Nucleophosmin (NPM1)/B23 in the Proteome of Human Astrocytic Cells Restricts Chikungunya Virus Replication

Rachy Abraham, Sneha Singh, Sreeja R. Nair, Neha Vijay Hulyalkar, Arun Surendran, Abdul Jaleel, Easwaran Sreekumar

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4144-4155
Number of pages12
JournalJournal of proteome research
Volume16
Issue number11
DOIs
StatePublished - Nov 3 2017
Externally publishedYes

Keywords

  • arbovirus
  • astrocytes
  • central nervous system
  • chikungunya
  • label-free proteomics
  • nucleophosmin

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry

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