Cytoplasmic Translocation of Nucleolar Protein NOP53 Promotes Viral Replication by Suppressing Host Defense

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• NOP53 is a nucleolar protein previously shown to translocate to the cytoplasm during viral infections (VSV, HSV-1).
• Cytoplasmic NOP53 interacts with RIG-I, reducing ubiquitination and attenuating type I interferon (IFN-β) production.

Purpose of the Study:

• To investigate the role of NOP53 redistribution in viral replication.
• To explore the function of cytoplasmic NOP53 in modulating antiviral responses.
• To assess the impact of a modified NOP53 protein (N3-T) on viral replication and innate immunity.

Main Methods:

• Studied NOP53 translocation during infection with wild-type and mutant HSV-1 (HSV-1/d120).
• Utilized a NOP53 mutant lacking its nuclear export sequence (NES) to block cytoplasmic translocation.
• Induced NOP53 translocation using poly (I:C) or RIG-I-N.
• Constructed and expressed a NOP53-derived protein (N3-T) with a cell-penetrating peptide.
• Assessed IFN-β and IFN-stimulated gene expression, IRF3 phosphorylation, and viral replication rates.

Main Results:

• NOP53 translocation was not observed with a replication-inadequate HSV-1 mutant (HSV-1/d120).
• Blocking NOP53 cytoplasmic translocation abrogated its support for viral replication.
• Poly (I:C) or RIG-I-N directly induced NOP53 cytoplasmic translocation.
• Recombinant N3-T protein formed trimers, suppressed IFN-β and IFN-stimulated genes, and reduced IRF3 phosphorylation.
• N3-T promoted replication of diverse DNA and RNA viruses (enveloped and non-enveloped).

Conclusions:

• NOP53 redistribution from the nucleolus to the cytoplasm is essential for efficient viral replication.
• Cytoplasmic NOP53 plays a key role in suppressing antiviral immunity by targeting RIG-I.
• The NOP53-derived N3-T protein effectively inhibits antiviral responses and enhances replication of a broad range of viruses.