Università Vita-Salute San Raffaele
Università Vita-Salute San Raffaele
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Marina Lusic

Research Activity

I am interested in unraveling the molecular mechanisms involved in the establishment of latent viral reservoirs, as well as in those that lead to the escape from latency. Latent reservoirs, established within days following acute HIV infection are continuously repopulated troughout the course of active viral replication, have an extremely long half life and could hardly be cleared even after 50 years of antiviral therapy. Among mechanisms proposed to contribute to the establishment of viral latency are repressive chromatin environment, the lack of action of key host factors and a failure of viral Tat transactivator protein to act.

My research activity  focuses on the role of chromatin in regulation of HIV-1 gene expression.  The property of viral Tat protein to recruit histone acetyltransferase (HAT) p300 to the viral promoter served as a basis for the studies of epigenetic changes at the viral promoter in the course of reactivation from latency. We have contributed to describing the recruitment to the integrated viral promoter of a truncated form of STAT5 protein that exerts a repressive role on viral transcription (Crotti et al. Blood 2007). By exploring the same model of viral latency we have described the presence along the silent viral genome of a posttranslationally modified kinase component of P-TEFb (CDK9), one of the most important cellular transcriptional partners of HIV-1 (Sabo’ et al. MCB 2008). Since AcCDK9 resides within the PML nuclear bodies we hypothesized that PML nuclear bodies or some other specific nuclear compartments harbour the silent virus. Moreover, we have recently described that HIV-1 provirus undergoes a peculiar structural change when exiting from latency. This looping structure achieved by juxtaposition of the two LTRs only when the virus is activelly transcribing, depends on both the viral sequences and on the neighbouring chromatin (Perkins et al. Mol Cell 2008)