The role of the viral protein Vpr in the epigenetic regulation of HIV-1 latency 

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B995
Abstract ID: 5405

Presenting Author:
Catherine A Lewis , Graduate Student at Univ. of North Carolina, Chapel Hill

Abstract:

The primary obstacle to HIV-1 cure is the persistence of a long-lived latent reservoir, best characterized in memory CD4⁺ T cells. New research supports latency prevention as a therapeutic strategy. However, such an approach will require a better understanding of how HIV-1 establishes latency. We recently showed that histone deacetylases (HDACs) are critical for entry into latency. Whether HDACs interact with specific viral factors, particularly the HIV-1 accessory protein and coactivator Vpr, to regulate latency establishment is unknown. We therefore sought to determine how Vpr, both alone and in combination with the HDAC inhibitor vorinostat (VOR), regulates HIV-1 latency establishment. In a primary CD4⁺ T-cell model, we observed a p300-dependent synergy between Vpr and VOR in maintaining viral gene expression. We next assessed whether Vpr delivery during latent infection, a stage when viral proteins are not normally expressed, could enhance the ability of VOR alone to induce viral gene expression. We found that Vpr delivery reactivated latently infected CD4⁺ T cells to a greater extent than VOR treatment alone and that the combination of Vpr delivery and VOR treatment led to the highest level of reactivation. An improved understanding of how host and viral factors interact during HIV-1 latency establishment in CD4⁺ T cells will aid in the development of new therapies that prevent HIV-1 entry into the latent reservoir or that reverse latency in latently infected cells.