Effect of brincidofovir on adenovirus and cellular transcriptome profile.

Brincidofovir is a lipidic conjugate of cidofovir, used as a compassionate treatment for severe human adenovirus (HAdV) infections. Its mechanism of action is the inhibition of DNA polymerase by DNA elongation termination.To determine whether brincidofovir can act against HAdV infections by other mechanisms, we analyzed the impact of brincidofovir in HAdV infected and non-infected lung epithelial cells. We assessed the cellular and viral transcriptome of A549 cells infected or not with HAdV C5 and treated or not with brincidofovir by RNAseq after 72 hours. Brincidofvir treatment of HAdV infected cells resulted in a profound decrease of viral transcription associated with a relative overexpression of the early genes E1A and E4 and of the late gene L1. Brincidofovir had also a profound impact on A549 cells expression. Ontologic analysis revealed an effect of brincidofovir on several pathways known to interact with adenovirus replication as mTor signalling and Wnt pathways. A549 cells treated with brincidofovir demonstrated a significant inhibition of the biological function "viral replication" including 25 dysregulated genes involved in inflammation pathways. Brincidofovir presents antiviral properties mediated by the regulation of cellular signalling pathways involved in viral replication. Further research is needed to better understand the cellular interactome of brincidofovir and its importance in the treatment of viral infections.