Dual roles for the ER membrane protein complex in flavivirus infection

viral entry and protein biogenesis

Nicholas J. Barrows, Yesseinia Anglero-Rodriguez, Byungil Kim, Sharon F. Jamison, Caroline Le Sommer, Charles E. McGee, James L. Pearson, George Dimopoulos, Manuel Ascano, Shelton Bradrick, Mariano Garcia-Blanco

Research output: Contribution to journalArticle

Abstract

Hundreds of cellular host factors are required to support dengue virus infection, but their identity and roles are incompletely characterized. Here, we identify human host dependency factors required for efficient dengue virus-2 (DENV2) infection of human cells. We focused on two, TTC35 and TMEM111, which we previously demonstrated to be required for yellow fever virus (YFV) infection and others subsequently showed were also required by other flaviviruses. These proteins are components of the human endoplasmic reticulum membrane protein complex (EMC), which has roles in ER-associated protein biogenesis and lipid metabolism. We report that DENV, YFV and Zika virus (ZIKV) infections were strikingly inhibited, while West Nile virus infection was unchanged, in cells that lack EMC subunit 4. Furthermore, targeted depletion of EMC subunits in live mosquitoes significantly reduced DENV2 propagation in vivo. Using a novel uncoating assay, which measures interactions between host RNA-binding proteins and incoming viral RNA, we show that EMC is required at or prior to virus uncoating. Importantly, we uncovered a second and important role for the EMC. The complex is required for viral protein accumulation in a cell line harboring a ZIKV replicon, indicating that EMC participates in the complex process of viral protein biogenesis.

Original languageEnglish (US)
Article number9711
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Flavivirus Infections
Viral Proteins
Virus Diseases
Dengue Virus
Membrane Proteins
Yellow fever virus
Virus Uncoating
Flavivirus
West Nile virus
Replicon
RNA-Binding Proteins
Viral RNA
Culicidae
Lipid Metabolism
Endoplasmic Reticulum
Proteins
Cell Line

ASJC Scopus subject areas

  • General

Cite this

Dual roles for the ER membrane protein complex in flavivirus infection : viral entry and protein biogenesis. / Barrows, Nicholas J.; Anglero-Rodriguez, Yesseinia; Kim, Byungil; Jamison, Sharon F.; Le Sommer, Caroline; McGee, Charles E.; Pearson, James L.; Dimopoulos, George; Ascano, Manuel; Bradrick, Shelton; Garcia-Blanco, Mariano.

In: Scientific reports, Vol. 9, No. 1, 9711, 01.12.2019.

Research output: Contribution to journalArticle

Barrows, NJ, Anglero-Rodriguez, Y, Kim, B, Jamison, SF, Le Sommer, C, McGee, CE, Pearson, JL, Dimopoulos, G, Ascano, M, Bradrick, S & Garcia-Blanco, M 2019, 'Dual roles for the ER membrane protein complex in flavivirus infection: viral entry and protein biogenesis', Scientific reports, vol. 9, no. 1, 9711. https://doi.org/10.1038/s41598-019-45910-9
Barrows, Nicholas J. ; Anglero-Rodriguez, Yesseinia ; Kim, Byungil ; Jamison, Sharon F. ; Le Sommer, Caroline ; McGee, Charles E. ; Pearson, James L. ; Dimopoulos, George ; Ascano, Manuel ; Bradrick, Shelton ; Garcia-Blanco, Mariano. / Dual roles for the ER membrane protein complex in flavivirus infection : viral entry and protein biogenesis. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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