Antibody evasion by a gammaherpesvirus O-glycan shield.
Antibody evasion by a gammaherpesvirus O-glycan shield.
复制标题
通过γ掌病毒O-Glycan盾牌逃避抗体。
DOI：
10.1371/journal.ppat.1002387
复制
发表时间：
2011-11
期刊：
影响因子：
6.7
通讯作者：
Gillet L
中科院分区：
文献类型：
--
作者：
Machiels B;Lété C;Guillaume A;Mast J;Stevenson PG;Vanderplasschen A;Gillet L
所有的伽马疱疹病毒都编码一种与Epstein-Barr病毒gp350同源的主要糖蛋白。这些糖蛋白经常参与细胞结合，有些还提供中和靶点。然而，伽马疱疹病毒从免疫宿主长期传播的能力意味着体内中和是不完整的。在这项研究中，我们使用牛疱疹病毒4(BoHV-4)来确定其gp350同源物-gp180-如何促进病毒复制和中和。缺乏gp180对BoHV-4潜伏期的建立和维持没有影响，但显著地使病毒粒子对免疫血清的中和敏感。抗体对gp180缺陷病毒粒子上的Gb、Gh和Gl有更大的亲和力，包括中和表位。Gp180似乎是高度O-糖基化的，从病毒粒子中去除O-连接的多糖也使它们对中和敏感。因此，gp180似乎为原本脆弱的病毒表位提供了部分糖链保护膜。有趣的是，这种O-葡聚糖保护层可以被凝集素和碳水化合物特异性抗体中和。所有gp350同源物中O-糖基化位点的保守表明，这是一种普遍的逃避机制，也可能提供治疗靶点。疱疹病毒在免疫宿主之间的传播意味着某种抗体的逃避。然而，其潜在的分子机制在很大程度上仍不清楚。所有的伽马疱疹病毒都编码一种与EB病毒gp350同源的主要糖蛋白。Gp350结合EB病毒与B细胞，并提供中和靶点。然而，尽管EBV携带者具有免疫原性，但它仍然具有传染性。在这里，我们展示了相关的牛疱疹病毒4(BoHV-4)的gp350同源物，gp180及其O-糖链，屏蔽了一些原本脆弱的病毒表位。广泛的O-糖基化对所有的伽马疱疹病毒gp350同源物都是共同的，这表明这种逃避机制也很普遍。
All gammaherpesviruses encode a major glycoprotein homologous to the Epstein-Barr virus gp350. These glycoproteins are often involved in cell binding, and some provide neutralization targets. However, the capacity of gammaherpesviruses for long-term transmission from immune hosts implies that in vivo neutralization is incomplete. In this study, we used Bovine Herpesvirus 4 (BoHV-4) to determine how its gp350 homolog - gp180 - contributes to virus replication and neutralization. A lack of gp180 had no impact on the establishment and maintenance of BoHV-4 latency, but markedly sensitized virions to neutralization by immune sera. Antibody had greater access to gB, gH and gL on gp180-deficient virions, including neutralization epitopes. Gp180 appears to be highly O-glycosylated, and removing O-linked glycans from virions also sensitized them to neutralization. It therefore appeared that gp180 provides part of a glycan shield for otherwise vulnerable viral epitopes. Interestingly, this O-glycan shield could be exploited for neutralization by lectins and carbohydrate-specific antibody. The conservation of O-glycosylation sites in all gp350 homologs suggests that this is a general evasion mechanism that may also provide a therapeutic target. Herpesvirus transmission between immune hosts implies some kind of antibody evasion. However, the underlying molecular mechanisms remain largely unknown. All gammaherpesviruses encode a major glycoprotein homologous to the Epstein-Barr virus (EBV) gp350. Gp350 binds EBV to B cells and provides a neutralization target. However, despite its immunogenicity, EBV carriers remain infectious. Here we show that the gp350 homolog of the related Bovine Herpesvirus 4 (BoHV-4), gp180, and its O-glycans, shield some otherwise vulnerable viral epitopes. Extensive O-glycosylation is common to all gammaherpesvirus gp350 homologs, suggesting that this evasion mechanism is also widespread.
登录
查看更多内容
DOI：
10.1073/pnas.1002717107
发表时间：
2010-10-05
影响因子：
11.1
作者：
Doores, Katie J.;Fulton, Zara;Davis, Benjamin G.
通讯作者：
Davis, Benjamin G.
DOI：
10.1073/pnas.84.5.1369
发表时间：
1987-03-01
影响因子：
11.1
作者：
GALILI, U;CLARK, MR;MACHER, BA
通讯作者：
MACHER, BA
影响因子：
3.8
作者：
DUBUISSON, J;GUILLAUME, J;PASTORET, PP
通讯作者：
PASTORET, PP
影响因子：
3.7
作者：
Dewals, Benjamin;Boudry, Christel;Vanderplasschen, Alain
通讯作者：
Vanderplasschen, Alain
影响因子：
3.8
作者：
Gillet, L;Daix, V;Vanderplasschen, A
通讯作者：
Vanderplasschen, A