Fleta Soriano, Eric, 1983-Martinez, Javier P.Hinkelmann, BettinaGerth, KlausWashausen, PeterDíez Antón, Juana, 1962-Frank, RonaldSasse, FlorenzMeyerhans, Andreas2015-03-192015-03-192014Fleta-Soriano E, Martinez JP, Hinkelmann B, Gerth K, Washausen P, Diez J, Frank R, Sasse F, Meyerhans A. The myxobacterial metabolite ratjadone A inhibits HIV infection by blocking the Rev/CRM1-mediated nuclear export pathway. Microbial Cell Factories. 2014; 13: 17. DOI 10.1186/1475-2859-13-171475-2859http://hdl.handle.net/10230/23228Background: The nuclear export of unspliced and partially spliced HIV-1 mRNA is mediated by the recognition of a leucine-rich nuclear export signal (NES) in the HIV Rev protein by the host protein CRM1/Exportin1. This makes the CRM1-Rev complex an attractive target for the development of new antiviral drugs. Here we tested the anti-HIV efficacy of ratjadone A, a CRM1 inhibitor derived from myxobacteria. Results: Ratjadone A inhibits HIV infection in vitro in a dose-dependent manner with EC50 values at the nanomolar range. The inhibitory effect of ratjadone A occurs around 12 hours post-infection and is specific for the Rev/CRM1-mediated nuclear export pathway. By using a drug affinity responsive target stability (DARTS) assay we could demonstrate that ratjadone A interferes with the formation of the CRM1-Rev-NES complex by binding to CRM1 but not to Rev. Conclusion: Ratjadone A exhibits strong anti-HIV activity but low selectivity due to toxic effects. Although this limits its potential use as a therapeutic drug, further studies with derivatives of ratjadones might help to overcome these difficulties in the future.application/pdfeng© 2014 Fleta-Soriano et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.RNA missatgerVIH (Virus)Immunodeficiènciainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/1475-2859-13-17RatjadoneMyxobacteriaHIVRevHost factorCRM1Nuclear exportinfo:eu-repo/semantics/openAccess