Does the interplay between human endogenous retrovirus K and extracellular vesicles contribute to aging?

Catherine DeMarino, Avindra Nath, Zhengping Zhuang, Tara T. Doucet-O’Hare
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Abstract

The role of extracellular vesicles (EVs), including retroviral-like particles (RVLPs), in pathogenic processes is currently a subject of active investigation. Several studies have identified mechanistic links between the increased presence of EVs and the process of senescence. A recent study reveals that the reverse transcribed complementary DNA (cDNA) of a human endogenous retroviral sequence can activate the innate immune system and result in tissue damage and/or the spread of cellular senescence to distant tissues. Several studies have linked EVs to age-related diseases, such as Alzheimer’s disease and Parkinson’s disease, and have included isolation of EVs from individuals with these diseases. Loss of epigenetic regulation, immune activation, and environmental stimuli can all lead to the expression of endogenous retroviruses and the incorporation of their proteins and transcripts into EVs. In addition, EVs disseminating these endogenous retroviral components have now been shown to act in a paracrine manner in multiple human diseases. Further investigation of the connection between EVs containing endogenous retroviral protein products or nucleotides should be pursued in models of age-related diseases.
人内源性逆转录病毒K与细胞外囊泡之间的相互作用是否有助于衰老?
细胞外囊泡(EVs),包括逆转录病毒样颗粒(rvlp),在致病过程中的作用目前是一个积极研究的主题。几项研究已经确定了ev增加与衰老过程之间的机制联系。最近的一项研究表明,人类内源性逆转录病毒序列的逆转录互补DNA (cDNA)可以激活先天免疫系统,导致组织损伤和/或细胞衰老向远处组织扩散。几项研究已将ev与年龄相关疾病(如阿尔茨海默病和帕金森病)联系起来,并从患有这些疾病的个体中分离出ev。表观遗传调控的缺失、免疫激活和环境刺激都可能导致内源性逆转录病毒的表达及其蛋白和转录物进入ev。此外,传播这些内源性逆转录病毒成分的ev现在已被证明在多种人类疾病中以旁分泌方式起作用。应在年龄相关疾病模型中进一步研究含有内源性逆转录病毒蛋白产物或核苷酸的ev之间的联系。
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