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Effect of brincidofovir on adenovirus and A549 cells transcriptome profiles

Maud Salmona1, Linda Feghoul2, Séverine Mercier-Delarue2

  • 1Université de Paris, INSERM U976, Insight Team, F-75010, Paris, France; Assistance-Publique des Hôpitaux de Paris, Microbiology Department, Virology Unit, Saint Louis Hospital, F-75010, Paris, France.

Antiviral Research
|August 10, 2020
PubMed
Abstract

Insights

Brincidofovir (BCV) reduces human adenovirus (HAdV) replication and alters viral gene expression. This antiviral treatment also enhances cellular antiviral pathways, offering new strategies for controlling HAdV infections.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Human adenovirus (HAdV) infections pose significant risks, especially in transplant patients, necessitating effective antiviral therapies.
  • Brincidofovir (BCV), a cytidine analog, is an antiviral agent that inhibits HAdV replication.
  • The precise mechanisms by which BCV impacts host cellular antiviral responses remain incompletely understood.

Purpose of the Study:

  • To investigate the effects of Brincidofovir (BCV) on cellular antiviral pathways in the context of Human Adenovirus (HAdV) infection.
  • To analyze the impact of BCV on the transcriptome of both HAdV-infected and non-infected lung epithelial cells.

Main Methods:

  • RNA sequencing (RNAseq) was employed to assess the cellular and viral transcriptome.
  • A549 lung epithelial cells were infected with HAdV C5 and treated with or without BCV for 72 hours.
  • Bioinformatic analysis, including ontologic analysis, was performed on the obtained transcriptomic data.

Main Results:

  • BCV treatment significantly reduced viral transcription in HAdV-infected cells, with notable changes in early (E1A, E4) and late (L1) gene expression.
  • BCV profoundly impacted the host cell transcriptome, affecting pathways like mTOR signaling and Wnt pathways.
  • BCV treatment inhibited the biological function of viral replication and modulated 25 genes involved in inflammation.

Conclusions:

  • Brincidofovir (BCV) demonstrably alters viral gene expression and upregulates cellular antiviral pathways in lung epithelial cells.
  • These findings provide novel insights into targeting cellular pathways for the effective control of Human Adenovirus (HAdV) infections.
Keywords:
A549 cellsAdenovirusBrincidofovirTranscriptome

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