Differences in type I interferon signaling antagonism by dengue viruses in human and non-human primate cell lines

PLoS Neglected Tropical Diseases
Freddy A MedinaJorge L Muñoz-Jordán

Abstract

In vitro studies have shown that dengue virus (DENV) can thwart the actions of interferon (IFN)-α/β and prevent the development of an antiviral state in infected cells. Clinical studies looking at gene expression in patients with severe dengue show a reduced expression of interferon stimulated genes compared to patients with dengue fever. Interestingly, there are conflicting reports as to the ability of DENV or other flaviviruses to inhibit IFN-α/β signaling. In order to determine the relative inhibition of IFN-α/β signaling by DENVs, a method combining flow cytometry and a four-parameter logistic regression model was established. A representative isolate from DENV-1, -3 and -4 and seventeen representative isolates encompassing all DENV-2 genotypes were evaluated. All of the DENVs evaluated in this study were capable of inhibiting IFN-α/β signaling. Most of the strains were able to inhibit IFN-α/β to a degree similar to DENV strain 16681; however, DENV-2 sylvatic strains demonstrated an increased inhibition of phosphorylated signal transducer and activator of transcription (pSTAT1). Surprisingly, we were unable to observe inhibition of pSTAT1 by DENV-2 sylvatic strains or the Asian strain 16681 in non-human primate (NHP) cell l...Continue Reading

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Citations

Feb 17, 2017·Cellular Microbiology·Nilanka PereraNicole Zitzmann
Nov 18, 2016·PLoS Computational Biology·Rotem Ben-ShacharKatia Koelle
Jun 20, 2019·PLoS Neglected Tropical Diseases·Carolina Torturella RathUlisses Gazos Lopes
Jul 31, 2018·The Journal of Infectious Diseases·Freddy A MedinaJorge L Muñoz-Jordán

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Methods Mentioned

BETA
flow cytometry
fluorescence-activated cell sorting
ELISA
electrophoresis

Software Mentioned

Digimizer®
FlowJo
Mega
GraphPad
BD Cell Quest
GraphPad InStat
MedCalc

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