The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparan sulfate
The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparan sulfate
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DOI：
10.1128/jvi.74.14.6442-6447.2000
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发表时间：
2000-07-01
影响因子：
5.4
通讯作者：
Beeler, JA
中科院分区：
文献类型：
--
作者：
Feldman, SA;Audet, S;Beeler, JA
人呼吸道合胞病毒 (RSV) F 糖蛋白 (RSV-F) 可以独立地与固定化肝素相互作用，并通过与细胞硫酸乙酰肝素相互作用促进细胞的附着和感染。使用肝素琼脂糖亲和层析评估 RSV-糖胺聚糖 (GAG) 相互作用。来自 A2 和 B1/cp-52 (cp-52) 感染细胞裂解物的 RSV-F、源自重组牛痘病毒的 RSV F 以及亲和纯化的 F 蛋白均与肝素柱结合并被特异性洗脱。在感染性抑制研究中，可溶性 GAG 降低了 RSV A2 和 cp-52 的感染性，牛肺肝素对 A2（50% 有效剂量 [ED50] = 0.28 +/- 0.11 mu g/ml）和 cp-52（ED50 = 0.55 +/- 0.14 mu g/ml）表现出最高的比活性。此外，肝素裂解酶 I 和肝素裂解酶 III（而非软骨素酶 ABC）对细胞表面 GAG 的酶消化导致 cp-52 感染性显着降低。此外，牛肺肝素可抑制放射性标记的 A2 和 cp-52 病毒结合高达 30%。总而言之，这些数据表明 RSV-F 独立地与肝素/硫酸乙酰肝素相互作用，并且这种类型的相互作用促进病毒附着和感染性。
Human respiratory syncytial virus (RSV) F glycoprotein (RSV-F) can independently interact with immobilized heparin and facilitate both attachment to and infection of cells via an interaction with cellular heparan sulfate. RSV-glycosaminoglycan (GAG) interactions were evaluated using heparin agarose affinity chromatography. RSV-F from A2- and B1/cp-52 (cp-52)-infected cell lysates, RSV F derived from a recombinant vaccinia virus, and affinity-purified F protein all bound to and were specifically eluted from heparin columns. In infectivity inhibition studies, soluble GAGs decreased the infectivity of RSV A2 and cp-52, with bovine lung heparin exhibiting the highest specific activity against both A2 (50% effective dose [ED50] = 0.28 +/- 0.11 mu g/ml) and cp-52 (ED50 = 0.55 +/- 0.14 mu g/ml). Furthermore, enzymatic digestion of cell surface GAGs by heparin lyase I and heparin lyase III but not chondroitinase ABC resulted in a significant reduction in cp-52 infectivity. Moreover, bovine lung heparin inhibited radiolabeled A2 and cp-52 virus binding up to 30%. Taken together, these data suggest that RSV-F independently interacts with heparin/heparan sulfate and this type of interaction facilitates virus attachment and infectivity.