Laboratory of Microbiology and Virology, Vita-Salute, San Raffaele University, Milan, Italy.
Laboratory of Microbiology and Virology, San Raffaele Hospital, Milan, Italy.
J Virol. 2019 May 15;93(11). doi: 10.1128/JVI.00070-19. Print 2019 Jun 1.
Herpes simplex virus 1 (HSV-1) and HSV-2 can evade serum antibody-mediated neutralization through cell-to-cell transmission mechanisms, which represent one of the central steps in disease reactivation. To address the role of humoral immunity in controlling HSV-1 and HSV-2 replication, we analyzed serum samples from 44 HSV-1 and HSV-2 seropositive subjects by evaluating (i) their efficiency in binding both the purified viral particles and recombinant gD and gB viral glycoproteins, (ii) their neutralizing activity, and (iii) their capacity to inhibit the cell-to-cell virus passage All of the sera were capable of binding gD, gB, and whole virions, and all sera significantly neutralized cell-free virus. However, neither whole sera nor purified serum IgG fraction was able to inhibit significantly cell-to-cell virus spreading in post-virus-entry infectious assays. Conversely, when spiked with an already described anti-gD human monoclonal neutralizing antibody capable of inhibiting HSV-1 and -2 cell-to-cell transmission, each serum boosted both its neutralizing and post-virus-entry inhibitory activity, with no interference exerted by serum antibody subpopulations. Despite its importance in the physiopathology of HSV-1 and -2 infections, the cell-to-cell spreading mechanism is still poorly understood. The data shown here suggest that infection-elicited neutralizing antibodies capable of inhibiting cell-to-cell virus spread can be underrepresented in most infected subjects. These observations can be of great help in better understanding the role of humoral immunity in controlling virus reactivation and in the perspective of developing novel therapeutic strategies, studying novel correlates of protection, and designing effective vaccines.
单纯疱疹病毒 1（HSV-1）和单纯疱疹病毒 2（HSV-2）可以通过细胞间传播机制逃避血清抗体介导的中和作用，这是疾病复发的关键步骤之一。为了研究体液免疫在控制 HSV-1 和 HSV-2 复制中的作用，我们通过评估（i）其结合纯化病毒颗粒和重组 gD 和 gB 病毒糖蛋白的效率，（ii）中和活性，以及（iii）抑制细胞间病毒传递的能力，分析了 44 例 HSV-1 和 HSV-2 血清阳性受试者的血清样本。所有血清均能结合 gD、gB 和整个病毒粒子，所有血清均能显著中和无细胞病毒。然而，在病毒进入后感染性测定中，整个血清或纯化的血清 IgG 级分均不能显著抑制细胞间病毒传播。相反，当用已描述的能够抑制 HSV-1 和 HSV-2 细胞间传播的抗 gD 人源单克隆中和抗体进行处理时，每种血清均能提高其中和和病毒进入后抑制活性，而血清抗体亚群没有产生干扰。尽管细胞间传播机制在 HSV-1 和 HSV-2 感染的病理生理学中很重要，但它仍未得到充分理解。这里显示的数据表明，能够抑制细胞间病毒传播的感染诱导中和抗体在大多数感染个体中可能存在代表性不足。这些观察结果对于更好地理解体液免疫在控制病毒再激活中的作用，以及在开发新的治疗策略、研究新的保护相关性和设计有效的疫苗方面具有重要意义。
