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Vif-induced APOBEC3G degradation as a novel drug target for therapeutics in HIV
University of Skövde, School of Life Sciences.
2012 (English)Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC3G) a cellular host defence factor known for its antiviral activity for HIV-1. The potency of APOBEC3G is greatly reduced due to its interaction with viral infectivity factor (Vif) encoded by HIV-1. The interaction of APOBEC3G with Vif is via the SCF-like E3 ubiquitin ligase comprising of Cullin5 and Elongins B and C through a SOCS (suppressor of cytokine signalling box)-box, which binds to Elongin C leading to degradation of APOBEC3G via the ubiquitin proteosome pathway. The interaction between ElonginC and SOCS box harbouring Vif may serve as a therapeutic target on which Bimolecular fluorescence complementation assay (BiFC) was designed. A transient and optimized cellular testing platform was established for high-throughput screening of potential antiviral compound libraries. The plasmids were designed wherein the fluorescent fragment Venus, was linked to Vif and Elongin C. The BiFC test system was validated using well characterised mutants of Vif and ElonginC based on fluorescence complementation. The quantification of the Vif-ElonginC interaction was done with BiFC where rationally designed compounds were screened. A small molecule FM173 was identified to be inhibiting the Vif-Elongin C interaction using this cellular assay. Taken together, an effective screening platform was established with screening assay quality factor (Z factor) of 0.52 making it an excellent assay for identification of novel anti-retroviral agents based on the Vif-ElonginC interaction.

Place, publisher, year, edition, pages
2012. , 24 p.
Keyword [en]
HIV, APOBEC, Vif, ElonginC, BiFC.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:his:diva-5881OAI: oai:DiVA.org:his-5881DiVA: diva2:527159
Subject / course
Molecular Biology
Educational program
Molekular Biology - Master's Programme
Presentation
2012-05-01, P 201, Portalen.Kanikegränd 3A,, Skövde, Sweden, 09:00 (English)
Uppsok
Life Earth Science
Supervisors
Examiners
Available from: 2012-05-28 Created: 2012-05-17 Last updated: 2012-05-28Bibliographically approved

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CiteExportLink to record
Permanent link

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Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
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