HIV endocytosis after dendritic cell to T cell viral transfer leads to productive virus infection

HIV endocytosis after dendritic cell to T cell viral transfer leads to productive virus infection
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DOI:
10.1016/j.antiviral.2009.03.009
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发表时间:
2009-07-01
期刊:
影响因子:
7.6
通讯作者:
Este, Jose A.
Este, Jose A.
中科院分区:
医学2区
文献类型:
--
作者:
Clotet-Codina, Imma;Bosch, Berta;Este, Jose A.

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产生 HIV 的 T 细胞和初级 CD4+ T 细胞之间的接触可能会诱导靶细胞摄取 HIV,这些靶细胞被内吞到胰蛋白酶抗性区室中。我们现在比较了病毒从 T 细胞到 T 细胞的传播机制与受感染的树突状细胞 (DC) 到 T 细胞的传播机制。在 HIV-1 感染的 DC 与原代 CD4+ T 细胞的共培养中,病毒向靶细胞的传播对胰蛋白酶治疗具有抵抗力,只能通过抗 SUgp120 抗体 IgGb12 来阻止,而不能通过 TAK-779、C34 或 AZT 来阻止。重要的是,用 PHA/IL-2 刺激纯化的 HIV-1 负载 CD4+ T 细胞后,根据细胞内 CAp24 染色和细胞上清液中抗原测定的结果,细胞被有效感染。这些结果表明,在针对 HIV-1 进入或宿主免疫系统的药物存在的情况下,病毒内吞转移可能代表一种逃逸机制。 (C) 2009 Elsevier B.V. 保留所有权利。
Contacts between HIV-producing T cells and primary CD4+ T cells may induce the uptake of HIV by target cells that are endocytosed into trypsin-resistant compartments. We have now compared the mechanism of virus transmission from T cell-to-T cell versus infected dendritic cells (DCs)-to-T cell. In cocultures of HIV-1-infected DCs with primary CD4+ T cells, virus transmission to the target cells was resistant to trypsin treatment and could only be prevented by the anti-SUgp120 antibody IgGb12 but not by TAK-779, C34 or AZT. Importantly, upon stimulation of purified HIV-1-loaded CD4+ T cells with PHA/IL-2, cells became productively infected as measured by intracellular CAp24 staining and antigen determination in the cell supernatant. These results suggest that the viral endocytic transfer may represent a escape mechanism in the presence of drugs targeting HIV-1 entry or the host immune system. (C) 2009 Elsevier B.V. All rights reserved.