Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Acta Neurol Scand. 2017 Nov;136 Suppl 201:18-21. doi: 10.1111/ane.12836.
Several lines of investigation have provided strong indications for an association between the immune-mediated, neurologic disease multiple sclerosis (MS) and human endogenous retroviruses (HERVs). Whether the relationship is causal is yet to be established. Endogenous retroviruses are pathogenic-in other species than the human. Several aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been documented, both for cells in the periphery and in the central nervous system. Specific HERV-encoded genes and certain gene products (envelope proteins, Envs) appear strongly associated with the disease and have pathogenic potential. Most HERV sequences are non-functional, whereas some HERV loci have coding potential but remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, de-repression, and also involvement of retroviral restriction factors, is emerging. Disease intervention by means of antiretrovirals has potential as a novel therapeutic strategy in MS treatment; this is compounded by the apparently reduced risk of MS in HIV infection as a consequence of therapy. Extensive studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are needed.
有几条研究线索强烈表明，免疫介导的神经系统疾病多发性硬化症（MS）与人类内源性逆转录病毒（HERV）之间存在关联。这种关系是否具有因果关系尚待确定。内源性逆转录病毒在人类以外的其他物种中是致病的。已经记录了特定 HERV 家族（HERV-H/F 和 HERV-W/MSRV）的激活和参与的几个方面，包括外周细胞和中枢神经系统中的细胞。特定的 HERV 编码基因和某些基因产物（包膜蛋白，Env）似乎与疾病强烈相关，并具有潜在的致病性。大多数 HERV 序列是非功能性的，而一些 HERV 基因座具有编码潜力，但在非病理条件下保持静止，因此涉及调节 HERV 激活、去抑制以及逆转录病毒限制因子参与的调节途径和表观遗传学的重要性正在显现。通过抗逆转录病毒进行疾病干预有可能成为 MS 治疗的一种新的治疗策略；由于治疗，HIV 感染中 MS 的风险明显降低，这使情况更加复杂。需要对 HERV 进行广泛研究，了解它们在神经疾病中的作用以及作为治疗靶点的潜力。
