Pérez-Pérez Silvia, Domínguez-Mozo María Inmaculada, García-Martínez María Ángel, Ballester-González Rubén, Nieto-Gañán Israel, Arroyo Rafael, Alvarez-Lafuente Roberto
Environmental Factors in Degenerative Diseases Research Group, Hospital Clínico San Carlos, IdISSC, 28040 Madrid, Spain.
Immunology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.
Biomedicines. 2022 Feb 5;10(2):387. doi: 10.3390/biomedicines10020387.
pHERV-W ENV and syncytin-1, the envelope proteins of the human endogenous retrovirus W family (HERV-W), have been proposed as etiological factors for MS development. In addition, herpesviruses, such as the Epstein-Barr virus (EBV) and the human herpesvirus 6A/B (HHV-6A/B), have been also strongly associated with the disease. This work aims to study the possible link between viral loads and antibody titers against EBV and HHV-6A/B and the pHERV-W ENV/syncytin-1 protein/gene expression. For this purpose, we conducted a 12-month longitudinal study involving 98 RRMS patients. Peripheral blood samples were obtained from each patient. Serum antibody titers against EBV and HHV-6A/B were determined by ELISA, while viral loads were analyzed using qPCR. HLA MS-related alleles were also genotyped. pHERV-W ENV/syncytin-1 protein and gene expression levels in immune cells were assessed by flow cytometry and qPCR, respectively. We found that the 12-month variation of the pHERV-W ENV gene expression levels positively correlated with the variation of the EBV viral load, especially in those patients with high baseline EBV loads. Therefore, these results could support previous studies pointing to the transactivation of pHERV-W ENV by EBV. However, further studies are needed to better understand this possible relationship.
人内源性逆转录病毒W家族（HERV-W）的包膜蛋白pHERV-W ENV和合体素-1已被提出是多发性硬化症（MS）发病的病因。此外，疱疹病毒，如爱泼斯坦-巴尔病毒（EBV）和人类疱疹病毒6A/B（HHV-6A/B），也与该疾病密切相关。这项研究旨在探讨EBV和HHV-6A/B的病毒载量及抗体滴度与pHERV-W ENV/合体素-1蛋白/基因表达之间的潜在联系。为此，我们对98例复发缓解型多发性硬化症（RRMS）患者进行了为期12个月的纵向研究。采集每位患者的外周血样本。通过酶联免疫吸附测定（ELISA）法检测血清中针对EBV和HHV-6A/B的抗体滴度，同时运用定量聚合酶链反应（qPCR）分析病毒载量。还对与MS相关的人类白细胞抗原（HLA）等位基因进行基因分型。分别通过流式细胞术和qPCR评估免疫细胞中pHERV-W ENV/合体素-1蛋白和基因的表达水平。我们发现，pHERV-W ENV基因表达水平的12个月变化与EBV病毒载量的变化呈正相关，尤其是在基线EBV载量较高的患者中。因此，这些结果可能支持之前关于EBV反式激活pHERV-W ENV的研究。然而，需要进一步研究以更好地理解这种潜在关系。
