An endogenous retroviral element exerts an antiviral innate immune function via the derived lncRNA lnc-ALVE1-AS1
An endogenous retroviral element exerts an antiviral innate immune function via the derived lncRNA lnc-ALVE1-AS1
复制标题
内源性逆转录病毒元件通过衍生的 lncRNA lnc-ALVE1-AS1 发挥抗病毒先天免疫功能。
DOI：
10.1016/j.antiviral.2019.104571
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发表时间：
2019-10-01
影响因子：
7.6
通讯作者：
Cui, Hengmi
中科院分区：
文献类型：
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作者：
Chen, Shihao;Hu, Xuming;Cui, Hengmi
内源性逆转录病毒（erv）是动物和人类基因组的重要组成部分，在成年细胞中通常通过表观遗传机制被沉默。尽管最近有报道称erv与早期发育、肿瘤发生和自身免疫性疾病有关，但它们对抗病毒先天免疫的影响及其潜在机制尚未阐明。在这里，我们提供了内源性逆转录病毒元件通过其衍生的反义长非编码RNA （lncRNA）影响抗病毒先天免疫的第一个直接证据。我们发现，从1号染色体上的内源性禽白血病病毒（ALVE1）转录而来的反义lncRNA -ALVE1- as1，明显抑制外源性逆转录病毒在鸡胚成纤维细胞（CEFs）中的进入和复制。这种行为至少部分归因于ALVE1激活诱导抗病毒先天免疫途径，这表明激活的内源性逆转录病毒元件可能通过其衍生的反义lncRNA诱导抗病毒防御反应。我们还发现lnc-ALVE1-AS1通过激活细胞质中的TLR3信号介导这些作用。我们的研究结果对erv的抗病毒先天免疫功能提供了新的见解，表明erv可能在抗病毒防御中发挥重要作用，并为新疫苗的开发提供了新的策略。
Endogenous retroviruses (ERVs) constitute an important component of animal and human genomes and are usually silenced by epigenetic mechanisms in adult cells. Although ERVs were recently reported to be linked to early development, tumorigenesis and autoimmune disease, their impacts on antiviral innate immunity and the underlying mechanisms have not been elucidated. Here, we provide the first direct evidence of an endogenous retroviral element affecting antiviral innate immunity via its derived antisense long non-coding RNA (lncRNA). We found that an antisense lncRNA, which is called lnc-ALVE1-AS1 and is transcribed from the endogenous avian leukosis virus in chromosome 1 (ALVE1), distinctly inhibited the entry and replication of exogenous retroviruses in chicken embryonic fibroblasts (CEFs). This behaviour is at least in part attributed to the induction of an antiviral innate immune pathway by ALVE1 activation, suggesting that an activated endogenous retroviral element may induce antiviral defence responses via its derived antisense lncRNA. We also found that lnc-ALVE1-AS1 mediated these effects by activating the TLR3 signalling in the cytoplasm. Our results provide novel insights into the antiviral innate immune function of ERVs, suggesting that ERVs may play an important role in antiviral defences and provide new strategies for the development of new vaccines.