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• W159081618 abstract "Highly active anti-retroviral treatment (HAART) targets less than a third of the proteinsproduced during HIV-1 infection. Testing the effectiveness of an anti-retroviral drug requiresassays specific for the individual target that take into account its mechanism of action. MostHIV-1 proteins need to undergo dimerization in order to become functional in the viral life cycle. Historically, it has been difficult to visualize and quantify changes in a protein-protein interaction, which has left this characteristic of proteins unexplored as potential antiviral targets. In this study, a bimolecular fluorescence complementation based screening assay is developed that can quantify a change in dimerization, using the HIV-1 accessory protein Vpr as a proof of concept.Results demonstrated that bimolecular fluorescence complementation of Vpr could be competed off in a dose-dependent manner using untagged, full length Vpr as a competitor molecule. The change in signal intensity was measured quantitatively through flow cytometry and fluorescence microscopy in a high content screening assay. High content imaging was used to screen a library of peptides and a library of small molecules for an effect on Vpr dimerization. None of the Vpr peptides were shown to have an effect; however, one of the small molecules was shown to interfere with Vpr dimerization in a dose-dependent manner.Statement of Public Health relevance: Dimerization is a unique property of many HIV-1 viral proteins and is necessary to complete the viral life cycle, thus it has been identified as a potential drug target. By developing an assay that screens for inhibition of HIV-1 protein dimerization, high throughput screening can be performed to detect inhibitors of a new target in HIV-1 replication. Small molecules identified using this screening method could be developed into a novel anti-retroviral drug." @default.
• W159081618 created "2016-06-24" @default.
• W159081618 creator A5049080163 @default.
• W159081618 date "2011-06-29" @default.
• W159081618 modified "2023-09-27" @default.
• W159081618 title "Development of a high throughput cell-based assay to screen for inhibitors of HIV-1 Vpr oligomerization" @default.
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• W159081618 hasPublicationYear "2011" @default.
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