Vaccinia virus tropism for primary hematolymphoid cells is determined by restricted expression of a unique virus receptor
Vaccinia virus tropism for primary hematolymphoid cells is determined by restricted expression of a unique virus receptor
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DOI：
10.1128/jvi.79.16.10397-10407.2005
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发表时间：
2005-08-01
影响因子：
5.4
通讯作者：
Feinberg, MB
中科院分区：
文献类型：
--
作者：
Chahroudi, A;Chavan, R;Feinberg, MB
痘病毒假定的广泛取向阻碍了识别结合的细胞受体(S)和病毒决定簇(S)的尝试。关于痘病毒与原代人类细胞的结合和感染的详细研究尚未进行。特别是，靶细胞感染的决定因素以及感染对参与产生抗病毒免疫反应的细胞的影响尚不完全清楚。在这份报告中，我们显示痘苗病毒(W)对原代人血淋巴细胞的趋向性比以前认识到的更有限。我们证明，痘苗病毒优先感染抗原提呈细胞(树突状细胞、单核/巨噬细胞和B细胞)和激活的T细胞，但不感染静止的T细胞。激活的T细胞的感染是允许的，病毒复制活跃，并产生具有感染性的后代。对感染的敏感性是由一种细胞受体的限制性表达决定的，该受体在T细胞激活时被诱导从头开始，并可通过胰酶或链霉蛋白酶处理从细胞表面移除。在激活的T细胞上表达的W受体表现出独特的特征，这些特征将其与用于感染培养细胞系的受体区分开来。观察到的W的限制性趋向性可能对理解自然的痘病毒感染和免疫以及基于痘病毒的疫苗开发具有重要的影响。
The presumed broad tropism of poxviruses has stymied attempts to identify both the cellular receptor(s) and the viral determinant(s) for binding. Detailed studies of poxvirus binding to and infection of primary human cells have not been conducted. In particular, the determinants of target cell infection and the consequences of infection for cells involved in the generation of antiviral immune responses are incompletely understood. In this report, we show that vaccinia virus (W) exhibits a more restricted tropism for primary hematolymphoid human cells than has been previously recognized. We demonstrate that vaccinia virus preferentially infects antigen-presenting cells (dendritic cells, monocytes/macrophages, and B cells) and activated T cells, but not resting T cells. The infection of activated T cells is permissive, with active viral replication and production of infectious progeny. Susceptibility to infection is determined by restricted expression of a cellular receptor that is induced de novo upon T-cell activation and can be removed from the cell surface by either trypsin or pronase treatment. The W receptor expressed on activated T cells displays unique characteristics that distinguish it from the receptor used to infect cell lines in culture. The observed restricted tropism of W may have significant consequences for the understanding of natural poxvirus infection and immunity and for poxvirus-based vaccine development.