The murid herpesvirus-4 gH/gL binds to glycosaminoglycans.
The murid herpesvirus-4 gH/gL binds to glycosaminoglycans.
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Murid疱疹病毒-4 GH/GL与糖胺聚糖结合。
DOI：
10.1371/journal.pone.0001669
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发表时间：
2008-02-27
期刊：
影响因子：
3.7
通讯作者：
Stevenson, Philip G.
中科院分区：
文献类型：
--
作者：
Gillet, Laurent;Colaco, Susanna;Stevenson, Philip G.
病毒与细胞的第一次接触是决定其嗜性的重要因素。小鼠疱疹病毒-4（MuHV-4）高度依赖于糖胺聚糖（GAG）与细胞结合。因此，它的第一次接触可能涉及GAG结合病毒体糖蛋白。我们之前已经鉴定了两种这样的蛋白质，gp 70和gp 150。Gp 70与GAG强烈结合。然而，删除它对MuHV-4细胞结合或GAG依赖性几乎没有影响。相比之下，删除gp 150使MuHV-4免于GAG依赖。这意味着GAG通常置换gp 150以允许GAG非依赖性细胞结合。但gp 150 GAG相互作用很弱，因此似乎不太可能进行有效的首次接触。由于gp 70和gp 150都不符合第一接触糖蛋白的预期特征，因此我们对MuHV-4 GAG相互作用的理解一定是不完整的。在这里，我们通过显示MuHV-4 gH/gL也与GAG结合来关联看似断开的gp 70和gp 150 GAG相互作用。gH/gL阻断抗体和gp 70阻断抗体单独对细胞结合几乎没有影响，但一起具有强烈的抑制作用。因此，gp 70和gH/gL之间的GAG结合存在冗余。Gp 150缺陷型MuHV-4在很大程度上抵抗gp 70和gH/gL结合的阻断，这与其GAG独立性一致。野生型MuHV-4未能做到这一点，这表明gp 150通常仅在gp 70或gH/gL的下游参与。因此，MuHV-4 GAG依赖性是双重的：gp 70或gH/gL结合为病毒体提供了重要的第一立足点，然后gp 150参与揭示GAG非依赖性结合。
The first contact a virus makes with cells is an important determinant of its tropism. Murid Herpesvirus-4 (MuHV-4) is highly dependent on glycosaminoglycans (GAGs) for cell binding. Its first contact is therefore likely to involve a GAG-binding virion glycoprotein. We have previously identified two such proteins, gp70 and gp150. Gp70 binds strongly to GAGs. However, deleting it makes little difference to MuHV-4 cell binding or GAG-dependence. Deleting gp150, by contrast, frees MuHV-4 from GAG dependence. This implies that GAGs normally displace gp150 to allow GAG-independent cell binding. But the gp150 GAG interaction is weak, and so would seem unlikely to make an effective first contact. Since neither gp70 nor gp150 matches the expected profile of a first contact glycoprotein, our understanding of MuHV-4 GAG interactions must be incomplete. Here we relate the seemingly disconnected gp70 and gp150 GAG interactions by showing that the MuHV-4 gH/gL also binds to GAGs. gH/gL-blocking and gp70-blocking antibodies individually had little effect on cell binding, but together were strongly inhibitory. Thus, there was redundancy in GAG binding between gp70 and gH/gL. Gp150-deficient MuHV-4 largely resisted blocks to gp70 and gH/gL binding, consistent with its GAG independence. The failure of wild-type MuHV-4 to do the same argues that gp150 is normally engaged only down-stream of gp70 or gH/gL. MuHV-4 GAG dependence is consequently two-fold: gp70 or gH/gL binding provides virions with a vital first foothold, and gp150 is then engaged to reveal GAG-independent binding.
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影响因子：
5.4
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