Expression of CircRNAs in HIV infection and latency

项目摘要/摘要 环状RNA(CircRNAs)是一种单链共价闭合RNA，缺乏经典的特性 如5‘帽和3’多聚-A尾巴等线形mRNA。CircRNAs的表达模式对病毒感染敏感 和细胞分裂率，这允许我们提出CircRNAs可能参与感染的假设 和HIV-1的潜伏期。HIV-1仍然是世界上最严重的传染病之一，尽管 尽管进行了大量的尝试，但仍未找到治愈的方法。HIV-1的大多数转录转录研究都集中在 RNA种类，如信使RNA或微型RNA，但CircRNAs在早期和晚期的表达 除了对抗逆转录病毒疗法(ART)的反应外，感染的可能性仍不清楚。此外， 阻碍HIV-1根除的主要障碍是潜伏感染的静息T细胞的小储备库，这些T细胞在 ART和可以催生新的感染浪潮。CircRNAs可以作为潜伏的HIV-1细胞的生物标志物 在艾滋病毒-1重新激活过程中发挥重要作用，这对于踢杀或阻止并锁定艾滋病毒-1根除战略来说是重要的。 在这里，我们将确定除了在HIV-1感染的早期和晚期所起的作用外，在HIV-1感染的早期和晚期所涉及的CircRNA CircRNAs参与了潜伏期。此外，几种ART和潜伏期反转剂对 将探索CircRNAs的表达。作为初步结果，我们分析了两个不同时间的数据 在HIV-1感染期间和体外HIV-1潜伏期模型中的点数。关于HIV-1之后的时间的结果 感染后CircRNA的表达随时间的变化而不同。另一方面，体外培养的结果 HIV-1潜伏期模型显示潜伏期重新激活后CircRNAs显著下调，以及两个 CircRNA可作为HIV-1潜伏细胞的潜在生物标志物。结果将增加对HIV-1病毒感染的了解 以及对它的先天免疫反应。此外，CircRNAs可能指向新的细胞RNAs的鉴定 发现或设计控制HIV-1感染和潜伏的干预措施的目标。

PROJECT SUMMARY/ABSTRACT Circular RNAs (circRNAs) are single stranded covalently closed RNAs, which lack the classical characteristics of linear mRNA such as 5’ cap and 3’ poly-A tails. CircRNAs expression patterns are sensitive to viral infection and cell division rates, which allows us to propose the hypothesis that circRNAs might be involved in infection and latency state of HIV-1. HIV-1 is still one of the world’s most significant infectious diseases and, despite the vast attempts, its cure has not been found. Most of the transcriptomic studies in HIV-1 have been focused on RNA species, like messengers RNAs or micro RNA but the expression of circRNAs during early and late stages of infections in addition to their response to antiretroviral therapy (ART) remains unknown. Furthermore, the major barrier impeding HIV-1 eradication is a small reservoir of latently infected resting T-cells that persist after ART and can spawn new waves of infection. CircRNAs could serve as biomarkers for latent HIV-1 cells or could be important in processes of HIV-1 reactivation, for the kick and kill or block and lock HIV-1 eradication strategy. Here we will identify circRNAs implicated in early and late stages of HIV-1 infection in addition to the role of circRNAs involved in latency. Additionally, the effect of several ARTs and latency reversal agents on the expression of circRNAs will be explored. As preliminary results, we have analyzed data from two different time points during HIV-1 infection and from an in vitro HIV-1 latency model. The results on the time after HIV-1 infection showed differences of circRNA expression through time. On the other hand, the results of the in vitro HIV-1 latency model showed a significant downregulation of circRNAs after latency reactivation, and two circRNAs as potential biomarkers of HIV-1 latent cell. Results will increase the knowledge on HIV-1 viral infection and innate immune response to it. Additionally, circRNAs might point to the identification of novel cellular RNAs targets for discovery or design interventions that control HIV-1 infection and latency.