Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature.
Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature.
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丙型肝炎病毒表位暴露和抗体中和受时间和温度的影响。
DOI：
10.1016/j.virol.2011.10.023
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Diamond,MichaelS
中科院分区：
文献类型：
--
作者：
Sabo,MichelleC;Luca,VincentC;Ray,StuartC;Bukh,Jens;Fremont,DavedH;Diamond,MichaelS
最近的一项黄病毒研究表明，病毒粒子的结构动力学通过暴露表面上神秘的表位来影响抗体中和。为了确定这是否适用于远缘丙型肝炎病毒 (HCV)，其中和表位可能被聚糖屏蔽、载脂蛋白相互作用和 E2 包膜蛋白上的高变区所掩盖，我们评估了预孵育的时间和温度如何改变单克隆抗体 (MAb) 对 HCV 的中和作用。值得注意的是，当在 37°C 下进行预结合或经过较长的预孵育时间后，几种 MAb 显示出增加的抑制活性，并且当在 4°C 下进行预结合时观察到相应的中和损失。在 HCV 感染患者的急性期和慢性期血清中观察到类似的变化。我们的数据表明，孵育时间和温度调节 HCV 病毒体构象整体上的表位暴露，从而改变抗体中和的效力。
A recent study with flaviviruses suggested that structural dynamics of the virion impact antibody neutralization via exposure of ostensibly cryptic epitopes. To determine whether this holds true for the distantly related hepatitis C virus (HCV), whose neutralizing epitopes may be obscured by a glycan shield, apolipoprotein interactions, and the hypervariable region on the E2 envelope protein, we assessed how time and temperature of pre-incubation altered monoclonal antibody (MAb) neutralization of HCV. Notably, several MAbs showed increased inhibitory activity when pre-binding was performed at 37°C or after longer pre-incubation periods, and a corresponding loss-of-neutralization was observed when pre-binding was performed at 4°C. A similar profile of changes was observed with acute and chronic phase sera from HCV-infected patients. Our data suggest that time and temperature of incubation modulate epitope exposure on the conformational ensembles of HCV virions and thus, alter the potency of antibody neutralization.