Association between Interferon-Inducible Protein 6 (<i>IFI6</i>) Polymorphisms and Hepatitis B Virus Clearance

Park, Geun-Hee; Kim, Kyoung-Yeon; Cho, Sung Won; Cheong, Jae Youn; Yu, Gyeong Im; Shin, Dong Hoon; Kwack, Kyu Bum

doi:10.5808/gi.2013.11.1.15

Cited by 19 publications

(15 citation statements)

References 48 publications

(40 reference statements)

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“…Additionally, the Janus tyrosine kinase (JAK)/ STAT signal transduction pathway regulates IFI6, which is a mitochondria-targeted protein that blocks the release of cytochrome c from mitochondria, and thus delays programmed cell death (apoptosis) that is initiated and signaled by the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/ caspase-8 pathway [ 13 , 14 ]. IFI6 is thus widely considered a pro-survival factor [ 15 ]. Although the functional role of IFI6 in the immune system is quite well known, its antiviral effects are poorly understood [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

IFI6 Inhibits Apoptosis via Mitochondrial-Dependent Pathway in Dengue Virus 2 Infected Vascular Endothelial Cells

Zhang

et al. 2015

PLoS ONE

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Dengue hemorrhagic fever (DHF)/Dengue shock syndrome (DSS) is a fatal infectious disease that demands an effective treatment. Interferon (IFN)-stimulated genes (ISGs) induced by dengue virus (DENV) exert antiviral effects. Among ISGs, IFN-α inducible gene 6 (IFI6) was increased in DENV infected human umbilical vascular endothelial cells (HUVECs) by microarray analysis in our previous study. However, its function is incompletely understood. In this study, we confirmed that IFI6 was markedly induced in DENV infection of both primary HUVECs and EA.hy926 cell lines. Recombinant EA.hy926 cell lines in which IFI6 was either over-expressed (IFI6+/+) or knocked-down (IFI6-/-) were generated. The activation of caspase-3 and intrinsic apoptosis-related protein caspase-9 were down-regulated in IFI6+/+ but up-regulated in IFI6-/- cells at 24–48 hrs post-infection. After incubation with DENV for 48 hrs, the mitochondrial membrane potential (Δψ(m)) was more stable in IFI6+/+ cells but reduced in IFI6-/- cells, as assayed by fluorescence staining with JC-1. We observed that Bcl-2 expression was increased in IFI6+/+ and decreased in IFI6-/- cells. By contrast, Bax expression was decreased in IFI6+/+ and increased in IFI6-/- cells. It is presumed that the anti-apoptotic function of IFI6 is expressed by regulating the rheostatic balance between bcl-2/bax expression and inhibition of Δψ(m) depolarization during DENV infection of vascular endothelial cells(VECs). In addition, the pro-apoptotic protein X-linked Inhibitor of Apoptosis (XIAP)-Associated Factor 1(XAF1) expression had been reported to be up-regulated and led to the induction of apoptosis in DENV2-infected VECs,but the relationship between XAF1 and IFI6 dengue virus-induced apoptosis in VECs warrants further study.

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Section: Introductionmentioning

confidence: 99%

IFI6 Inhibits Apoptosis via Mitochondrial-Dependent Pathway in Dengue Virus 2 Infected Vascular Endothelial Cells

Zhang

et al. 2015

PLoS ONE

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“…1a). For further evaluation, we selected 21 ISGs that caused a statistically significant reduction in virusdriven luciferase expression levels (p-value ≤ 0.05) and one additional ISG, IFI6, (p-value = 0.075) that was previously reported to have antiviral properties 15,20,28 (Fig. 1a; indicated by the black dots).…”

Section: Resultsmentioning

confidence: 99%

“…The RNA genome is tightly encapsidated by NP oligomers and this encapsidated RNA serves as a template for EBOV replication/ transcription 44,45 . NP oligomerization and RNA binding occur simultaneously and synergistically 46 , and these events are mediated by the N-terminal region of NP that includes the N-terminal arm (aa [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] and NP lobes (aa 39-405) including the Cterminal lobe of NP necessary for its interaction with CCDC92 (Fig. 4c).…”

Section: Anti-ebov Activity Of Endogenous Btn3a3 Induced By Ifnγmentioning

confidence: 99%

Identification of interferon-stimulated genes that attenuate Ebola virus infection

et al. 2020

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The West Africa Ebola outbreak was the largest outbreak ever recorded, with over 28,000 reported infections; this devastating epidemic emphasized the need to understand the mechanisms to counteract virus infection. Here, we screen a library of nearly 400 interferonstimulated genes (ISGs) against a biologically contained Ebola virus and identify several ISGs not previously known to affect Ebola virus infection. Overexpression of the top ten ISGs attenuates virus titers by up to 1000-fold. Mechanistic studies demonstrate that three ISGs interfere with virus entry, six affect viral transcription/replication, and two inhibit virion formation and budding. A comprehensive study of one ISG (CCDC92) that shows anti-Ebola activity in our screen reveals that CCDC92 can inhibit viral transcription and the formation of complete virions via an interaction with the viral protein NP. Our findings provide insights into Ebola virus infection that could be exploited for the development of therapeutics against this virus.

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“…[26][27][28] FI44L and IFI6 mediated apoptosis and cell cycle. [29][30] While the down-regulated genes were involved with metabolic enzymes, inflammation, chemokines, cell cycle and receptor related genes ( Table 3).…”

Section: Identifying Degs In the Early Immune Response Of Vaccinementioning

confidence: 99%

Type I interferon related genes are common genes on the early stage after vaccination by meta-analysis of microarray data

Zhang

Shao

et al. 2015

Human Vaccines & Immunotherapeutics

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(2015) Type I interferon related genes are common genes on the early stage after vaccination by meta-analysis of microarray data, Human Vaccines & Immunotherapeutics, 11:3, 739-745, DOI: 10.1080/21645515.2015 The objective of this study was to find common immune mechanism across different kinds of vaccines. A metaanalysis of microarray datasets was performed using publicly available microarray Gene Expression Omnibus (GEO) and Array Express data sets of vaccination records. Seven studies (out of 35) were selected for this meta-analysis. A total of 447 chips (145 pre-vaccination and 302 post-vaccination) were included. Significance analysis of microarrays (SAM) program was used for screening differentially expressed genes (DEGs). Functional pathway enrichment for the DEGs was conducted in DAVID Gene Ontology (GO) database. Twenty DEGs were identified, of which 10 up-regulated genes involved immune response. Six of which were type I interferon (IFN) related genes, including LY6E, MX1, OAS3, IFI44L, IFI6 and IFITM3. Ten down-regulated genes mainly mediated negative regulation of cell proliferation and cell motion. Results of a subgroup analysis showed that although the kinds of genes varied widely between days 3 and 7 post vaccination, the pathways between them are basically the same, such as immune response and response to viruses, etc. For an independent verification of these 6 type I IFN related genes, peripheral blood mononuclear cells (PBMCs) were collected at baseline and day 3 after the vaccination from 8 Enterovirus 71(EV71) vaccinees and were assayed by RT-PCR. Results showed that the 6 DEGs were also upregulated in EV71 vaccinees. In summary, meta-analysis methods were used to explore the immune mechanism of vaccines and results indicated that the type I IFN related genes and corresponding pathways were common in early immune responses for different kinds of vaccines.

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Association between Interferon-Inducible Protein 6 (IFI6) Polymorphisms and Hepatitis B Virus Clearance

Cited by 19 publications

References 48 publications

IFI6 Inhibits Apoptosis via Mitochondrial-Dependent Pathway in Dengue Virus 2 Infected Vascular Endothelial Cells

IFI6 Inhibits Apoptosis via Mitochondrial-Dependent Pathway in Dengue Virus 2 Infected Vascular Endothelial Cells

Identification of interferon-stimulated genes that attenuate Ebola virus infection

Type I interferon related genes are common genes on the early stage after vaccination by meta-analysis of microarray data

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