Orthobunyaviruses include several recently emerging viruses of significant medical and veterinary importance. There is currently very limited understanding on what determines the host species range of these pathogens. In this study we discovered that BST-2/tetherin restricts orthobunyavirus replication in a host-specific manner. We show that viruses with human tropism (Oropouche virus and La Crosse virus) are restricted by sheep BST-2 but not by the human orthologue, while viruses with ruminant tropism (Schmallenberg virus and others) are restricted by human BST-2 but not by the sheep orthologue. We also show that BST-2 blocks orthobunyaviruses replication by reducing the amount of envelope glycoprotein into viral particles egressing from infected cells. This is the first study identifying a restriction factor that correlates with species susceptibility to orthobunyavirus infection. This work provides insight to help us dissect the adaptive changes that bunyaviruses require to cross the species barrier and emerge into new species.

中文翻译：

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对 BST-2 限制的敏感性与正布尼亚病毒宿主范围相关。

Orthobunyaviruses 包括几种最近出现的具有重要医学和兽医重要性的病毒。目前对决定这些病原体宿主物种范围的因素的了解非常有限。在这项研究中，我们发现 BST-2/tetherin 以宿主特异性方式限制正布尼亚病毒复制。我们表明具有人类嗜性的病毒（Oropouche 病毒和拉克罗斯病毒）受绵羊 BST-2 的限制，但不受人类直系同源物的限制，而具有反刍动物嗜性的病毒（Schmallenberg 病毒等）受人类 BST-2 的限制，但不受羊直系同源物。我们还表明，BST-2 通过减少从受感染细胞中排出的病毒颗粒中包膜糖蛋白的量来阻止正布尼亚病毒的复制。这是第一项确定与物种对正布尼亚病毒感染易感性相关的限制因素的研究。这项工作提供了洞察力，帮助我们剖析布尼亚病毒跨越物种屏障并出现新物种所需的适应性变化。