The Golgi associated ERI3 is a Flavivirus host factor

Alex Michael Ward, Meredith E K Calvert, Leah R. Read, Seokyoung Kang, Brandt E. Levitt, George Dimopoulos, Shelton Bradrick, Jayantha Gunaratne, Mariano Garcia-Blanco

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Dengue virus (DENV) is a mosquito-borne Flavivirus classified into four serotypes (DENV-1-4) that causes Dengue fever (DF), Dengue hemorrhagic Fever (DHF) or Dengue shock syndrome (DSS). An estimated 390 million people are at risk for infection with DENV and there are no effective vaccines or therapeutics. We utilized RNA chromatography coupled with quantitative mass spectrometry (qMS) to identify host RNA binding proteins (RBPs) that interact with DENV-2 RNA. We identified ERI3 (also PRNPIP and PINT1), a putative 3′-5′ RNA exonuclease, which preferentially associates with DENV-2 genomic RNA via interactions with dumbbell structures in the 3′ UTR. ERI3 is required for accumulation of DENV-2 genomic RNA and production of infectious particles. Furthermore, the mosquito homologue of ERI3 is required for DENV-2 replication in adult Aedes aegypti mosquitos implying that the requirement for ERI3 is conserved in both DENV hosts. In human cells ERI3 localizes to the Golgi in uninfected cells, but relocalizes near sites of DENV-2 replication in infected cells. ERI3 is not required for maintaining DENV-2 RNA stability or translation of the viral polyprotein, but is required for viral RNA synthesis. Our results define a specific role for ERI3 and highlight the importance of Golgi proteins in DENV-2 replication.

Original languageEnglish (US)
Article number34379
JournalScientific Reports
Volume6
DOIs
StatePublished - Sep 29 2016

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    Ward, A. M., Calvert, M. E. K., Read, L. R., Kang, S., Levitt, B. E., Dimopoulos, G., Bradrick, S., Gunaratne, J., & Garcia-Blanco, M. (2016). The Golgi associated ERI3 is a Flavivirus host factor. Scientific Reports, 6, [34379]. https://doi.org/10.1038/srep34379