Environmental Factors in Degenerative Diseases Research Group, Instituto Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, Spain.
Neurology Department, Hospital Universitario Quirónsalud Madrid, Madrid, Spain.
Front Immunol. 2020 Sep 18;11:2142. doi: 10.3389/fimmu.2020.02142. eCollection 2020.
Human herpesvirus-6A (HHV-6A) and -6B (HHV-6B) might be involved in the etiopathogenesis of multiple sclerosis (MS), especially the HHV-6A. We aim at assessing, for the first time in the scientific literature, the HHV-6A/B microRNAs in MS patients. We analyzed the miRNAs of HHV-6A: miR-U86, and -6B: hhv6b-miR-Ro6-1, -2, -3-3p, -3-5p, and -4 in paired samples of serum and CSF of 42 untreated MS patients and 23 patients with other neurological diseases (OND), using Taqman MicroRNA Assays. Intrathecal HHV-6A/B antibody production and anti-HHV-6A/B IgG/IgM levels in serum were measured. MS clinical data were available. We detected the following miRNAs: hhv6b-miR-Ro6-2 (serum: MS:97.7%, OND:95.7%; CSF: MS:81%, OND:86.4%), 3-3p (serum: MS:4.8%, OND:0%; CSF: MS:2.4%, OND:4.5%), -3-5p (serum: MS:95.2%, OND:91.3%; CSF: MS:50%, OND:54.5%), and miR-U86 (serum: MS:54.8%, OND:47.8%; CSF: MS:11.9%, OND:9.1%). In the serum of the whole population (MS and OND patients) we found a significant correlation between the levels of hhv6b-miR-Ro6-2 and -3-5p (Spearman = 0.839, pcorr = 3E-13), -2 and miR-U86 (Spearman = 0.578, pcorr = 0.001) and -3-5p and miR-U86 (Spearman = 0.698, pcorr = 1.34E-5); also in the CSF, between hhv6b-miR-Ro6-2 and -3-5p (Spearman = 0.626, pcorr = 8.52E-4). These correlations remained statistically significant when both populations were considered separately. The anti-HHV-6A/B IgG levels in CSF and the intrathecal antibody production in positive MS patients for hhv6b-miR-Ro6-3-5p were statistically significant higher than in the negative ones (pcorr = 0.006 and pcorr = 0.036). The prevalence of miR-U86 (30.8%) in the CSF of individuals without gadolinium-enhancing lesions was higher ( = 0.035) than in the ones with these lesions (0%); however, the difference did not withstand Bonferroni correction (pcorr = 0.105). We propose a role of HHV-6A/B miRNAs in the maintenance of the viral latency state. Further investigations are warranted to validate these results and clarify the function of these viral miRNAs.
人疱疹病毒 6A（HHV-6A）和 -6B（HHV-6B）可能参与多发性硬化症（MS）的发病机制，特别是 HHV-6A。我们旨在首次在科学文献中评估 MS 患者的 HHV-6A/B 微 RNA。我们分析了 HHV-6A 的 miRNA：miR-U86 和 -6B：hhv6b-miR-Ro6-1、-2、-3-3p、-3-5p 和 -4，在 42 名未经治疗的 MS 患者和 23 名其他神经系统疾病（OND）患者的血清和 CSF 配对样本中，使用 Taqman MicroRNA 检测。测量了鞘内 HHV-6A/B 抗体产生和血清中的抗 HHV-6A/B IgG/IgM 水平。可获得 MS 临床数据。我们检测到以下 miRNA：hhv6b-miR-Ro6-2（血清：MS：97.7%，OND：95.7%；CSF：MS：81%，OND：86.4%），3-3p（血清：MS：4.8%，OND：0%；CSF：MS：2.4%，OND：4.5%），-3-5p（血清：MS：95.2%，OND：91.3%；CSF：MS：50%，OND：54.5%）和 miR-U86（血清：MS：54.8%，OND：47.8%；CSF：MS：11.9%，OND：9.1%）。在整个人群（MS 和 OND 患者）的血清中，我们发现 hhv6b-miR-Ro6-2 和 -3-5p 之间存在显著相关性（Spearman = 0.839，pcorr = 3E-13），-2 和 miR-U86（Spearman = 0.578，pcorr = 0.001）和 -3-5p 和 miR-U86（Spearman = 0.698，pcorr = 1.34E-5）；同样在 CSF 中，hhv6b-miR-Ro6-2 和 -3-5p 之间也存在相关性（Spearman = 0.626，pcorr = 8.52E-4）。当分别考虑两个群体时，这些相关性仍然具有统计学意义。CSF 中的抗 HHV-6A/B IgG 水平和 hhv6b-miR-Ro6-3-5p 阳性 MS 患者的鞘内抗体产生均明显高于阴性患者（pcorr = 0.006 和 pcorr = 0.036）。无钆增强病变个体 CSF 中 miR-U86（30.8%）的发生率（ = 0.035）高于有这些病变的个体（0%）；然而，这种差异在经过 Bonferroni 校正后并不显著（pcorr = 0.105）。我们提出 HHV-6A/B 微 RNA 在维持病毒潜伏状态中的作用。需要进一步研究来验证这些结果并阐明这些病毒微 RNA 的功能。
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