Nucleophosmin (NPM1)/B23 in the Proteome of Human Astrocytic Cells Restricts Chikungunya Virus Replication
| Autor: | Arun Surendran, Neha Vijay Hulyalkar, Rachy Abraham, Sneha Singh, Abdul Jaleel, E. Sreekumar, Sreeja R. Nair |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteome 030106 microbiology Virus Replication Biochemistry Virus Cell Line 03 medical and health sciences Antigen Humans Nucleophosmin biology virus diseases Nuclear Proteins RNA virus General Chemistry biology.organism_classification Virology 030104 developmental biology Viral replication Cell culture Chaperone (protein) Astrocytes biology.protein Chikungunya Fever Chikungunya virus |
| Zdroj: | Journal of proteome research. 16(11) |
| ISSN: | 1535-3907 |
| Popis: | Chikungunya virus (CHIKV), a positive-stranded RNA virus, can cause neurological complications by infecting the major parenchymal cells of the brain such as neurons and astrocytes. A proteomic analysis of CHIKV-infected human astrocytic cell line U-87 MG revealed tight functional associations among the modulated proteins. The predominant cellular pathways involved were of transcription-translation machinery, cytoskeletol reorganization, apoptosis, ubiquitination, and metabolism. In the proteome, we could also identify a few proteins that are reported to be involved in host-virus interactions. One such protein, Nucleophosmin (NPM1)/B23, a nucleolar protein, showed enhanced cytoplasmic aggregation in CHIKV-infected cells. NPM1 aggregation was predominantly localized in areas wherein CHIKV antigen could be detected. Furthermore, we observed that inhibition of this aggregation using a specific NPM1 oligomerization inhibitor, NSC348884, caused a significant dose-dependent enhancement in virus replication. There was a marked increase in the amount of intracellular viral RNA, and ∼105-fold increase in progeny virions in infected cells. Our proteomic analysis provides a comprehensive spectrum of host proteins modulated in response to CHIKV infection in astrocytic cells. Our results also show that NPM1/B23, a multifunctional chaperone, plays a critical role in restricting CHIKV replication and is a possible target for antiviral strategies. |
| Databáze: | OpenAIRE |
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