Sotelo Julio, Martínez-Palomo Adolfo, Ordoñez Graciela, Pineda Benjamin
Neuroimmunology Unit, National Institute of Neurology and Neurosurgery, Center for Research and Advanced Studies, Mexico City, Mexico.
Ann Neurol. 2008 Mar;63(3):303-11. doi: 10.1002/ana.21316.
Recent studies in peripheral blood mononuclear cells (PBMCs) have indicated that exacerbations of multiple sclerosis (MS) could be associated with the reactivation of latent varicella-zoster virus (VZV).
Ultrastructural observations for viral particles were made by electron microscopy in cerebrospinal fluid (CSF) from 15 MS patients during relapse, 19 MS patients during remission, and 28 control subjects. Initial findings were reproduced in a confirmation cohort. In addition, DNA from VZV was quantified by real-time polymerase chain reaction in PBMCs and CSF from a large number of MS patients (n = 78).
We found by electron microscopy the presence of abundant viral particles identical to VZV in CSF obtained from MS patients within the first few days of an acute relapse. In contrast, viral particles were not seen in CSF samples from MS patients in remission or from neurological control subjects. Also, DNA from VZV was present in CSF and in PBMCs during relapse, disappearing in most patients during remission. The mean viral load was 542 times greater in CSF at relapse than in CSF at remission and 328 times greater in CSF at relapse than in PBMCs at relapse.
The ultrastructural finding of viral particles identical to VZV, together with the simultaneous presence of large quantities of DNA from VZV in the subarachnoid space, almost restricted to the periods of exacerbation, as well as its steady diminution and eventual disappearance from clinical relapse to clinical remission are surprising and constitute the strongest evidence to support the participation of VZV in the pathogenesis of MS.
近期对外周血单核细胞（PBMCs）的研究表明，多发性硬化症（MS）病情加重可能与潜伏性水痘 - 带状疱疹病毒（VZV）的重新激活有关。
通过电子显微镜对15例复发期MS患者、19例缓解期MS患者和28例对照者的脑脊液（CSF）进行病毒颗粒的超微结构观察。初步研究结果在一个验证队列中得到重现。此外，通过实时聚合酶链反应对大量MS患者（n = 78）的PBMCs和CSF中的VZV DNA进行定量分析。
我们通过电子显微镜发现在急性复发的最初几天内从MS患者获得的CSF中存在大量与VZV相同的病毒颗粒。相比之下，在缓解期MS患者或神经对照者的CSF样本中未见到病毒颗粒。而且，复发期间CSF和PBMCs中存在VZV DNA，在大多数患者缓解期消失。复发时CSF中的平均病毒载量比缓解时CSF中的病毒载量高542倍，复发时CSF中的病毒载量比复发时PBMCs中的病毒载量高328倍。
与VZV相同的病毒颗粒的超微结构发现，以及蛛网膜下腔中几乎仅限于病情加重期同时存在大量VZV DNA，以及从临床复发到临床缓解其稳定减少并最终消失，这些令人惊讶，构成了支持VZV参与MS发病机制的最有力证据。
