Protective Roles of Interferon-Induced Protein with Tetratricopeptide Repeats 3 (IFIT3) in Dengue Virus Infection of Human Lung Epithelial Cells
Open Access
- 4 November 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (11), e79518
- https://doi.org/10.1371/journal.pone.0079518
Abstract
Interferons (IFNs) are critical cytokines that regulate immune response against virus infections. Dengue virus (DV) infections are a major public health concern worldwide, and especially in Asia. In the present study, we investigated the effects and mechanisms of action of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in human lung epithelial cells. The results demonstrated that DV infection induced expression of several IFITs, including IFIT1, IFIT2, IFIT3, and IFIT5 in A549 cells. Induction of IFIT3 by DV infection was also observed in human dendritic cells. In a knockdown study, we showed that a signal transducer and activator of transcription 2 (STAT2), but not STAT1 or STAT3, regulated DV-induced IFIT3 production. By using several different methods to evaluate cell death, we demonstrated that knockdown of IFIT3 led to cellular apoptosis. Furthermore, knockdown of IFIT3 induced the expression of several apoptotic regulators such as caspase 3, caspase 8, caspase 9, and Bcl-2-associated X protein (BAX). Such apoptotic effects and mechanisms were synergistically enhanced after DV infection. Moreover, under conditions of IFIT3 deficiency, viral production increased, suggesting an anti-viral effect of IFIT3. Interestingly, DV could suppress IFN-α-induced but not IFN-γ-induced IFIT3 expression, a phenomenon similar to the regulation of STATs by DV. In conclusion, this study revealed some mechanisms of IFIT3 induction, and also demonstrated the protective roles of IFIT3 following IFN-α production in DV infection of human lung epithelial cells.Keywords
This publication has 35 references indexed in Scilit:
- A diverse range of gene products are effectors of the type I interferon antiviral responseNature, 2011
- The Interferon Stimulated Gene 54 Promotes ApoptosisJournal of Biological Chemistry, 2011
- TheISG56/IFIT1Gene FamilyJournal of Interferon & Cytokine Research, 2011
- 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family membersNature, 2010
- Identification of Alpha Interferon-Induced Genes Associated with Antiviral Activity in Daudi Cells and Characterization of IFIT3 as a Novel Antiviral GeneJournal of Virology, 2010
- The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue VirusCell, 2009
- ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral responseProceedings of the National Academy of Sciences, 2009
- Interferon-inducible antiviral effectorsNature Reviews Immunology, 2008
- IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis virusesProceedings of the National Academy of Sciences, 2007
- RIG-G as a key mediator of the antiproliferative activity of interferon-related pathways through enhancing p21 and p27 proteinsProceedings of the National Academy of Sciences, 2006