Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy.
Int J Mol Sci. 2019 Jul 29;20(15):3706. doi: 10.3390/ijms20153706.
Human endogenous retroviruses (HERVs) are genetic parasites, in-between genetics and environment. Few HERVs retain some coding capability. Sometimes, the host has the advantage of some HERV genes; conversely, HERVs may contribute to pathogenesis. The expression of HERVs depends on several factors, and is regulated epigenetically by stimuli such as inflammation, viral and microbial infections, etc. Increased expression of HERVs occurs in physiological and pathological conditions, in one or more body sites. Several diseases have been attributed to one or more HERVs, particularly neurological diseases. The key problem is to differentiate the expression of a HERV as cause or effect of a disease. To be used as a biomarker, a correlation between the expression of a certain HERV and the disease onset and/or behavior must be found. The greater challenge is to establish a pathogenic role. The criteria defining causal connections between HERVs and diseases include the development of animal models, and disease modulation in humans, by anti-HERV therapeutic antibody. So far, statistically significant correlations between HERVs and diseases have been achieved for HERV-W and multiple sclerosis; disease reproduction in transgenic animals was achieved for HERV-W and multiple sclerosis, and for HERV-K and amyotrophic lateral sclerosis. Clinical trials for both diseases are in progress.
人类内源性逆转录病毒（HERV）是介于遗传和环境之间的遗传寄生虫。少数 HERV 保留了一些编码能力。有时，宿主具有某些 HERV 基因的优势；相反，HERV 可能有助于发病机制。HERV 的表达取决于几个因素，并通过炎症、病毒和微生物感染等刺激在表观遗传上受到调节。HERV 的表达在生理和病理条件下发生，在一个或多个身体部位。几种疾病归因于一种或多种 HERV，特别是神经疾病。关键问题是将 HERV 的表达区分为疾病的原因或结果。为了用作生物标志物，必须找到特定 HERV 的表达与疾病发作和/或行为之间的相关性。更大的挑战是建立致病作用。定义 HERV 与疾病之间因果关系的标准包括开发动物模型，以及通过抗 HERV 治疗性抗体在人类中调节疾病。到目前为止，已经在 HERV-W 和多发性硬化症之间实现了 HERV 与疾病之间的统计学显著相关性；已经在转基因动物中实现了 HERV-W 和多发性硬化症以及 HERV-K 和肌萎缩侧索硬化症的疾病再现。这两种疾病的临床试验都在进行中。
