Tetherin promotes the innate and adaptive cell-mediated immune response against retrovirus infection in vivo.
Tetherin promotes the innate and adaptive cell-mediated immune response against retrovirus infection in vivo.
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DOI：
10.4049/jimmunol.1400490
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发表时间：
2014-07-01
期刊：
影响因子：
--
通讯作者：
Santiago ML
中科院分区：
文献类型：
--
作者：
Li SX;Barrett BS;Heilman KJ;Messer RJ;Liberatore RA;Bieniasz PD;Kassiotis G;Hasenkrug KJ;Santiago ML
Tetherin/BST-2是一种宿主限制因子，通过将新生病毒粒子拴在质膜上，直接抑制逆转录病毒颗粒的释放。然而，Tetherin在逆转录病毒感染过程中的免疫学影响仍不清楚。我们现在证明Tetherin影响抗逆转录病毒细胞介导的免疫反应。与Tetherin的直接抗病毒作用不同，Tetherin依赖于细胞表面的表达，而免疫调节作用与分子的内吞作用有关。与编码内吞功能缺陷的NZW/LacJ Tetherin的小鼠相比，编码内吞功能正常的C57BL/6 Tetherin的小鼠在感染Friend逆转录病毒(FV)后7天表现出较低的病毒血症和病理学。值得注意的是，抗逆转录病毒保护与更强的NK细胞反应相关。此外，在感染后2周，野生型C57BL/6小鼠的FV感染水平显著低于Tetherin基因敲除小鼠，并且抗逆转录病毒保护与更强的NK细胞和病毒特异性CD8+T细胞反应相关。结果表明，Tetherin在体内对逆转录病毒感染的细胞免疫反应起到了调节剂的作用。
Tetherin/BST-2 is a host restriction factor that could directly inhibit retroviral particle release by tethering nascent virions to the plasma membrane. However, the immunological impact of Tetherin during retrovirus infection remains unknown. We now show that Tetherin influences antiretroviral cell-mediated immune responses. In contrast to the direct antiviral effects of Tetherin, which are dependent on cell surface expression, the immunomodulatory effects are linked to the endocytosis of the molecule. Mice encoding endocytosis-competent C57BL/6 Tetherin exhibited lower viremia and pathology at 7 days post-infection with Friend retrovirus (FV) compared to mice encoding endocytosis-defective NZW/LacJ Tetherin. Notably, antiretroviral protection correlated with stronger NK cell responses. In addition, FV infection levels were significantly lower in wild-type C57BL/6 mice than in Tetherin knock-out mice at 2 weeks post-infection, and antiretroviral protection correlated with stronger NK cell and virus-specific CD8+ T cell responses. The results demonstrate that Tetherin acts as a modulator of the cell-mediated immune response against retrovirus infection in vivo.
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