Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts

G HIV-1 Tat function. We have long been intrigued by the
G HIV-1 Tat function. We have long been intrigued by the peculiar property of the protein to be released by the cells through a non-canonical, ER-Golgiindependent protein secretion pathway and to enter neighboring cells, where it is transported to the nucleus in a transcriptionally active form. Of note, fusion of heterologus proteins to the Tat basic domain also imparts these proteins the intercellular trafficking capacity of the wild type protein. By assessing the effect of a series of metabolic inhibitors on leaderless Tat release, we have now mapped the relevant cellular interactions mediating extracellular Tat release.Page 1 of(page number not for citation purposes)
RetrovirologyInvited speaker presentationBioMed CentralOpen AccessDynamic interplay between HIV-1 integrase and host cofactorsSt PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28945807 hane EmilianiAddress: Institut Cochin, Universit?Paris Descartes, CNRS (UMR 8104), Paris, France. Inserm, U567, Paris, France from Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts Montpellier, France. 21-23 September 2009 Published: 24 September 2009 Retrovirology 2009, 6(Suppl 2):I14 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27607577 doi:10.1186/1742-4690-6-S2-I Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here. http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf This abstract is available from: http://www.retrovirology.com/content/6/S2/I14 ?2009 Emiliani; licensee BioMed Central Ltd.Due to its limited genomic capacity, HIV-1 must interact with several cellular partners to replicate. Integration of a cDNA copy of its RNA genome into a chromosome of the host cell is a key step of retroviral replication that is under the control of Integrase. Although, the recombinant integrase is necessary and sufficient to catalyze the integration reaction in vitro, numerous studies have showed that cellular cofactors of integrase are involved in viral replication. Large-scale yeast two-hybrid screening (y2HS) has been proven to be a powerful approach to identify new protein-protein interactions. Using this method, we were able to isolate several new host cofactors interacting with integrase. Together, our studies have identified the human lens epithelium-derived growth factor (LEDGF/p75), Transportin-SR2 (TNPO3), and von Hippel-Lindau binding protein 1 (VBP1) as cellular binding partners of HIV-1 integrase. For these cell factors, we have generated and characterized loss of affinity mutants of integrase, which, when R1503 clinical trials combined with viral functional assays, validated their involvement in early step of the HIV-1 replication cycle. Using a biochemical approach to follow PIC components in different cellular compartments, the dynamic interaction between integrase and cellular cofactors was further explored within infected cells. Cellular cofactors are required for the completion of the HIV replication cycle and it is critical to elucidate on their mechanism of action. Novel therapeutic strategies aim to develop antiviral compounds targeting interactions between integrase and host-cell partners. Such novel targets are continuously needed to overcome the problem linked to the somewhat frequent occurrence of multi-drug-resistance, that in turn leads to complete therapeutic failure for patients infec.