Identification and characterization of host proteins bound to dengue virus 3' UTR reveal an antiviral role for quaking proteins

Kuo Chieh Liao, Vanessa Chuo, Wy Ching Ng, Suat Peng Neo, Julien Pompon, Jayantha Gunaratne, Eng Eong Ooi, Mariano Garcia-Blanco

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The four dengue viruses (DENV1-4) are rapidly reemerging infectious RNA viruses. These positive-strand viral genomes contain structured 3'' untranslated regions (UTRs) that interact with various host RNA binding proteins (RBPs). These RBPs are functionally important in viral replication, pathogenesis, and defense against host immune mechanisms. Here, we combined RNA chromatography and quantitative mass spectrometry to identify proteins interacting with DENV1-4 3'' UTRs. As expected, RBPs displayed distinct binding specificity. Among them, we focused on quaking (QKI) because of its preference for the DENV4 3'' UTR (DENV-4/SG/06K2270DK1/2005). RNA immunoprecipitation experiments demonstrated that QKI interacted with DENV4 genomes in infected cells. Moreover, QKI depletion enhanced infectious particle production of DENV4. On the contrary, QKI did not interact with DENV2 3'' UTR, and DENV2 replication was not affected consistently by QKI depletion. Next, we mapped the QKI interaction site and identified a QKI response element (QRE) in DENV4 3'' UTR. Interestingly, removal of QRE from DENV4 3'' UTR abolished this interaction and increased DENV4 viral particle production. Introduction of the QRE to DENV2 3'' UTR led to QKI binding and reduced DENV2 infectious particle production. Finally, reporter assays suggest that QKI reduced translation efficiency of viral RNA. Our work describes a novel function of QKI in restricting viral replication.

Original languageEnglish (US)
Pages (from-to)803-814
Number of pages12
JournalRNA
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

Dengue Virus
3' Untranslated Regions
Antiviral Agents
RNA-Binding Proteins
Response Elements
Proteins
RNA
Viral Genome
RNA Viruses
Viral RNA
Immunoprecipitation
Virion
Chromatography
Mass Spectrometry
Genome

Keywords

  • Dengue virus
  • Host factors
  • QKI
  • RNA elements
  • Translation

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Identification and characterization of host proteins bound to dengue virus 3' UTR reveal an antiviral role for quaking proteins. / Liao, Kuo Chieh; Chuo, Vanessa; Ng, Wy Ching; Neo, Suat Peng; Pompon, Julien; Gunaratne, Jayantha; Ooi, Eng Eong; Garcia-Blanco, Mariano.

In: RNA, Vol. 24, No. 6, 01.06.2018, p. 803-814.

Research output: Contribution to journalArticle

Liao, Kuo Chieh ; Chuo, Vanessa ; Ng, Wy Ching ; Neo, Suat Peng ; Pompon, Julien ; Gunaratne, Jayantha ; Ooi, Eng Eong ; Garcia-Blanco, Mariano. / Identification and characterization of host proteins bound to dengue virus 3' UTR reveal an antiviral role for quaking proteins. In: RNA. 2018 ; Vol. 24, No. 6. pp. 803-814.
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