Clinical Neurology Research Group, Division of Clinical Neuroscience, University of Nottingham School of Medicine, Nottingham, United Kingdom.
Centre de Physiopathologie de Toulouse Purpan, UPS, INSERM, CNRS Université de Toulouse, Toulouse, France.
Front Immunol. 2019 Jan 22;9:3092. doi: 10.3389/fimmu.2018.03092. eCollection 2018.
The expression of human endogenous retroviruses (HERVs) has been associated with Multiple Sclerosis (MS). The MS-related retrovirus (MSRV/HERV-W) has the potential to activate inflammatory immunity, which could promote both susceptibility and progression toward MS. A connection between HERVs and MS is also supported by the observation that people infected with the human immunodeficiency virus (HIV) may have a lower risk of developing MS than the HIV non-infected, healthy population. This may be due to suppression of HERV expression by antiretroviral therapies (ART) used to treat HIV infection. In this pilot study, we compared RNA expression of the envelope gene of MSRV/HERV-W, as well as Toll-like receptors (TLR) 2 and 4, in a small cohort of HIV+ patients with MS patients and healthy controls (HC). An increased expression of MSRV/HERV-W and TLR2 RNA was detected in blood of MS patients compared with HIV patients and HC, while TLR4 was increased in both MS and HIV patients. There was, however, no difference in MSRV/HERV-W, TLR2 and TLR4 expression between ART-treated and -untreated HIV patients. The viral protein Env was expressed mainly by B cells and monocytes, but not by T cells and EBV infection could induce the expression of MSRV/HERV-W in Lymphoblastoid cell lines (LCLs). LCLs were therefore used as an system to test the efficacy of ART in inhibiting the expression of MSRV/HERV-W. Efavirenz (a non-nucleoside reverse transcriptase inhibitor) alone or different combined drugs could reduce MSRV/HERV-W expression . Further, experiments are needed to clarify the potential role of ART in protection from MS.
人类内源性逆转录病毒（HERV）的表达与多发性硬化症（MS）有关。与 MS 相关的逆转录病毒（MSRV/HERV-W）有可能激活炎症免疫，从而促进 MS 的易感性和进展。HERV 与 MS 之间的联系也得到了以下观察结果的支持：感染人类免疫缺陷病毒（HIV）的人患 MS 的风险可能低于未感染 HIV 的健康人群。这可能是由于用于治疗 HIV 感染的抗逆转录病毒疗法（ART）抑制了 HERV 的表达。在这项初步研究中，我们比较了 MSRV/HERV-W 的包膜基因以及 Toll 样受体（TLR）2 和 4 在一小部分 HIV+MS 患者、MS 患者和健康对照者（HC）中的 RNA 表达。与 HIV 患者和 HC 相比，MS 患者的血液中检测到 MSRV/HERV-W 和 TLR2 RNA 的表达增加，而 TLR4 在 MS 和 HIV 患者中均增加。然而，ART 治疗和未治疗的 HIV 患者之间 MSRV/HERV-W、TLR2 和 TLR4 的表达没有差异。病毒蛋白 Env 主要由 B 细胞和单核细胞表达，但 T 细胞不表达，EBV 感染可诱导 LCL 中 MSRV/HERV-W 的表达。因此，LCL 被用作检测 ART 抑制 MSRV/HERV-W 表达的疗效的系统。单独使用依非韦伦（一种非核苷类逆转录酶抑制剂）或不同的联合药物均可降低 MSRV/HERV-W 的表达。需要进一步的实验来阐明 ART 在预防 MS 方面的潜在作用。
