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Project

Single virus live imaging of HIV nuclear import and integration

To date, 38 million people worldwide have been infected with the human immunodeficiency virus type 1 (HIV-1). Antiretroviral therapy can suppress HIV-1 replication and prevent the onset of acquired immune deficiency syndrome (AIDS). Treatment is lifelong as the virus reappears from reservoirs after interruption of therapy. Understanding the interactions between the host and the viral proteins during the replication cycle is vital to develop new strategies for an HIV cure. In this research proposal, we use a state-of-the-art imaging platform to study the early replication steps of HIV at a single virus level using confocal microscopy of virus labeled with eGFP integrase. We will characterize HIV particles entering the nucleus using expansion microscopy. We will next investigate the role of the transportins 1 and SR2 (TNPO1/TRN-SR2) in the nuclear import of HIV. Several parameters, such as nuclear import efficiency, nuclear localization and the HIV integrase (IN) oligomerization state will be determined after depletion of transportin or by using an interaction-defective mutant of TRN-SR2. Finally, we will study the relationship between integration site selection and HIV transcript levels via bDNA imaging. This research will contribute to new strategies for the functional cure of HIV infection.

Date:1 Jan 2022 →  Today
Keywords:HIV-1, early replication steps, expansion microscopy
Disciplines:Virology, Intracellular compartments and transport