A UL26-PIAS1 complex antagonizes anti-viral gene expression during Human Cytomegalovirus infection.
PLoS Pathog
; 20(5): e1012058, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38768227
ABSTRACT
Viral disruption of innate immune signaling is a critical determinant of productive infection. The Human Cytomegalovirus (HCMV) UL26 protein prevents anti-viral gene expression during infection, yet the mechanisms involved are unclear. We used TurboID-driven proximity proteomics to identify putative UL26 interacting proteins during infection to address this issue. We find that UL26 forms a complex with several immuno-regulatory proteins, including several STAT family members and various PIAS proteins, a family of E3 SUMO ligases. Our results indicate that UL26 prevents STAT phosphorylation during infection and antagonizes transcriptional activation induced by either interferon α (IFNA) or tumor necrosis factor α (TNFα). Additionally, we find that the inactivation of PIAS1 sensitizes cells to inflammatory stimulation, resulting in an anti-viral transcriptional environment similar to ΔUL26 infection. Further, PIAS1 is important for HCMV cell-to-cell spread, which depends on the presence of UL26, suggesting that the UL26-PIAS1 interaction is vital for modulating intrinsic anti-viral defense.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Virales
/
Infecciones por Citomegalovirus
/
Citomegalovirus
/
Proteínas Inhibidoras de STAT Activados
Límite:
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article