HSV-2 glycoprotein gD targets the CC domain of tetherin and promotes tetherin degradation via lysosomal pathway.
HSV-2 glycoprotein gD targets the CC domain of tetherin and promotes tetherin degradation via lysosomal pathway.
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HSV-2 糖蛋白 gD 靶向系链蛋白的 CC 结构域并通过溶酶体途径促进系链蛋白降解
DOI：
10.1186/s12985-016-0610-7
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发表时间：
2016-09-15
期刊：
影响因子：
4.8
通讯作者：
Hu Q
中科院分区：
文献类型：
--
作者：
Liu Y;Li M;Zhang D;Zhang M;Hu Q
研究背景单纯疱疹病毒2型（HSV-2）是生殖器疱疹的主要病因。我们以前证明了宿主病毒限制因子tetherin限制HSV-2的释放，并被几种HSV-2糖蛋白拮抗。然而，HSV-2糖蛋白介导的tetherin的抵消作用的潜在机制仍不清楚。在这项研究中，我们调查是否tetherin限制HSV-2的细胞间传播和HSV-2 gD介导的tetherin.MethodsInfectious中心测定的拮抗作用的机制被用来测试是否tetherin可以影响HSV-2的细胞间传播。进行免疫共沉淀测定以定位HSV-2 gD介导的下调所需的系链蛋白结构域。进行免疫荧光测定以检测溶酶体或蛋白酶体中的系链蛋白的积累。结果1）Tetherin抑制HSV-2的细胞间扩散; 2）HSV-2 gD与Tetherin的CC结构域特异性结合; 3）HSV-2 gD促进Tetherin进入溶酶体降解途径。反过来，HSV-2 gD靶向栓蛋白的CC结构域并促进其在溶酶体中的降解。这项研究的发现增加了我们对tetherin限制和病毒对策的理解。
BackgroundHSV-2 is the major cause of genital herpes. We previously demonstrated that the host viral restriction factor tetherin restricts HSV-2 release and is antagonized by several HSV-2 glycoproteins. However, the mechanisms underlying HSV-2 glycoproteins mediated counteraction of tetherin remain unclear. In this study, we investigated whether tetherin restricts the cell-to-cell spread of HSV-2 and the mechanisms underlying HSV-2 gD mediated antagonism of tetherin.MethodsInfectious center assays were used to test whether tetherin could affect cell-to-cell spread of HSV-2. Coimmunoprecipitation assays were performed to map the tetherin domains required for HSV-2 gD-mediated downregulation. Immunoflurence assays were performed to detect the accumulation of tetherin in lysosomes or proteasomes. All experiments were repeated for at least three times and the data were performed statistical analysis.Results1) Tetherin restricts cell-to-cell spread of HSV-2; 2) HSV-2 gD specifically interacts with the CC domain of tetherin; 3) HSV-2 gD promotes tetherin to the lysosomal degradation pathway.ConclusionsTetherin not only restricts HSV-2 release but also its cell-to-cell spread. In turn, HSV-2 gD targets the CC domain of tetherin and promotes its degradation in the lysosome. Findings in this study have increased our understanding of tetherin restriction and viral countermeasures.
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影响因子：
1
作者：
Janvier, Katy;Roy, Nicolas;Berlioz-Torrent, Clarisse
通讯作者：
Berlioz-Torrent, Clarisse
影响因子：
6.7
作者：
Casartelli N;Sourisseau M;Feldmann J;Guivel-Benhassine F;Mallet A;Marcelin AG;Guatelli J;Schwartz O
通讯作者：
Schwartz O
DOI：
10.1073/pnas.0907075106
发表时间：
2009-12-08
影响因子：
11.1
作者：
Gupta, Ravindra K.;Mlcochova, Petra;Towers, Greg J.
通讯作者：
Towers, Greg J.
影响因子：
5.4
作者：
Mansouri, Mandana;Viswanathan, Kasinath;Frueh, Klaus
通讯作者：
Frueh, Klaus
影响因子：
30.3
作者：
Goffinet, Christine;Allespach, Ina;Keppler, Oliver T.
通讯作者：
Keppler, Oliver T.