2006 International Meeting of The Institute of Human Virology

Etroviral infection and in HIV-1 infected subjects. MK-0518 is the most
Etroviral infection and in HIV-1 infected subjects. MK-0518 is the most advanced of the clinical candidates in this new class. MK-0518 has demonstrated robust efficacy in short term monotherapy studies and in phase 2 combinations studies in treatment PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26740125 na e subjects and in patients with multi-class resistance. Although the first integrase inhibitors are still in clinical development, insights from the study of integrase function and inhibitor mechanism of action as well as observations from clinical and animal studies suggest ML390 chemical information important PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28380356 implications for the development of this new antiretroviral class and the effect of these agents on HIV-1 infection.Page 1 of(page number not for citation purposes)
RetrovirologyOral presentationBioMed CentralOpen AccessTranscription factor binding aites in the pol gene intragenic regulatory region of HIV-1 are important for virus infectivitySt hane de Walque, Caroline Vanhulle, Nathalie Vandenhoudt, Beno Van Driessche, Ars e Burny and Carine Van Lint*Address: Laboratory of Molecular Virology, University of Brussels, 6041 Gosselies, Belgium Email: Carine Van Lint* – [email protected] * Corresponding authorfrom 2006 International Meeting of The Institute of Human Virology Baltimore, USA. 17?1 November, 2006 Published: 21 December 2006 Retrovirology 2006, 3(Suppl 1):S41 doi:10.1186/1742-4690-3-S1-S Meeting abstracts. A single PDF containing all abstracts in this Supplement is available here http://www.biomedcentral.com/content/pdf/1742-4690-3-S1-info.pdf?2006 de Walque et al; licensee BioMed Central Ltd.We have previously identified in the pol gene of HIV-1 a new positive transcriptional regulatory element associated with a nuclease-hypersensitive site (HS7) and containing recognition sites for nuclear proteins [1]. We have next further physically characterized each binding site and have shown that the transcription factors Oct-1, Oct-2, PU.1, Sp1 and Sp3 interact in vitro with the pol region. Chromatin immunoprecipitation assays using HIVinfected cell lines demonstrated that Sp1, Sp3, Oct1 and PU.1 are recruited to the HS7 region in vivo. For each site, we have identified mutations abolishing factor binding to their cognate DNA sequences without altering the underlying amino acid sequence of the integrase. By transient transfection assays, we have demonstrated the involvement of the pol binding sites in the transcriptional enhancing activity of the intragenic region. Our functional results with multimerized wild-type and mutated pol binding sites separately have demonstrated that the PU.1, Sp1, Sp3 and Oct-1 transcription factors regulate the transcriptional activity of a heterologous promoter through their respective HS7 binding sites. Finally, we have investigated the physiological role of the HS7 binding sites in HIV-1 replication and have shown that these sites are important for viral infectivity [2]. Current studies are examining the role of AP-1 binding sites located upstream of the HS7 region in the enhancer activity and in the viral replication cycle.
RetrovirologyResearchBioMed CentralOpen AccessHIV-1 integrase inhibitors are substrates for the multidrug transporter MDR1-P-glycoproteinMaurizio Cianfriglia*1, Maria Luisa Dupuis1, Agnese Molinari1, Antonio Verdoliva2, Roberta Costi3, C.