Dissecting Isoform-Specific Functions of PML in Innate Antiviral Immunity Using a Murine Polyomavirus Model

Abstract

The promyelocytic leukemia (PML/TRIM19) protein, a member of the TRIM family, serves as the main scaffold component of PML nuclear bodies (PML NBs), dynamic, multiprotein organelles involved in diverse cellular processes including apoptosis, cell cycle regulation, and the DNA damage response. Moreover, PML NBs act as key antiviral factors, contributing to both intrinsic viral restriction and modulation of type I interferon (IFN-I) mediated innate immune signaling. However, the mechanisms by which PML influences IFN responses remain poorly understood. Recent evidence suggests that PML isoforms shape not only the structure but also the function of PML NBs. Yet, current studies are limited by interspecies models combining human PML isoforms with Pml-knockout mouse embryonic fibroblasts (MEFs).