Functional expression and membrane fusion tropism of the envelope glycoproteins of Hendra virus
Functional expression and membrane fusion tropism of the envelope glycoproteins of Hendra virus
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DOI：
10.1006/viro.2001.1158
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发表时间：
2001-11-10
期刊：
影响因子：
3.7
通讯作者：
Broder, CC
中科院分区：
文献类型：
--
作者：
Bossart, KN;Wang, LF;Broder, CC
亨德拉病毒（HeV）是一种新出现的副粘病毒，首次从严重呼吸道疾病病例中分离出来，这些疾病对马和人都有致命影响。了解宿主细胞感染和跨物种传播的机制是应对这些新出现的病原体带来的风险的重要一步。我们已经开始研究表征HeV包膜糖蛋白的生物学特性。产生编码HeV F和G开放阅读框的重组牛痘病毒，并通过代谢标记和使用特异性抗血清的检测来验证糖蛋白表达。糖蛋白的功能和细胞的向性进行了检查与HeV介导的膜融合的定量测定。通过抗HeV抗血清的特异性抑制验证融合特异性，并且对应于F HeV的α-螺旋七肽重复序列之一的肽需要F和G两者来介导融合。已经鉴定了允许的靶细胞，包括来自猫、蝙蝠、马、人、猴、小鼠和兔的细胞系。还鉴定了融合阴性细胞类型。用蛋白酶处理靶细胞后，融合活性消失，这表明病毒利用细胞表面蛋白作为其受体。
Hendra virus (HeV) is an emerging paramyxovirus first isolated from cases of severe respiratory disease that fatally affected both horses and humans. Understanding the mechanisms of host cell infection and cross-species transmission is an important step in addressing the risk posed by such emerging pathogens. We have initiated studies to characterize the biological properties of the HeV envelope glycoproteins. Recombinant vaccinia viruses encoding the HeV F and G open reading frames were generated and glycoprotein expression was verified by metabolic labeling and detection using specific antisera. Glycoprotein function and cellular tropism were examined with a quantitative assay for HeV-mediated membrane fusion. Fusion specificity was verified through specific inhibition by anti-HeV antiserum and a peptide corresponding to one of the alpha -helical heptad repeats of F HeV requires both F and G to mediate fusion. Permissive target cells have been identified, including cell lines derived from cat, bat, horse, human, monkey, mouse, and rabbit. Fusion negative cell types have also been identified. Protease treatments of the target cells abolished fusion activity, suggesting that the virus is employing a cell-surface protein as its receptor.