Viral Glycoproteins Group, The Pirbright Institute, Ash Rd, Guildford, Surrey GU24 0NF, UK.
Institute of Immunology and Immunotherapy, The University of Birmingham, Birmingham B15 2TT, UK.
Viruses. 2019 Jul 30;11(8):692. doi: 10.3390/v11080692.
The measles virus (MeV), a member of the genus , is an established pathogen of humans. A key feature of morbilliviruses is their ability to spread by virus-cell and cell-cell fusion. The latter process, which leads to syncytia formation in vitro and in vivo, is driven by the viral fusion (F) and haemagglutinin (H) glycoproteins. In this study, we demonstrate that MeV glycoproteins are sensitive to inhibition by bone marrow stromal antigen 2 (BST2/Tetherin/CD317) proteins. BST2 overexpression causes a large reduction in MeV syncytia expansion. Using quantitative cell-cell fusion assays, immunolabeling, and biochemistry we further demonstrate that ectopically expressed BST2 directly inhibits MeV cell-cell fusion. This restriction is mediated by the targeting of the MeV H glycoprotein, but not other MeV proteins. Using truncation mutants, we further establish that the C-terminal glycosyl-phosphatidylinositol (GPI) anchor of BST2 is required for the restriction of MeV replication in vitro and cell-cell fusion. By extending our study to the ruminant morbillivirus peste des petits ruminants virus (PPRV) and its natural host, sheep, we also confirm this is a broad and cross-species specific phenotype.
麻疹病毒（MeV）是副黏液病毒科麻疹病毒属的成员，是一种确定的人类病原体。副黏液病毒的一个关键特征是其通过病毒-细胞和细胞-细胞融合进行传播的能力。在后一种过程中，会导致体外和体内合胞体的形成，这是由病毒融合（F）和血凝素（H）糖蛋白驱动的。在这项研究中，我们证明了 MeV 糖蛋白对骨髓基质抗原 2（BST2/Tetherin/CD317）蛋白的抑制作用敏感。BST2 的过表达导致 MeV 合胞体的扩张大量减少。通过定量细胞-细胞融合测定、免疫标记和生物化学，我们进一步证明了异位表达的 BST2 直接抑制 MeV 细胞-细胞融合。这种限制是通过针对 MeV H 糖蛋白的靶向介导的，但不是其他 MeV 蛋白。通过使用截断突变体，我们进一步确定 BST2 的 C 末端糖基磷脂酰肌醇（GPI）锚对于体外限制 MeV 复制和细胞-细胞融合是必需的。通过将我们的研究扩展到反刍动物副黏液病毒绵羊肺腺瘤病毒（PPRV）及其天然宿主绵羊，我们还证实了这是一种广泛且跨物种特异性的表型。
