Virus-induced APOBEC3 transmutagenesis in bladder cancer initiation.

ABSTRACT: Carcinogenesis in human urothelium is driven by a high burden of mutations caused by the antiviral "APOBEC3" (apolipoprotein B mRNA editing enzyme, catalytic subunit-like 3) cytosine deaminase enzymes; however, there is no established viral etiology. BK polyomavirus (BKPyV) is a ubiquitous childhood infection that persists in the kidney during adulthood and is frequently detected in urine. Chronic BKPyV infections of normal human urothelium induced an innate response, including apical extrusion of infected cells. Local paracrine interferon signaling induced APOBEC3 expression in both infected and juxtaposed bystander cells, leading to acquisition of hallmark APOBEC3-mediated mutational signatures that recapitulated the variation in mutational character found in patients with muscle-invasiv

SUBMITTER: Hatton GH 

PROVIDER: S-EPMC12674112 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature