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Infection of Bronchial Epithelial Cells by the Human Adenoviruses A12, B3, and C2 Differently Regulates the Innate Antiviral Effector APOBEC3B

Noémie Lejeune, Florian Poulain, Kévin Willemart, Zoé Blockx, Sarah Mathieu, Nicolas Gillet

2021Journal of Virology12 citationsDOIOpen Access PDF

Abstract

The APOBEC3 family of cytosine deaminases has important roles in antiviral innate immunity and cancer. Notably, APOBEC3A and APOBEC3B are actively upregulated by several DNA tumor viruses and contribute to transformation by introducing mutations in the cellular genome. Human adenoviruses (HAdVs) are a large family of DNA viruses that cause generally asymptomatic infections in immunocompetent adults. HAdVs encode several oncogenes, and some HAdV strains, like HAdV-A12, induce tumors in hamsters and mice. Here, we show that HAdV infection specifically promotes the expression of the APOBEC3B gene. We report that infection with the A12 strain induces a strong expression of an enzymatically active APOBEC3B protein in bronchial epithelial cells. We provide bioinformatic evidence that HAdVs' genomes and notably the A12 genome are under APOBEC3 selection pressure. Thus, APOBEC3B might contribute to adenoviral restriction, diversification, and oncogenic potential of particular strains.

Topics & Concepts

BiologyVirologyCytidine deaminaseEffectorInnate immune systemGenomeGeneDownregulation and upregulationGeneticsImmune systemImmunologyVirus-based gene therapy researchImmunotherapy and Immune ResponsesCAR-T cell therapy research