Varicella-zoster virus infection of human dendritic cells and transmission to T cells: Implications for virus dissemination in the host
Varicella-zoster virus infection of human dendritic cells and transmission to T cells: Implications for virus dissemination in the host
复制标题
DOI：
10.1128/jvi.75.13.6183-6192.2001
复制
发表时间：
2001-07-01
影响因子：
5.4
通讯作者：
Slobedman, B
中科院分区：
文献类型：
--
作者：
Abendroth, A;Morrow, G;Slobedman, B
在原发性水痘带状疱疹病毒（VZV）感染期间，据推测病毒从粘膜部位传播到局部淋巴结，在那里T细胞被感染。负责VZV从粘膜运输到淋巴结的细胞类型尚未确定。在本研究中，我们评估了人单核细胞来源的树突状细胞对VZV感染的敏感性，树突状细胞接种VZV Schenke株，并通过流式细胞术评估VZV和树突状细胞（CD 1a）抗原的表达。在5个重复实验中，34.4% +/- 6.6%（平均值+/- SEM）的CD 1a（+）细胞也为VZV抗原阳性。通过检测CD 1a（+）树突状细胞中的立即早期（IE62）、早期（ORF 29）和晚期（gC）基因产物，也显示树突状细胞对VZV感染敏感。从感染的树突状细胞回收感染性病毒，并且需要细胞-细胞接触来将病毒传播到允许的成纤维细胞，VZV感染的树突状细胞显示细胞活力或凋亡的证据没有显着下降，并没有表现出改变细胞表面的主要组织相容性复合物（MHC）I类，MHC II类，CD 86，CD 40，或CD 1a的水平。值得注意的是，当自体T淋巴细胞与VZV感染的树突状细胞孵育时，在CD 3（+）T淋巴细胞中很容易检测到VZV抗原，并且从这些细胞中回收感染性病毒。这些数据提供了树突状细胞对VZV是允许的并且树突状细胞感染可以导致病毒向T淋巴细胞的传播的第一证据。这些发现对我们理解VZV在原发性感染过程中如何传播具有重要意义。
During primary varicella-zoster virus (VZV) infection, it is presumed that virus is transmitted from mucosal sites to regional lymph nodes, where T cells become infected. The cell type responsible for VZV transport from the mucosa to the lymph nodes has not been defined. In this study, we assessed the susceptibility of human monocyte-derived dendritic cells to infection with VZV, Dendritic cells were inoculated with the VZV strain Schenke and assessed by flow cytometry for VZV and dendritic cell (CD1a) antigen expression. In five replicate experiments, 34.4% +/- 6.6% (mean +/- SEM) of CD1a(+) cells were also VZV antigen positive. Dendritic cells were also shown to be susceptible to VZV infection by the detection of immediate-early (IE62), early (ORF29), and late (gC) gene products in CD1a(+) dendritic cells, Infectious virus was recovered from infected dendritic cells, and cell-to-cell contact was required for transmission of virus to permissive fibroblasts, VZV-infected dendritic cells showed no significant decrease in cell viability or evidence of apoptosis and did not exhibit altered cell surface levels of major histocompatibility complex (MHC) class I, MHC class II, CD86, CD40, or CD1a. Significantly, when autologous T lymphocytes were incubated with VZV-infected dendritic cells, VZV antigens were readily detected in CD3(+) T lymphocytes and infectious virus was recovered from these cells. These data provide the first evidence that dendritic cells are permissive to VZV and that dendritic cell infection can lead to transmission of virus to T lymphocytes. These findings have implications for our understanding of how virus may be disseminated during primary VZV infection.