PML/TRIM19-dependent inhibition of HIV-1 reverse-transcription by Daxx Jacques DUTRIEUX PhD. INSERM U941 – Saint Louis Hospital Paris, FRANCE Contact: jacques.dutrieux@inserm.fr PML/TRIM19-dependent inhibition of HIV-1 reverse-transcription by Daxx DUTRIEUX J. et al., PLOS Pathogens 2015 Good afternoon, I will present you the work I’ve done during my PhD in Rémi Cheynier’s lab at the Institut Cochin in Paris where I’ve studied the impact of acute SIV infection on thymopoiesis in rhesus macaques. INSERM UMR-S 1124 Team « Mechanism of interferon action and biotherapeutic pathways » Sébastien NISOLE & Mounira K. CHELBI ALIX Paris, FRANCE

Promyelocytic Leukemia protein inhibits HIV-1 infection Day post-infection p24 (ng/ml) shRNA CTR shRNA PML Mock PBMC MEF MOI wt PML KO PML KO + As2O3 wt + As2O3 GFP-positive cells (%) HIV-1 infection is enhanced in absence of PML Uninfected HIV-1 10 µm PML p24 Retroviral infections triggers a transitory formation of PML cytoplasmic bodies

Daxx is the protein responsible for HIV-1 restriction GFP-positive cells (%) 0.01 0.1 1 10 MOI wt Daxx KO MEF Day post-infection p24 (ng/ml) EV Daxx Mock PBMC HIV-1 infection is enhanced in absence of Daxx and reduced when Daxx is over-expressed Mock HIV-1 10 µm Daxx co-localizes with the incoming HIV-1 capsids Daxx Actin wt PML KO Sp100 MEF 1 0.5 1.5 Daxx / RPL13A shRNA CTR PML shRNA PML MG132 - + HeLa PML is necessary for Daxx expression and stabilization

In presence of PML No PML What triggers Daxx degradation ? What triggers PML CBs formation? How Daxx inhibit Reverse Transcription ? What are the constituents of PML CBs ?