Infectious Lassa Virus, but Not Filoviruses, Is Restricted by BST-2/Tetherin
Infectious Lassa Virus, but Not Filoviruses, Is Restricted by BST-2/Tetherin
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DOI：
10.1128/jvi.00103-10
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发表时间：
2010-10-01
影响因子：
5.4
通讯作者：
Bavari, Sina
中科院分区：
文献类型：
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作者：
Radoshitzky, Sheli R.;Dong, Lian;Bavari, Sina
骨髓基质抗原2（BST-2/tetherin）是一种抑制HIV-1释放的细胞膜蛋白。我们首次使用感染性病毒表明，BST-2也抑制沙粒病毒的外出，但对丝状病毒的复制和传播没有影响。具体而言，感染性拉沙病毒（LASV）的释放显着减少或增加的人细胞中，BST-2的稳定表达或敲除，分别。相反，传染性扎伊尔埃博拉病毒（ZEBOV）和维多利亚湖马尔堡病毒（MARV）的复制和传播不受这些条件的影响。传染性裂谷热病毒（RVFV）和牛痘病毒（CPXV）的复制也不受BST-2表达的影响。人或鼠BST-2的细胞水平升高可抑制病毒样颗粒（VLP）的释放，VLP由多种高毒力NIAID优先病原体的基质蛋白组成，包括沙粒病毒（LASV和马丘波病毒[MACV]）、丝状病毒（ZEBOV和MARV）和副粘病毒（尼帕病毒）。尽管丝状病毒的糖蛋白在VLP的情况下抵消了BST-2的抗病毒活性，但它们无法在BST-2过表达时拯救沙粒病毒（LASV和MACV）VLP的释放。此外，我们没有观察到丝状病毒糖蛋白与BST-2在感染真实病毒期间的共定位。在BST-2的存在下，没有一种沙粒病毒编码的蛋白质拯救了VLP的出芽。我们的研究结果表明，BST-2可能是一个广泛的抗病毒因子，能够限制各种各样的人类病原体的释放。然而，至少丝状病毒、RVFV和CPXV对其抑制作用免疫。
Bone marrow stromal antigen 2 (BST-2/tetherin) is a cellular membrane protein that inhibits the release of HIV-1. We show for the first time, using infectious viruses, that BST-2 also inhibits egress of arenaviruses but has no effect on filovirus replication and spread. Specifically, infectious Lassa virus (LASV) release significantly decreased or increased in human cells in which BST-2 was either stably expressed or knocked down, respectively. In contrast, replication and spread of infectious Zaire ebolavirus (ZEBOV) and Lake Victoria marburgvirus (MARV) were not affected by these conditions. Replication of infectious Rift Valley fever virus (RVFV) and cowpox virus (CPXV) was also not affected by BST-2 expression. Elevated cellular levels of human or murine BST-2 inhibited the release of virus-like particles (VLPs) consisting of the matrix proteins of multiple highly virulent NIAID Priority Pathogens, including arenaviruses (LASV and Machupo virus [MACV]), filoviruses (ZEBOV and MARV), and paramyxoviruses (Nipah virus). Although the glycoproteins of filoviruses counteracted the antiviral activity of BST-2 in the context of VLPs, they could not rescue arenaviral (LASV and MACV) VLP release upon BST-2 overexpression. Furthermore, we did not observe colocalization of filoviral glycoproteins with BST-2 during infection with authentic viruses. None of the arenavirus-encoded proteins rescued budding of VLPs in the presence of BST-2. Our results demonstrate that BST-2 might be a broad antiviral factor with the ability to restrict release of a wide variety of human pathogens. However, at least filoviruses, RVFV, and CPXV are immune to its inhibitory effect.