Non-coding RNAs and HIV-1 latency (360G-Wellcome-097427_Z_11_Z)

After decades of research, overcoming HIV-1 post-integration latency remains imperative. When HIV-1 genome integrates into the host, it behaves as a mammalian gene and it is subject to the same mechanisms controlling host gene expression. Gene silencing is a complex and multifactorial process that can beepigenetically mediated, involving steps such as chromatin remodelling, DNA methylation and histone modifications. Non-coding RNAs (ncRNAs) are well established players in this process at the host level, however, its role in HIV-1 proviral silencing is yet to be described. This project aims to address this gap and, combining in silico techniques with molecular virology based assays, explore ncRNA species role in HIV-1 post-integration latency. We will begin with in silico screening for ncRNAs that demonstrate sequence specific affinity to the HIV-1 promoter. After selection, the most promising candidates will go into function validation assays and their effect on HIV-1 transcription will be assessed. Following, wewill experimentally validate 5'LTR sequence targeting and carry out a