Mode of action of MATR3, PTB, PSF and HIV reactivation; Discovery of new host factors implicated in HIV-1 RNA nuclear export and HIV-1 post-transcriptional silencing; Select drugs to be validated in WP5

Define the mode of action of MATR3, PTB, PSF on HIV RNA nuclear export. Exploiting shRNA and CRISPR/Cas9 systems we will explore MATR3 mutants and assess their behaviour by functional assays including monitoring of HIV RNA nuclear export by live imaging. Live imaging will be complemented by studies at NUID UCD. Develop an unbiased high-throughput assay for the identification of other potential post-transcriptional blocks of HIV reactivation, which include nuclear export of HIV RNA, translation and packaging. Test and select new latency-reversible compounds targeting functionally host proteins involved in post-transcriptional HIV-1 silencing using in vitro latency models.