BST-2 controls T cell proliferation and exhaustion by shaping the early distribution of a persistent viral infection.
BST-2 controls T cell proliferation and exhaustion by shaping the early distribution of a persistent viral infection.
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DOI：
10.1371/journal.ppat.1007172
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发表时间：
2018-07
期刊：
影响因子：
6.7
通讯作者：
McGavern DB
中科院分区：
文献类型：
--
作者：
Urata S;Kenyon E;Nayak D;Cubitt B;Kurosaki Y;Yasuda J;de la Torre JC;McGavern DB
干扰素诱导蛋白 BST-2（或系链蛋白）通过抑制许多包膜病毒的释放，在先天抗病毒防御系统中发挥重要作用。因此，病毒已经进化出对抗这种蛋白质的抗病毒活性的策略。虽然 BST-2 阻止病毒传播的机制已经被明确，但人们对这种蛋白质如何在持久性建立过程中塑造早期病毒分布和针对病原体的免疫防御知之甚少。使用淋巴细胞脉络膜脑膜炎病毒（LCMV）感染模型，我们深入了解该蛋白质的体外抗病毒活性与体内免疫防御的比较。我们观察到 BST-2 适度减少了培养细胞中病毒粒子的产生，这与 BST-2 干扰 LCMV Z 蛋白介导的病毒出芽过程的能力有关。此外，LCMV不编码BST-2拮抗剂，并且病毒传播在组成型表达BST-2的细胞中没有受到显着限制。与培养细胞中这种非常温和的作用相反，BST-2 在体内控制 LCMV 方面发挥着至关重要的作用。在 BST-2 缺陷小鼠中，感染后早期，持续存在的 LCMV 菌株不再局限于脾边缘区，这导致 LCMV 特异性 T 细胞分布改变、T 细胞增殖/功能降低、血清中的病毒控制延迟以及大脑中的持续存在。这些数据表明，BST-2 对于塑造解剖分布和针对体内持续病毒感染的适应性免疫反应非常重要。 BST-2（或系链蛋白）是一种抗病毒蛋白，可抑制许多包膜病毒的释放和传播，并作为针对感染的先天免疫防御的一部分而上调。通过研究淋巴细胞脉络膜脑膜炎病毒 (LCMV) 感染模型，我们深入了解 BST-2 在病毒持久性建立过程中如何塑造早期病毒分布和针对病毒的免疫防御。我们还研究了细胞培养物中 BST-2 的抗病毒活性与该蛋白在 LCMV 感染小鼠（体内）中所发挥的免疫防御作用的比较。我们观察到，BST-2 仅通过干扰病毒出芽过程而适度影响培养细胞中 LCMV 的产生，但在体内控制 LCMV 中发挥着至关重要的作用。在缺乏 BST-2 的情况下，在感染后的早期时间点，持续存在的 LCMV 菌株无法有效地容纳在脾脏中，导致系统性抗病毒 T 细胞反应和病毒控制受损。这些数据表明，BST-2 对于塑造解剖分布和针对体内持续病毒感染的适应性免疫反应非常重要。
The interferon inducible protein, BST-2 (or, tetherin), plays an important role in the innate antiviral defense system by inhibiting the release of many enveloped viruses. Consequently, viruses have evolved strategies to counteract the anti-viral activity of this protein. While the mechanisms by which BST-2 prevents viral dissemination have been defined, less is known about how this protein shapes the early viral distribution and immunological defense against pathogens during the establishment of persistence. Using the lymphocytic choriomeningitis virus (LCMV) model of infection, we sought insights into how the in vitro antiviral activity of this protein compared to the immunological defense mounted in vivo. We observed that BST-2 modestly reduced production of virion particles from cultured cells, which was associated with the ability of BST-2 to interfere with the virus budding process mediated by the LCMV Z protein. Moreover, LCMV does not encode a BST-2 antagonist, and viral propagation was not significantly restricted in cells that constitutively expressed BST-2. In contrast to this very modest effect in cultured cells, BST-2 played a crucial role in controlling LCMV in vivo. In BST-2 deficient mice, a persistent strain of LCMV was no longer confined to the splenic marginal zone at early times post-infection, which resulted in an altered distribution of LCMV-specific T cells, reduced T cell proliferation / function, delayed viral control in the serum, and persistence in the brain. These data demonstrate that BST-2 is important in shaping the anatomical distribution and adaptive immune response against a persistent viral infection in vivo. BST-2 (or, tetherin) is an antiviral protein that inhibits the release and spread of many enveloped viruses and is upregulated as part of the innate immune defense against infections. By studying the lymphocytic choriomeningitis virus (LCMV) model of infection, we sought insights into how BST-2 shapes the early viral distribution and immunological defense against a virus during the establishment of persistence. We also studied how the antiviral activity of BST-2 in cell culture compared to the immunological defense mounted by this protein in LCMV-infected mice (in vivo). We observed that BST-2 only modestly affected the production of LCMV in cultured cells by interfering with the viral budding process, but played a crucial role in controlling LCMV in vivo. In the absence of BST-2, a persistent strain of LCMV was ineffectively contained in the spleen at early time points post-infection, resulting in impaired antiviral T cell responses and viral control systemically. These data demonstrate that BST-2 is important in shaping the anatomical distribution and adaptive immune response against a persistent viral infection in vivo.
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影响因子：
4.6
作者：
Gossa S;Nayak D;Zinselmeyer BH;McGavern DB
通讯作者：
McGavern DB
影响因子：
6.2
作者：
Kuhl, Bjoern D.;Cheng, Vicky;Wainberg, Mark A.;Liang, Chen
通讯作者：
Liang, Chen
DOI：
10.4049/jimmunol.1400490
发表时间：
2014-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Li SX;Barrett BS;Heilman KJ;Messer RJ;Liberatore RA;Bieniasz PD;Kassiotis G;Hasenkrug KJ;Santiago ML
通讯作者：
Santiago ML
影响因子：
3.3
作者：
Jones PH;Mehta HV;Maric M;Roller RJ;Okeoma CM
通讯作者：
Okeoma CM
BST-2/Tetherin及其病毒拮抗作用的抗病毒活性的结构基础。
影响因子：
5.2
作者：
Arias JF;Iwabu Y;Tokunaga K
通讯作者：
Tokunaga K