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

Autor: Hwa-Chain Robert Wang, Jian-Yu Chang, Cui-Cui Li, Xiao-Jia Wang, Shichong Han, Hui-Jun Dong, Wen Meng
Rok vydání: 2018
Předmět:
0301 basic medicine
Cytoplasm
viruses
lcsh:QR1-502
Cell-Penetrating Peptides
Herpesvirus 1
Human
medicine.disease_cause
Virus Replication
lcsh:Microbiology
0302 clinical medicine
Interferon
Phosphorylation
IFN-β
Sequence Deletion
Nuclear Proteins
Cell biology
Infectious Diseases
Vesicular stomatitis virus
Host-Pathogen Interactions
DEAD Box Protein 58
cytoplasmic translocation
tat Gene Products
Human Immunodeficiency Virus
medicine.drug
Recombinant Fusion Proteins
Down-Regulation
Biology
Virus
Article
Cell Line
03 medical and health sciences
Virology
medicine
Animals
Humans
Nuclear export signal
Gene
Nuclear Export Signals
Tumor Suppressor Proteins
Interferon-beta
biology.organism_classification
NOP53
recombinant protein
viral replication
030104 developmental biology
Herpes simplex virus
Poly I-C
Viral replication
Interferon Regulatory Factor-3
IRF3
030215 immunology
Zdroj: Viruses
Viruses; Volume 10; Issue 4; Pages: 208
Viruses, Vol 10, Iss 4, p 208 (2018)
ISSN: 1999-4915
Popis: NOP53 is a tumor suppressor protein located in the nucleolus and is translocated to the cytoplasm during infection by vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1), as shown in our previous study. Cytoplasmic NOP53 interacts with the retinoic acid-inducible gene I (RIG-I) to remove its K63-linked ubiquitination, leading to attenuation of type I interferon IFN-β. In the present study, we found no obvious translocation of NOP53 in infection by a mutant virus lacking ICP4 (HSV-1/d120, replication inadequate). Blocking cytoplasmic translocation of NOP53 by the deletion of its nuclear export sequence (NES) abrogated its ability to support viral replication. These results demonstrated that NOP53 redistribution is related to viral replication. It is interesting that treatment with poly (I:C) or RIG-I-N (a constitutively-active variant) directly induced NOP53 cytoplasmic translocation. To better assess the function of cytoplasmic NOP53 in viral replication, the NOP53-derived protein N3-T, which contains a human immunodeficiency virus (HIV)-derived cell-penetrating Tat peptide at the C-terminal region of N3 (residues 330–432), was constructed and expressed. The recombinant N3-T protein formed trimers, attenuated the expression of IFN-β and IFN-stimulated genes, as well as decreased the phosphorylation level of interferon regulatory factor 3 (IRF3). Furthermore, N3-T promoted the efficient replication of enveloped and non-enveloped DNA and RNA viruses belonging to 5 families. Our findings expand the understanding of the mechanism by which viruses utilize the nucleolar protein NOP53 for optimal viral replication.
Databáze: OpenAIRE
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