Dual signaling via interferon and DNA damage response elicits entrapment by giant PML nuclear bodies
Scherer M, Read C, Neusser G, Kranz C, Kuderna AK, Müller R, Full F, Wörz S, Reichel A, Schilling EM, Walther P, Stamminger T (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 11
Article Number: e73006
DOI: 10.7554/eLife.73006
Abstract
PML nuclear bodies (PML-NBs) are dynamic interchromosomal macromolecular complexes implicated in epigenetic regulation as well as antiviral defense. During herpesvirus infec-tion, PML-NBs induce epigenetic silencing of viral genomes, however, this defense is antagonized by viral regulatory proteins such as IE1 of human cytomegalovirus (HCMV). Here, we show that PML-NBs undergo a drastic rearrangement into highly enlarged PML cages upon infection with IE1-deficient HCMV. Importantly, our results demonstrate that dual signaling by interferon and DNA damage response is required to elicit giant PML-NBs. DNA labeling revealed that invading HCMV genomes are entrapped inside PML-NBs and remain stably associated with PML cages in a transcrip-tionally repressed state. Intriguingly, by correlative light and transmission electron microscopy (EM), we observed that PML cages also entrap newly assembled viral capsids demonstrating a second defense layer in cells with incomplete first-line response. Further characterization by 3D EM showed that hundreds of viral capsids are tightly packed into several layers of fibrous PML. Overall, our data indicate that giant PML-NBs arise via combined interferon and DNA damage signaling which trig-gers entrapment of both nucleic acids and proteinaceous components. This represents a multilay-ered defense strategy to act in a cytoprotective manner and to combat viral infections.
Involved external institutions
Germany (DE)How to cite
APA:
Scherer, M., Read, C., Neusser, G., Kranz, C., Kuderna, A.K., Müller, R.,... Stamminger, T. (2022). Dual signaling via interferon and DNA damage response elicits entrapment by giant PML nuclear bodies. eLife, 11. https://doi.org/10.7554/eLife.73006
MLA:
Scherer, Myriam, et al. "Dual signaling via interferon and DNA damage response elicits entrapment by giant PML nuclear bodies." eLife 11 (2022).
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