang;Hamilton, John A.
通讯作者：
Hamilton, John A.