Bone marrow stromal cell antigen-2 (BST-2), also known as tetherin, is an interferon-inducible membrane-associated protein. It effectively targets enveloped viruses at the release step of progeny viruses from host cells, thereby restricting the further spread of viral infection. Junin virus (JUNV) is a member of Arenaviridae, which causes Argentine haemorrhagic fever that is associated with a high rate of mortality. In this study, we examined the effect of human BST-2 on the replication and propagation of JUNV. The production of JUNV Z-mediated virus-like particles (VLPs) was significantly inhibited by over-expression of BST-2. Electron microscopy analysis revealed that BST-2 functions by forming a physical link that directly retains VLPs on the cell surface. Infection using JUNV showed that infectious JUNV production was moderately inhibited by endogenous or exogenous BST-2. We also observed that JUNV infection triggers an intense interferon response, causing an upregulation of BST-2, in infected cells. However, the expression of cell surface BST-2 was reduced upon infection. Furthermore, the expression of JUNV nucleoprotein (NP) partially recovered VLP production from BST-2 restriction, suggesting that the NP functions as an antagonist against antiviral effect of BST-2. We further showed that JUNV NP also rescued the production of Ebola virus VP40-mediated VLP from BST-2 restriction as a broad spectrum BST-2 antagonist. To our knowledge, this is the first report showing that an arenavirus protein counteracts the antiviral function of BST-2.

中文翻译：

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人BST-2 / etherinin抑制Junin病毒从宿主细胞中释放，其抑制作用被病毒核蛋白部分抵消。

骨髓基质细胞抗原2（BST-2），也称为tetherin，是一种干扰素诱导的膜相关蛋白。它在子代病毒从宿主细胞释放的步骤中有效地靶向包膜病毒，从而限制了病毒感染的进一步传播。Junin病毒（JUNV）是Arenaviridae的成员，会导致阿根廷出血热，并伴有高死亡率。在这项研究中，我们检查了人类BST-2对JUNV复制和繁殖的影响。BST-2的过表达显着抑制了JUNV Z介导的病毒样颗粒（VLP）的产生。电子显微镜分析表明，BST-2通过形成直接将VLP保留在细胞表面的物理连接而起作用。使用JUNV的感染表明，感染性JUNV的产生受到内源性或外源性BST-2的中等抑制。我们还观察到在感染的细胞中，JUNV感染会触发强烈的干扰素反应，导致BST-2上调。但是，感染后细胞表面BST-2的表达降低。此外，JUNV核蛋白（NP）的表达部分地从BST-2限制中恢复了VLP的产生，这表明NP可以作为对抗BST-2抗病毒作用的拮抗剂。我们进一步表明，JUNV NP还以广谱BST-2拮抗剂的形式从BST-2限制中拯救了埃博拉病毒VP40介导的VLP的产生。据我们所知，这是第一个报告，表明一种沙门氏菌病毒蛋白抵消了BST-2的抗病毒功能。