Anti-Tetherin Activities of HIV-1 Vpu and Ebola Virus Glycoprotein Do Not Involve Removal of Tetherin from Lipid Rafts

Anti-Tetherin Activities of HIV-1 Vpu and Ebola Virus Glycoprotein Do Not Involve Removal of Tetherin from Lipid Rafts
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DOI:
10.1128/jvi.06280-11
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发表时间:
2012-05-01
影响因子:
5.4
通讯作者:
Cannon, Paula M.
Cannon, Paula M.
中科院分区:
医学2区
文献类型:
--
作者:
Lopez, Lisa A.;Yang, Su Jung;Cannon, Paula M.

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BST-2/tetherin是一种干扰素诱导的宿主限制因子,可阻断新形成的包膜病毒的释放。它富含脂筏膜微区,这也是几种包膜病毒的组装位点。病毒抗栓蛋白因子,如HIV-1 Vpu蛋白,通常通过从细胞表面去除栓蛋白起作用。相比之下,埃博拉病毒糖蛋白(GP)是不寻常的,因为它阻断了拴蛋白的限制,而没有明显改变其细胞表面定位。我们探讨了GP的行为,以排除tetherin从特定的网站的病毒组装,而不公开地将其从细胞表面和脂筏排斥的可能性是参与的机制。然而,我们发现GP和Vpu对脂筏结构域中的Tetherin分布都没有任何影响。此外,GP没有阻止栓蛋白和出芽病毒颗粒的共定位。与以前的报道相反,我们也没有发现GP本身是筏蛋白的证据。总之,我们的数据表明,从脂筏中排除拴蛋白不是HIV-1 Vpu或埃博拉病毒GP用于抵消拴蛋白限制的机制。
BST-2/tetherin is an interferon-inducible host restriction factor that blocks the release of newly formed enveloped viruses. It is enriched in lipid raft membrane microdomains, which are also the sites of assembly of several enveloped viruses. Viral anti-tetherin factors, such as the HIV-1 Vpu protein, typically act by removing tetherin from the cell surface. In contrast, the Ebola virus glycoprotein (GP) is unusual in that it blocks tetherin restriction without apparently altering its cell surface localization. We explored the possibility that GP acts to exclude tetherin from the specific sites of virus assembly without overtly removing it from the cell surface and that lipid raft exclusion is the mechanism involved. However, we found that neither GP nor Vpu had any effect on tetherin's distribution within lipid raft domains. Furthermore, GP did not prevent the colocalization of tetherin and budding viral particles. Contrary to previous reports, we also found no evidence that GP is itself a raft protein. Together, our data indicate that the exclusion of tetherin from lipid rafts is not the mechanism used by either HIV-1 Vpu or Ebola virus GP to counteract tetherin restriction.