Asymptomatic Primary Infection with Epstein-Barr Virus: Observations on Young Adult Cases.
Asymptomatic Primary Infection with Epstein-Barr Virus: Observations on Young Adult Cases.
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DOI：
10.1128/jvi.00382-17
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发表时间：
2017-11-01
影响因子：
5.4
通讯作者：
Bell AI
中科院分区：
文献类型：
--
作者：
Abbott RJ;Pachnio A;Pedroza-Pacheco I;Leese AM;Begum J;Long HM;Croom-Carter D;Stacey A;Moss PAH;Hislop AD;Borrow P;Rickinson AB;Bell AI
EB病毒（EBV）通常在儿童时期无症状地获得。相反，在生命后期感染通常导致传染性单核细胞增多症（IM），这是一种发热性疾病，其特征为抗EBV IgM抗体阳性，高负荷的循环潜伏感染B细胞，以及由EBV特异性CD8+ T细胞过度扩增加上CD56 dim NKG2A+ KIR−自然杀伤（NK）细胞轻度扩增引起的显著淋巴细胞增多症。由于缺乏对临床无症状感染的研究，这两种情况如何比较尚不清楚。在这里，我们描述了五个前瞻性研究的无症状感染的大学新生的血清流行病学调查确定的患者。在每种情况下，关键血液样本具有高细胞相关病毒载量，而没有明显的CD8淋巴细胞增多或NK细胞紊乱，如IM急性期患者中所见。其中两例病毒载量最高的病例显示活化的EBV特异性CD8+ T细胞同时扩增，但总体CD8+ T细胞数量未受影响或仅轻度增加。两例载量稍低的病例，血清学表明感染可能在感染过程中较早被发现，当时也没有显示T或NK细胞扩增。有趣的是，在另一个病毒载量较高的病例中，在检测到感染的原始血液样本中检测不到T和NK细胞反应，EBV特异性T细胞反应直到几个月后才出现，此时血液中的病毒载量已经下降。因此，一些无症状原发性感染患者的循环病毒载量非常高，与IM急性期患者相似，细胞介导的免疫应答在性质上与IM患者相似，但幅度较低。然而，其他患者可能有完全不同的免疫反应，最终可能揭示宿主控制的新机制。重要性EB病毒（EBV）经口传播，在咽喉中复制，然后通过生长转化潜伏感染侵入B淋巴细胞池。虽然儿童期的原发性感染通常无症状，但迟发性感染与传染性单核细胞增多症（IM）有关，这是一种发热性疾病，患者具有高循环病毒载量和夸大的病毒诱导的免疫应答，涉及CD8+ T细胞和自然杀伤（NK）细胞。在这里，我们表明，在5例无症状感染，血液中的病毒载量是一样高的那些在急性期的IM患者，而细胞介导的反应，即使他们类似于那些在急性期的IM患者的时间和质量，从来没有夸大。我们推断IM症状的出现不是病毒感染本身的结果，而是过度激活的免疫反应。有趣的是，在无症状病例中，病毒载量和反应动力学之间的关系存在特异性差异，这强调了对原发性EBV感染仍有多少需要了解。
Epstein-Barr virus (EBV) is typically acquired asymptomatically in childhood. In contrast, infection later in life often leads to infectious mononucleosis (IM), a febrile illness characterized by anti-EBV IgM antibody positivity, high loads of circulating latently infected B cells, and a marked lymphocytosis caused by hyperexpansion of EBV-specific CD8+ T cells plus a milder expansion of CD56dim NKG2A+ KIR− natural killer (NK) cells. How the two situations compare is unclear due to the paucity of studies on clinically silent infection. Here we describe five prospectively studied patients with asymptomatic infections identified in a seroepidemiologic survey of university entrants. In each case, the key blood sample had high cell-associated viral loads without a marked CD8 lymphocytosis or NK cell disturbance like those seen in patients during the acute phase of IM. Two of the cases with the highest viral loads showed a coincident expansion of activated EBV-specific CD8+ T cells, but overall CD8+ T cell numbers were either unaffected or only mildly increased. Two cases with slightly lower loads, in whom serology suggests the infection may have been caught earlier in the course of infection, also showed no T or NK cell expansion at the time. Interestingly, in another case with a higher viral load, in which T and NK cell responses were undetectable in the primary blood sample in which infection was detected, EBV-specific T cell responses did not appear until several months later, by which time the viral loads in the blood had already fallen. Thus, some patients with asymptomatic primary infections have very high circulating viral loads similar to those in patients during the acute phase of IM and a cell-mediated immune response that is qualitatively similar to that in IM patients but of a lower magnitude. However, other patients may have quite different immune responses that ultimately could reveal novel mechanisms of host control. IMPORTANCE Epstein-Barr virus (EBV) is transmitted orally, replicates in the throat, and then invades the B lymphocyte pool through a growth-transforming latent infection. While primary infection in childhood is usually asymptomatic, delayed infection is associated with infectious mononucleosis (IM), a febrile illness in which patients have high circulating viral loads and an exaggerated virus-induced immune response involving both CD8+ T cells and natural killer (NK) cells. Here we show that in five cases of asymptomatic infection, viral loads in the blood were as high as those in patients during the acute phase of IM, whereas the cell-mediated responses, even when they resembled those in patients during the acute phase of IM in timing and quality, were never as exaggerated. We infer that IM symptoms arise as a consequence not of the virus infection per se but of the hyperactivated immune response. Interestingly, there were idiosyncratic differences among asymptomatic cases in the relationship between the viral load and the response kinetics, emphasizing how much there is still to learn about primary EBV infection.