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Vif-induced APOBEC3G degradation as a novel drug target for therapeutics in HIV
Högskolan i Skövde, Institutionen för vård och natur.
2012 (engelsk)Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
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.

sted, utgiver, år, opplag, sider
2012. , s. 24
Emneord [en]
HIV, APOBEC, Vif, ElonginC, BiFC.
HSV kategori
Identifikatorer
URN: urn:nbn:se:his:diva-5881OAI: oai:DiVA.org:his-5881DiVA, id: diva2:527159
Eksternt samarbeid
UNIVERSITÄT WÜRZBURG, Germany
Fag / kurs
Molecular Biology
Utdanningsprogram
Molekular Biology - Master's Programme
Presentation
2012-05-01, P 201, Portalen.Kanikegränd 3A,, Skövde, Sweden, 09:00 (engelsk)
Uppsök
Life Earth Science
Veileder
Examiner
Tilgjengelig fra: 2012-05-28 Laget: 2012-05-17 Sist oppdatert: 2012-05-28bibliografisk kontrollert

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