Staufen1 interacts with multiple components of the ebola virus ribonucleoprotein and enhances viral RNA synthesis

Jingru Fang, Colette Pietzsch, Palaniappan Ramanathan, Rodrigo I. Santos, Philipp A. Ilinykh, Mariano Garcia-Blanco, Alexander Bukreyev, Shelton Bradrick

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Ebola virus (EBOV) genome and mRNAs contain long, structured regions that could hijack host RNA-binding proteins to facilitate infection. We performed RNA affinity chromatography coupled with mass spectrometry to identify host proteins that bind to EBOV RNAs and identified four high-confidence proviral host factors, including Staufen1 (STAU1), which specifically binds both 3' and 5' extracis-tronic regions of the EBOV genome. We confirmed that EBOV infection rate and production of infectious particles were significantly reduced in STAU1-depleted cells. STAU1 was recruited to sites of EBOV RNA synthesis upon infection and enhanced viral RNA synthesis. Furthermore, STAU1 interacts with EBOV nucleoprotein (NP), virion protein 30 (VP30), and VP35; the latter two bridge the viral polymerase to the NP-coated genome, forming the viral ribonucleoprotein (RNP) complex. Our data indicate that STAU1 plays a critical role in EBOV replication by coordinating interactions between the viral genome and RNA synthesis machinery. IMPORTANCE Ebola virus (EBOV) is a negative-strand RNA virus with significant public health importance. Currently, no therapeutics are available for Ebola, which imposes an urgent need for a better understanding of EBOV biology. Here we dissected the virus-host interplay between EBOV and host RNA-binding proteins. We identified novel EBOV host factors, including Staufen1, which interacts with multiple viral factors and is required for efficient viral RNA synthesis.

Original languageEnglish (US)
Article numbere01771-18
JournalmBio
Volume9
Issue number5
DOIs
StatePublished - Sep 1 2018

Fingerprint

Ebolavirus
Ribonucleoproteins
Viral RNA
Nucleoproteins
RNA-Binding Proteins
Viral Genome
RNA
Ebola Hemorrhagic Fever
Genome
RNA Viruses
Virus Replication
Infection
Affinity Chromatography
Virion
Mass Spectrometry
Proteins
Public Health

Keywords

  • Ebola virus
  • RNA binding proteins
  • RNA replication
  • Virus-host interactions

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Fang, J., Pietzsch, C., Ramanathan, P., Santos, R. I., Ilinykh, P. A., Garcia-Blanco, M., ... Bradrick, S. (2018). Staufen1 interacts with multiple components of the ebola virus ribonucleoprotein and enhances viral RNA synthesis. mBio, 9(5), [e01771-18]. https://doi.org/10.1128/mBio.01771-18

Staufen1 interacts with multiple components of the ebola virus ribonucleoprotein and enhances viral RNA synthesis. / Fang, Jingru; Pietzsch, Colette; Ramanathan, Palaniappan; Santos, Rodrigo I.; Ilinykh, Philipp A.; Garcia-Blanco, Mariano; Bukreyev, Alexander; Bradrick, Shelton.

In: mBio, Vol. 9, No. 5, e01771-18, 01.09.2018.

Research output: Contribution to journalArticle

Fang, Jingru ; Pietzsch, Colette ; Ramanathan, Palaniappan ; Santos, Rodrigo I. ; Ilinykh, Philipp A. ; Garcia-Blanco, Mariano ; Bukreyev, Alexander ; Bradrick, Shelton. / Staufen1 interacts with multiple components of the ebola virus ribonucleoprotein and enhances viral RNA synthesis. In: mBio. 2018 ; Vol. 9, No. 5.
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