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Expression of CircRNAs in HIV infection and latency

HIV感染和潜伏期中CircRNA的表达

基本信息

批准号：
10239083
负责人：
Miguel De Mulder Rougvie
金额：
$ 21.19万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-14 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10239083
关键词：
Aging Antiviral Agents Basic Science Binding Sites Bioinformatics Biological Markers Brain Cell Proliferation Cell division Cells Characteristics Communicable Diseases Complex Data Data Analyses Disease Disease Outbreaks Down-Regulation Gene Expression Genetic Transcription Goals HIV HIV Infections HIV-1 Health Human Immune response In Vitro Indiana Infection Innate Immune Response Innate Immune System Knowledge Link Location Measures Mediating Messenger RNA Methods MicroRNAs Modeling Morbidity - disease rate Outcomes Research Pattern Poly(A) Tail Porifera Prevention Measures Process Proteins RNA RNA-Binding Proteins Reporting Rest Role Synapses T-Lymphocyte Therapeutic Time Tissues Translating Virus Diseases Virus Latency antiretroviral therapy base circular RNA digital enzyme substrate experience immunoregulation innovation intravenous drug use mortality neurogenesis novel pluripotency potential biomarker protein function reactivation from latency recruit response scaffold therapy design transcriptome sequencing transcriptomics virology

项目摘要

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.

项目总结/摘要环状RNA（Circular RNA，circRNA）是一类单链共价闭合的RNA，缺乏经典的特征如5'帽和3'聚腺苷酸尾。CircRNA表达模式对病毒感染敏感和细胞分裂率，这使我们能够提出circRNA可能参与感染的假设和HIV-1的潜伏状态。HIV-1仍然是世界上最重要的传染病之一，尽管尽管进行了大量的尝试，但尚未找到治愈方法。大多数HIV-1的转录组学研究都集中在 RNA种类，如信使RNA或微RNA，但在早期和晚期表达circRNA 除了抗逆转录病毒治疗（ART）的反应外，感染的风险仍然未知。而且阻碍HIV-1根除的主要障碍是一小部分潜伏感染的静息T细胞，抗逆转录病毒疗法，并可能产生新的感染浪潮。CircRNA可以作为潜伏的HIV-1细胞的生物标志物，在HIV-1重新激活的过程中，对于踢和杀死或阻止和锁定HIV-1根除战略至关重要。在这里，我们将鉴定出与HIV-1感染早期和晚期有关的circRNA， circRNA参与潜伏期。此外，几种ART和潜伏期逆转剂对将探索circRNA的表达。作为初步结果，我们分析了两个不同时间的数据，点在HIV-1感染和从体外HIV-1潜伏期模型。HIV-1感染后的时间感染显示circRNA表达随时间的差异。另一方面，体外实验的结果表明， HIV-1潜伏期模型显示，在潜伏期再激活后，circRNA显著下调， circRNA作为HIV-1潜伏细胞的潜在生物标志物。结果将增加对HIV-1病毒感染的认识此外，circRNA可能指向新的细胞RNA的鉴定，发现或设计控制HIV-1感染和潜伏期的干预措施的目标。