The Golgi associated ERI3 is a Flavivirus host factor.
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.
Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore.
Alex Michael
AM
Ward
Bioimaging &Biocomputing Facility, Temasek Lifesciences Laboratory, Singapore.
Meredith E K
ME
Calvert
Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore.
Leah R
LR
Read
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Seokyoung
S
Kang
Center for RNA Biology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
Brandt E
BE
Levitt
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
George
G
Dimopoulos
Center for RNA Biology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.|Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas, USA.
Shelton S
SS
Bradrick
Translational Biomedical Proteomics Laboratory, Institute of Molecular and Cell Biology, Singapore.|Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Jayantha
J
Gunaratne
Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore.|Center for RNA Biology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.|Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas, USA.|Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Mariano A
MA
Garcia-Blanco
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