Journal article
Topoisomerase 1 inhibition promotes cyclic GMP-AMP synthase-dependent antiviral responses
G Pépin, C Nejad, J Ferrand, BJ Thomas, HJ Stunden, E Sanij, CH Foo, CR Stewart, JE Cain, PG Bardin, BRG Williams, MP Gantier
Mbio | AMER SOC MICROBIOLOGY | Published : 2017
Abstract
Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS) detection of cytoplasmic DNA. This argues against CPT having only anti-inflammatory activity. Furthermore, expression of the simian virus 40 (SV40) large T antigen was paramount to t..
View full abstractGrants
Awarded by Fonds de Recherche du Québec - Santé
Funding Acknowledgements
This work was funded in part by the Australian NHMRC (1062683 to M.P.G. and B.R.G.W. and 1124485 to P.G.B. and M.P.G.), the Australian Research Council (140100594 Future Fellowship to M.P.G.); the Fonds de recherche du Quebec-Sante (35071 FRSQ Fellowship to G.P.), and the Victorian Government's Operational Infrastructure Support Program.