Glycoprotein G isoforms from some alpha herpesviruses function as broad-spectrum chemokine binding proteins
Glycoprotein G isoforms from some alpha herpesviruses function as broad-spectrum chemokine binding proteins
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DOI：
10.1093/emboj/cdg092
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发表时间：
2003-02-17
期刊：
影响因子：
11.4
通讯作者：
Alcami, A
中科院分区：
文献类型：
--
作者：
Bryant, NA;Davis-Poynter, N;Alcami, A
模拟宿主趋化因子和趋化因子受体以调节趋化因子活性是β-和γ-疱疹病毒编码的策略，但关于α-疱疹病毒编码的抗趋化因子策略的信息非常有限。迄今为止，趋化因子结合蛋白（vCKBP）的分泌被认为是痘病毒和γ疱疹病毒编码的独特策略。我们描述了马疱疹病毒1型、牛疱疹病毒1型和5型以及相关的α疱疹病毒中的一个新的vCKBP家族，它们与趋化因子受体或其他vCKBP没有序列相似性。我们表明，糖蛋白G（gG）是从感染的细胞分泌，结合广泛的趋化因子具有高亲和力，并阻止其与特定受体的相互作用，阻止趋化因子的活性。此外，gG还阻断趋化因子与糖胺聚糖的结合，这是趋化因子在体内正确呈递和功能所需的相互作用。与其他vCKBP相反，gG也可以是膜锚定的，并且我们始终在表达全长蛋白的细胞表面显示趋化因子结合活性。这些α疱疹病毒vCKBP代表了一个新的蛋白质家族，在膜和溶液中结合趋化因子。
Mimicry of host chemokines and chemokine receptors to modulate chemokine activity is a strategy encoded by beta- and gammaherpesviruses, but very limited information is available on the anti-chemokine strategies encoded by alphaherpesviruses. The secretion of chemokine binding proteins (vCKBPs) has hitherto been considered a unique strategy encoded by poxviruses and gammaherpesviruses. We describe a family of novel vCKBPs in equine herpesvirus 1, bovine herpesvirus 1 and 5, and related alphaherpesviruses with no sequence similarity to chemokine receptors or other vCKBPs. We show that glycoprotein G (gG) is secreted from infected cells, binds a broad range of chemokines with high affinity and blocks chemokine activity by preventing their interaction with specific receptors. Moreover, gG also blocks chemokine binding to glycosaminoglycans, an interaction required for the correct presentation and function of chemokines in vivo. In contrast to other vCKBPs, gG may also be membrane anchored and, consistently, we show chemokine binding activity at the surface of cells expressing full-length protein. These alphaherpesvirus vCKBPs represent a novel family of proteins that bind chemokines both at the membrane and in solution.