Gill Michael B, Gillet Laurent, Colaco Susanna, May Janet S, de Lima Brigitte D, Stevenson Philip G
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
J Gen Virol. 2006 Jun;87(Pt 6):1465-1475. doi: 10.1099/vir.0.81760-0.
Herpesviruses characteristically persist in immune hosts as latent genomes, but to transmit infection they must reactivate and replicate lytically. The interaction between newly formed virions and pre-existing antibody is therefore likely to be a crucial determinant of viral fitness. Murine gammaherpesvirus-68 (MHV-68) behaves as a natural pathogen of conventional, inbred mice and consequently allows such interactions to be analysed experimentally in a relatively realistic setting. Here, monoclonal antibodies (mAbs) were derived from MHV-68-infected mice and all those recognizing infected-cell surfaces were tested for their capacity to neutralize MHV-68 virions. All of the neutralizing mAbs identified were specific for the viral glycoprotein H (gH)-gL heterodimer and required both gH and gL to reproduce their cognate epitopes. Based on antibody interference, there appeared to be two major neutralization epitopes on gH-gL. Analysis of a representative mAb indicated that it blocked infection at a post-binding step--either virion endocytosis or membrane fusion.
疱疹病毒通常以潜伏基因组的形式在免疫宿主中持续存在，但为了传播感染，它们必须重新激活并进行裂解复制。因此，新形成的病毒粒子与预先存在的抗体之间的相互作用很可能是病毒适应性的关键决定因素。小鼠γ-疱疹病毒68（MHV-68）是传统近交系小鼠的天然病原体，因此可以在相对现实的环境中通过实验分析这种相互作用。在这里，单克隆抗体（mAb）来源于感染MHV-68的小鼠，所有识别感染细胞表面的抗体都被测试了中和MHV-68病毒粒子的能力。鉴定出的所有中和性单克隆抗体都对病毒糖蛋白H（gH）-gL异二聚体具有特异性，并且需要gH和gL两者才能重现其同源表位。基于抗体干扰，gH-gL上似乎有两个主要的中和表位。对一种代表性单克隆抗体的分析表明，它在结合后步骤——病毒粒子内吞或膜融合——阻断感染。
