Human endogenous retroviruses (HERVs) are abundant sequences that persist within the human genome as remnants of ancient retroviral infections. These sequences became fixed and accumulate mutations or deletions over time. HERVs have affected human evolution and physiology by providing a unique repertoire of coding and non-coding sequences to the genome. In healthy individuals, HERVs participate in immune responses, formation of syncytiotrophoblasts and cell-fate specification. In this Review, we discuss how endogenized retroviral motifs and regulatory sequences have been co-opted into human physiology and how they are tightly regulated. Infections and mutations can derail this regulation, leading to differential HERV expression, which may contribute to pathologies including neurodegeneration, pathological inflammation and oncogenesis. Emerging evidence demonstrates that HERVs are crucial to human health and represent an understudied facet of many diseases, and we therefore argue that investigating their fundamental properties could improve existing therapies and help develop novel therapeutic strategies.

人类内源性逆转录病毒（HERV）是作为古代逆转录病毒感染的残余物存在于人类基因组中的丰富序列。这些序列变得固定并随着时间的推移积累突变或缺失。HERV 通过为基因组提供独特的编码和非编码序列，影响了人类的进化和生理学。在健康个体中，HERV 参与免疫反应、合体滋养细胞的形成和细胞命运规范。在这篇综述中，我们讨论了内源性逆转录病毒基序和调控序列如何被纳入人类生理学以及它们如何受到严格调控。感染和突变可能会破坏这种调节，导致 HERV 表达差异，这可能导致神经退行性变、病理性炎症和肿瘤发生等病理学。新的证据表明，HERV 对人类健康至关重要，并且代表了许多疾病的一个未被充分研究的方面，因此我们认为，研究其基本特性可以改善现有疗法并有助于开发新的治疗策略。