Reversible conformational change in herpes simplex virus glycoprotein B with fusion-from-without activity is triggered by mildly acidic pH.
Reversible conformational change in herpes simplex virus glycoprotein B with fusion-from-without activity is triggered by mildly acidic pH.
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DOI：
10.1186/1743-422x-7-352
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发表时间：
2010-12-01
期刊：
影响因子：
4.8
通讯作者：
Nicola AV
中科院分区：
文献类型：
--
作者：
Siekavizza-Robles CR;Dollery SJ;Nicola AV
单纯疱疹病毒（HSV）融合蛋白gB的融合前形式在体外和病毒进入期间经历pH触发的构象变化（Dollery等人，J. Virol. 84：3759-3766，2010）。来自HSV-1 ANG路径的无融合（FFWO）毒株的gB的抗原结构类似于经历pH触发变化的野生型gB。总之，gB的抗原性和寡聚体构象的变化与融合活性相关。我们测试了FFWO gB的融合前形式是否响应于低pH而经历改变的构象变化。5.5 - 6.0的pH改变了FFWO gB的结构域I和V的构象，它们一起构成含有疏水融合环的功能区。ANG途径gB寡聚体在相似的pH值下发生改变。所有变化都是可逆的。在缺乏UL 45蛋白的野生型HSV中，其与gB介导的融合有关，gB仍然经历pH触发的变化。ANG路径条目被灭活预处理的病毒粒子与低pH值。融合活性增强的gB融合前的构象发生改变的抗原结构和寡聚体的构象在响应酸性pH值。我们建议，内体pH值触发构象变化的突变gB与FFWO活性的方式类似于野生型。除了该触发之外的差异可以解释FFWO gB的融合活性增加。
The pre-fusion form of the herpes simplex virus (HSV) fusion protein gB undergoes pH-triggered conformational change in vitro and during viral entry (Dollery et al., J. Virol. 84:3759-3766, 2010). The antigenic structure of gB from the fusion-from-without (FFWO) strain of HSV-1, ANG path, resembles wild type gB that has undergone pH-triggered changes. Together, changes in the antigenic and oligomeric conformation of gB correlate with fusion activity. We tested whether the pre-fusion form of FFWO gB undergoes altered conformational change in response to low pH. A pH of 5.5 - 6.0 altered the conformation of Domains I and V of FFWO gB, which together comprise the functional region containing the hydrophobic fusion loops. The ANG path gB oligomer was altered at a similar pH. All changes were reversible. In wild type HSV lacking the UL45 protein, which has been implicated in gB-mediated fusion, gB still underwent pH-triggered changes. ANG path entry was inactivated by pretreatment of virions with low pH. The pre-fusion conformation of gB with enhanced fusion activity undergoes alteration in antigenic structure and oligomeric conformation in response to acidic pH. We propose that endosomal pH triggers conformational change in mutant gB with FFWO activity in a manner similar to wild type. Differences apart from this trigger may account for the increased fusion activity of FFWO gB.