The human cytomegalovirus IE1 protein antagonizes PML nuclear body-mediated intrinsic immunity via the inhibition of PML de novo SUMOylation

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autor(en): Schilling EM, Scherer M, Reuter N, Schweininger J, Muller Y, Stamminger T
Zeitschrift: Journal of Virology
Verlag: American Society for Microbiology
Jahr der Veröffentlichung: 2017
Band: 91
Heftnummer: 4
ISSN: 1098-5514


Abstract


PML nuclear bodies (NBs) are accumulations of cellular proteins embedded in a scaffold-like structure built by SUMO-modified PML/TRIM19. PML and other NB proteins act as cellular restriction factors against human cytomegalovirus (HCMV); however, this intrinsic defense is counteracted by the immediate early protein 1 (IE1) of HCMV. IE1 directly interacts with the PML coiled-coil domain via its globular core region and disrupts NB foci by inducing a loss of PML SUMOylation. Here, we demonstrate that IE1 acts via abrogating the de novo SUMOylation of PML. In order to overcome reversible SUMOylation dynamics, we made use of a cell-based assay that combines inducible IE1 expression with a SUMO mutant resistant to SUMO proteases. Interestingly, we observed that IE1 expression did not affect preSUMOylated PML; however, it clearly prevented de novo SUMO conjugation. Consistent results were obtained by in vitro SUMOylation assays, demonstrating that IE1 alone is sufficient for this effect. Furthermore, IE1 acts in a selective manner, since K160 was identified as the main target lysine. This is strengthened by the fact that IE1 also prevents AsO-mediated hyperSUMOylation of K160, thereby blocking PML degradation. Since IE1 did not interfere with coiled-coil-mediated PML dimerization, we propose that IE1 affects PML autoSUMOylation either by directly abrogating PML E3 ligase function or by preventing access to SUMO sites. Thus, our data suggest a novel mechanism for how a viral protein counteracts a cellular restriction factor by selectively preventing the de novo SUMOylation at specific lysine residues without affecting global protein SUMOylation.



FAU-Autoren / FAU-Herausgeber

Muller, Yves Prof. Dr.
Lehrstuhl für Biotechnik (Proteinstruktur und -design)
Scherer, Myriam
Professur für Virologie
Schilling, Eva-Maria
Professur für Virologie
Schweininger, Johannes
Sonderforschungsbereich 796 (mit integriertem Graduiertenkolleg) Steuerungsmechanismen mikrobieller Effektoren in Wirtszellen
Stamminger, Thomas Prof. Dr.
Professur für Virologie


Zitierweisen

APA:
Schilling, E.-M., Scherer, M., Reuter, N., Schweininger, J., Muller, Y., & Stamminger, T. (2017). The human cytomegalovirus IE1 protein antagonizes PML nuclear body-mediated intrinsic immunity via the inhibition of PML de novo SUMOylation. Journal of Virology, 91(4). https://dx.doi.org/10.1128/JVI.02049-16

MLA:
Schilling, Eva-Maria, et al. "The human cytomegalovirus IE1 protein antagonizes PML nuclear body-mediated intrinsic immunity via the inhibition of PML de novo SUMOylation." Journal of Virology 91.4 (2017).

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Zuletzt aktualisiert 2018-10-11 um 20:50