| Literature DB >> 27127234 |
Alex Rialdi1,2, Laura Campisi1,2, Nan Zhao1,2, Arvin Cesar Lagda1,2, Colette Pietzsch3, Jessica Sook Yuin Ho4, Luis Martinez-Gil1,5, Romain Fenouil6, Xiaoting Chen7, Megan Edwards1, Giorgi Metreveli1,2, Stefan Jordan8, Zuleyma Peralta6, Cesar Munoz-Fontela9, Nicole Bouvier1, Miriam Merad8, Jian Jin10, Matthew Weirauch7, Sven Heinz11,12, Chris Benner12, Harm van Bakel6, Christopher Basler1, Adolfo García-Sastre1,2, Alexander Bukreyev3, Ivan Marazzi1,2.
Abstract
The host innate immune response is the first line of defense against pathogens and is orchestrated by the concerted expression of genes induced by microbial stimuli. Deregulated expression of these genes is linked to the initiation and progression of diseases associated with exacerbated inflammation. We identified topoisomerase 1 (Top1) as a positive regulator of RNA polymerase II transcriptional activity at pathogen-induced genes. Depletion or chemical inhibition of Top1 suppresses the host response against influenza and Ebola viruses as well as bacterial products. Therapeutic pharmacological inhibition of Top1 protected mice from death in experimental models of lethal inflammation. Our results indicate that Top1 inhibition could be used as therapy against life-threatening infections characterized by an acutely exacerbated immune response.Entities:
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Year: 2016 PMID： 27127234 PMCID： PMC5193222 DOI： 10.1126/science.aad7993
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728