Program of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA), University of Navarra (UNAV), 31008 Pamplona, Spain.
Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.
Int J Mol Sci. 2020 Sep 3;21(17):6447. doi: 10.3390/ijms21176447.
The proper functioning of the immune system requires a robust control over a delicate equilibrium between an ineffective response and immune overactivation. Poor responses to viral insults may lead to chronic or overwhelming infection, whereas unrestrained activation can cause autoimmune diseases and cancer. Control over the magnitude and duration of the antiviral immune response is exerted by a finely tuned positive or negative regulation at the DNA, RNA, and protein level of members of the type I interferon (IFN) signaling pathways and on the expression and activity of antiviral and proinflammatory factors. As summarized in this review, committed research during the last decade has shown that several of these processes are exquisitely regulated by long non-coding RNAs (lncRNAs), transcripts with poor coding capacity, but highly versatile functions. After infection, viruses, and the antiviral response they trigger, deregulate the expression of a subset of specific lncRNAs that function to promote or repress viral replication by inactivating or potentiating the antiviral response, respectively. These IFN-related lncRNAs are also highly tissue- and cell-type-specific, rendering them as promising biomarkers or therapeutic candidates to modulate specific stages of the antiviral immune response with fewer adverse effects.
免疫系统的正常运作需要在无效反应和免疫过度激活之间的微妙平衡中进行强有力的控制。对病毒侵袭的反应不佳可能导致慢性或压倒性感染，而不受控制的激活会导致自身免疫性疾病和癌症。对抗病毒免疫反应的幅度和持续时间的控制是通过在 I 型干扰素 (IFN) 信号通路成员的 DNA、RNA 和蛋白质水平以及抗病毒和促炎因子的表达和活性上进行精细的正或负调节来实现的。正如本综述所总结的，过去十年的深入研究表明，这些过程中的许多过程都受到长非编码 RNA (lncRNA) 的精细调控，lncRNA 是一种编码能力差但功能多样的转录本。感染后，病毒及其引发的抗病毒反应会下调一组特定的 lncRNA 的表达，这些 lncRNA 的功能分别通过使抗病毒反应失活或增强来促进或抑制病毒复制。这些 IFN 相关的 lncRNA 也具有高度的组织和细胞类型特异性，使它们成为有前途的生物标志物或治疗候选物，可以在较少产生不良反应的情况下调节抗病毒免疫反应的特定阶段。
