Infectious and whole inactivated simian immunodeficiency viruses interact similarly with primate dendritic cells (DCs): Differential intracellular fate of virions in mature and immature DCs
Infectious and whole inactivated simian immunodeficiency viruses interact similarly with primate dendritic cells (DCs): Differential intracellular fate of virions in mature and immature DCs
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DOI：
10.1128/jvi.76.6.2936-2951.2002
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发表时间：
2002-03-01
影响因子：
5.4
通讯作者：
Pope, M
中科院分区：
文献类型：
--
作者：
Frank, I;Piatak, M;Pope, M
作为人类免疫缺陷病毒 I 型和猿猴免疫缺陷病毒（HIV-1 和 SIV）的潜在靶标，树突状细胞 (DC) 可能在感染的发生和传播以及抗病毒免疫的诱导中发挥重要作用。使用SIV-猕猴系统来研究DC-病毒相互作用的早期事件，我们将具有构象和功能完整的包膜糖蛋白（2,2'-二硫二吡啶[AT-2] SIV）的化学灭活的SIV与感染性和热处理的SIV进行比较。人类和猕猴 DC 与 SIV 的相互作用相似，但对 DC 活力、表型或内吞功能没有可检测到的影响。通过测量细胞相关病毒 RNA 进行评估，DC 捕获了相当多的病毒，并且当病毒经过热处理或源自表达低水平包膜糖蛋白的病毒株时，捕获量会减少。 SIV 蛋白的免疫染色和电子显微镜表明，在内吞活性的未成熟 DC 的外围保留了很少的完整病毒颗粒。这与成熟 DC 内较深的大囊泡区室中大量病毒粒子的核周定位形成鲜明对比（其中巨胞饮作用下调）。未成熟和成熟的 DC 都能够通过网格蛋白包被的凹坑介导的 SIV 摄取，支持了成熟 DC 中很容易发生受体介导的病毒摄取的观点。虽然大量完整病毒优先在成熟 DC 中发现，但未成熟和成熟 DC 均含有相似数量的病毒 RNA，这表明不同的摄取/病毒进入机制在未成熟和成熟 DC 中活跃。这些发现对 HIV-1 和 SIV 的细胞间传播具有重要意义，并支持使用 AT-2 SIV（一种真实但非传染性的病毒形式）作为研究 DC 处理和呈递 AT-2 SIV 抗原的有用工具。
As potential targets for human immunodeficiency virus type I and simian immunodeficiency virus (HIV-1 and SIV), dendritic cells (DCs) likely play a significant role in the onset and spread of infection as well as in the induction of antiviral immunity. Using the SIV-macaque system to study the very early events in DC-virus interactions, we compared chemically inactivated SIV having conformationally and functionally intact envelope glycoproteins (2,2'-dithiodipyridine [AT-2] SIV) to infectious and heat-treated SIV. Both human and macaque DCs interact similarly with SIV without detectable effects on DC viability, phenotype, or endocytic function. As assessed by measuring cell-associated viral RNA, considerable amounts of virus are captured by the DCs and this is reduced when the virus is heat treated or derived from a strain that expresses low levels of envelope glycoprotein. Immunostaining for SIV proteins and electron microscopy indicated that few intact virus particles are retained at the periphery of the endocytically active, immature DCs. This contrasts with a perinuclear localization of numerous virions in large vesicular compartments deeper within mature DCs (in which macropinocytosis is down-regulated). Both immature and mature DCs are capable of clathrin-coated pit-mediated uptake of SIV, supporting the notion that the receptor-mediated uptake of virus can occur readily in mature DCs. While large numbers of whole viruses were preferentially found in mature DCs, both immature and mature DCs contained similar amounts of viral RNA, suggesting that different uptake/virus entry mechanisms are active in immature and mature DCs. These findings have significant implications for cell-to-cell transmission of HIV-1 and SIV and support the use of AT-2 SIV, an authentic but noninfectious form of virus, as a useful tool for studies of processing and presentation of AT-2 SIV antigens by DCs.