Heparin increases the infectivity of Human Papillomavirus type 16 independent of cell surface proteoglycans and induces L1 epitope exposure.
Heparin increases the infectivity of Human Papillomavirus type 16 independent of cell surface proteoglycans and induces L1 epitope exposure.
复制标题
肝素增加了独立于细胞表面蛋白聚糖的16型人乳头瘤病毒的感染性，并诱导L1表位暴露。
DOI：
10.1111/cmi.12150
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发表时间：
2013-11
影响因子：
3.4
通讯作者：
Schelhaas M
中科院分区：
文献类型：
--
作者：
Cerqueira C;Liu Y;Kühling L;Chai W;Hafezi W;van Kuppevelt TH;Kühn JE;Feizi T;Schelhaas M
人乳头瘤病毒(HPV)是宫颈癌的病原体，其中HPV-16是最常见的类型。一些HPV需要硫酸乙酰肝素蛋白多糖(HSPG)来与细胞结合。在这里，我们分析了HPV-16与增加肝素浓度的预孵育导致部分恢复而不是更有效地抑制感染的现象。在证实HSPG是HPV-16的细胞结合受体的同时，肝素预培养的病毒通过层粘连蛋白-332与细胞外基质(ECM)结合。此外，病毒粒子与肝素的相互作用允许HPV-16在没有细胞表面HSPG的情况下感染HPV-16。肝素是HSPG中硫酸乙酰肝素(HS)链高度硫酸化的代表。因此，我们得出的结论是，感染需要特定的多糖部分，而不是特定的HSPG蛋白骨架。在肝素结合后，表位特异性抗体与病毒衣壳的结合增加，这表明HPV-16病毒粒子在感染过程中通过与细胞内HSPG的类肝素结构域相互作用而发生初始构象变化。我们认为具有特定硫化模式的HS序列是促进HPV-16感染所必需的。
Human Papillomaviruses (HPVs) are the etiological agents of cervical cancer, and HPV-16 is the most prevalent type. Several HPVs require heparan sulfate proteoglycans (HSPGs) for cell-binding. Here, we analyze the phenomenon that preincubation of HPV-16 with increasing concentrations of heparin results in partial restoration rather than more efficient inhibition of infection. While corroborating that the HSPGs are cell-binding receptors for HPV-16, heparin-preincubated virus bound to the extracellular matrix (ECM) via laminin-332. Furthermore, the interaction of virions with heparin, a representative of the highly sulfated S-domains of heparan sulfate (HS) chains of HSPGs, allowed HPV-16 infection in the absence of cell surface HSPGs. Therefore, we concluded that specific glycan moieties but not specific HSPG protein backbones are required for infection. The increased binding of an epitope-specific antibody to the viral capsid after heparin-binding suggested that initial conformational changes in the HPV-16 virion occur during infection by interaction with ‘heparin-like’ domains of cellular HSPGs. We propose that HS sequences with specific sulfation patterns are required to facilitate HPV-16 infection.