Molecular parameters for precise diagnosis of asymptomatic Epstein-Barr virus reactivation in healthy carriers
Molecular parameters for precise diagnosis of asymptomatic Epstein-Barr virus reactivation in healthy carriers
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DOI：
10.1128/jcm.41.12.5419-5428.2003
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发表时间：
2003-12-01
影响因子：
9.4
通讯作者：
Jabs, WJ
中科院分区：
文献类型：
--
作者：
Maurmann, S;Fricke, L;Jabs, WJ
无症状的 Epstein-Barr 病毒 (EBV) 重新激活定期发生在口腔粘膜相关淋巴组织中。到目前为止，EBV 重新激活是通过表明病毒复制的血清学特征来诊断的。然而，血清学反应是延迟的，并不一定表明复制活动正在进行。本研究的目的是建立健康携带者参数，用于重新激活 EBV 感染的分子诊断。最近的研究强调了外周 B 细胞病毒载量的增加与远程站点的复制活动之间的关联。因此，我们使用实时 PCR 对 15 个月内 22 名健康 EBV 血清阳性献血者的外周血单核细胞 (PBMC)（病毒载量）和血浆样本（病毒血症）中的 EBV 基因组进行了定量。此外，在所有志愿者的 PBMC 中研究了编码 BZLF1 的即早期基因的转录。血清学检测显示九名捐赠者出现了重新激活，其中除了一名捐赠者外，其他所有捐赠者都至少出现过一次病毒载量显着增加。另外五人也表现出病毒载量的显着变化，但没有血清学反应。在病毒载量显着增加的 13 名志愿者中，有 6 人经历过伴随病毒载量上升的病毒血症期。在八名成人中观察到稳定的病毒载量，没有病毒血症和阴性血清学。 BZLF1 mRNA 始终检测不到。我们的结论是，对于健康受试者，血清学低估了无症状 EBV 再激活的频率。外周病毒载量和病毒血症的前瞻性检查适用于 EBV 再激活的准确诊断，这对于 EBV 再激活相当有害的免疫功能低下患者可能是有利的。
Asymptomatic Epstein-Barr virus (EBV) reactivations periodically occur in oral mucosa-associated lymphoid tissues. Until now, EBV reactivation has been diagnosed by serologic profiles that suggest virus replication. Serologic responses, however, are delayed and do not necessarily indicate ongoing replicative activity. The aim of the present study was to establish in healthy carriers parameters for a molecular diagnosis of reactivated EBV infection. Recent studies emphasized the association of an increase in peripheral-B-cell viral load with replicative activity at remote sites. Therefore, real-time PCR was used to quantitate EBV genomes in the peripheral blood mononuclear cells (PBMC) (viral load) and plasma samples (viremia) of 22 healthy EBV-seropositive blood donors over a period of 15 months. Furthermore, transcription of the immediate-early gene encoding BZLF1 was investigated in the PBMC of all volunteers. Serology suggested reactivation in nine donors, of whom all but one showed at least once a significant increase in viral load. Another five individuals also exhibited significant changes in viral load but no serologic response. Of the 13 volunteers with significant increases in viral load, 6 had a period of viremia accompanying the rise in viral load. A stable viral load without viremia and negative serology was seen in eight adults. BZLF1 mRNA was undetectable throughout. We conclude that for healthy subjects serology underestimates the frequency of asymptomatic EBV reactivations. Prospective examination of peripheral viral load and viremia is suitable for the exact diagnosis of EBV reactivation, which might be of advantage for immunocompromised patients in whom EBV reactivations are considerably harmful.