Tetherin restricts productive HIV-1 cell-to-cell transmission.
Tetherin restricts productive HIV-1 cell-to-cell transmission.
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DOI：
10.1371/journal.ppat.1000955
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发表时间：
2010-06-17
期刊：
影响因子：
6.7
通讯作者：
Schwartz O
中科院分区：
文献类型：
--
作者：
Casartelli N;Sourisseau M;Feldmann J;Guivel-Benhassine F;Mallet A;Marcelin AG;Guatelli J;Schwartz O
IFN 诱导的抗病毒蛋白系链蛋白（或 BST-2/CD317/HM1.24）会损害受感染细胞释放成熟的 HIV-1 颗粒。 HIV-1 Vpu 拮抗 Tetherin 的作用。被困在细胞表面的病毒体的命运仍然知之甚少。在这里，我们询问 Tetherin 是否会损害 HIV 细胞间传播（病毒传播的主要方式）。感染野生型或ΔVpu HIV的Tetherin阳性或阴性细胞被用作供体细胞并与靶淋巴细胞共培养。我们发现，tetherin 抑制 ΔVpu 向目标细胞间的有效传播，并损害 WT HIV 的传播。 Tetherin 与 Gag 一起积聚在感染细胞和靶细胞之间的接触区，但不会阻止病毒突触的形成。在存在系链蛋白的情况下，病毒大多以异常大的斑块形式转移到目标。这些病毒聚集体在转移后不能有效促进感染，因为它们积聚在靶细胞表面并损害其融合能力。通过在供体细胞中印记病毒颗粒，Tetherin 是限制病毒细胞间传播的表面限制因子的第一个例子。 Tetherin 是一种细胞表面“限制因子”，起到先天抗病毒防御的作用。 Tetherin 可以防止新产生的 HIV-1 和其他包膜病毒颗粒从受感染细胞表面逸出。 HIV-1 编码蛋白质 Vpu 来抵消宿主的这种防御。我们在这里研究了捕获在细胞表面的 HIV-1 颗粒是否可能传播到邻近的未感染细胞。通过细胞间接触的直接传播确实是病毒传播的有效手段。受感染的供体细胞和靶细胞之间可能形成病毒突触，从而允许病毒快速大规模传播。我们发现，tetherin 抑制 Vpu 缺失的 HIV 向靶细胞的有效细胞间传播，并损害野生型病毒的传播。 Tetherin 与 Gag 一起积聚在感染细胞和靶细胞之间的接触区，但不会阻止病毒突触的形成。通过系链蛋白，病毒大多以异常大的斑块形式转移到目标，这些斑块的融合能力受到损害。这些结果代表了限制病毒细胞间传播的表面限制因子的第一个例子，它在供体细胞中起作用，但在病毒材料转移到新的受体细胞后抑制感染。
The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or ΔVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of ΔVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread. Tetherin is a cell surface “restriction factor” that acts as an innate antiviral defense. Tetherin prevents newly produced particles of HIV-1 and other enveloped viruses from escaping the surface of infected cells. HIV-1 encodes the protein Vpu to counteract this host defense. We have studied here if HIV-1 particles trapped at the cell surface may be transmitted to neighboring uninfected cells. Direct transmission through cell-to-cell contacts is indeed an efficient means for viral spread. Virological synapses may be formed between infected donor cells and target cells, allowing rapid and massive transmission of viruses. We show that tetherin inhibits productive cell-to-cell transmission of Vpu-deleted HIV to target cells, and impairs that of wild-type virus. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. With tetherin, viruses are then mostly transferred to targets as abnormally large patches that are impaired in their fusion capacities. These results represent the first example of a surface restriction factor limiting viral cell-to-cell spread, acting in donor cells, but inhibiting infection after transfer of viral material to novel recipient cells.
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DOI：
10.1073/pnas.0913650107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Groom, Harriet C. T.;Yap, Melvyn W.;Bishop, Kate N.
通讯作者：
Bishop, Kate N.
影响因子：
30.3
作者：
Goffinet, Christine;Allespach, Ina;Keppler, Oliver T.
通讯作者：
Keppler, Oliver T.
影响因子：
5.4
作者：
Müller, B;Daecke, J;Kräusslich, HG
通讯作者：
Kräusslich, HG
影响因子：
6.7
作者：
McNatt, Matthew W.;Zang, Trinity;Hatziioannou, Theodora;Bartlett, Mackenzie;Ben Fofana, Ismael;Johnson, Welkin E.;Neil, Stuart J. D.;Bieniasz, Paul D.
通讯作者：
Bieniasz, Paul D.
影响因子：
6.7
作者：
Gupta RK;Hué S;Schaller T;Verschoor E;Pillay D;Towers GJ
通讯作者：
Towers GJ