Expression of CircRNAs in HIV infection and latency

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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.