University of Duisburg-Essen, University Hospital Essen, Institute for Translational HIV Research; Essen, Germany.
Ragon Institute of MGH, MIT and Harvard; Cambridge, Massachusetts, United States of America.
PLoS Pathog. 2022 Sep 6;18(9):e1010738. doi: 10.1371/journal.ppat.1010738. eCollection 2022 Sep.
While Epstein-Barr virus causes mostly asymptomatic infection, associated malignancies, and autoimmune and lymphoproliferative diseases occur. To dissect the evolution of humoral immune responses over the course of EBV infection and to gain a better understanding of the potential contribution of antibody (Ab) function to viral control, we comprehensively profiled Ab specificities and Fc-functionalities using systems serology and VirScan. Ab functions against latent (EBNA1), early (p47/54) and two late (gp350/220 and VCA-p18) EBV proteins were overall modest and/or short-lived, differing from humoral responses induced during acute infection by other viruses such as HIV. In the first year post infection, only p18 elicited robust IgM-driven complement deposition and IgG-driven neutrophil phagocytosis while responses against EBNA-1 were largely Fc-functionally silent and only matured during chronic infection to drive phagocytosis. In contrast, Abs against Influenza virus readily mediated broad Fc-activity in all participants. These data suggest that EBV evades the induction of robust Fc-functional Abs, potentially due to the virus' life cycle, switching from lytic to latent stages during infection.
虽然 Epstein-Barr 病毒主要引起无症状感染，但与之相关的恶性肿瘤、自身免疫和淋巴增生性疾病也会发生。为了剖析 EBV 感染过程中体液免疫反应的演变，并更好地了解抗体（Ab）功能对病毒控制的潜在贡献，我们使用系统血清学和 VirScan 全面分析了 Ab 的特异性和 Fc 功能。针对潜伏（EBNA1）、早期（p47/54）和两个晚期（gp350/220 和 VCA-p18）EBV 蛋白的 Ab 功能总体上较为温和和/或短暂，与 HIV 等其他病毒引起的急性感染时诱导的体液免疫反应不同。在感染后第一年，只有 p18 引发了强烈的 IgM 驱动的补体沉积和 IgG 驱动的中性粒细胞吞噬作用，而针对 EBNA-1 的反应在很大程度上是 Fc 功能沉默的，仅在慢性感染期间成熟以驱动吞噬作用。相比之下，流感病毒的抗体容易在所有参与者中介导广泛的 Fc 活性。这些数据表明，EBV 逃避了诱导强烈的 Fc 功能 Ab 的产生，这可能是由于病毒的生命周期，在感染过程中从裂解阶段转变为潜伏阶段。
