Transcriptomics

Dataset Information

3

The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus


ABSTRACT: We investigated the roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus (DENV). Double-deficient Irf-3-/-7-/- mice infected with the DENV2 strain S221 possessed 1,000-150,000 fold higher levels of viral RNA than wild-type and single-deficient mice 24 hours after infection; however, they remained resistant to lethal infection. IFN-α/β was induced similarly in wild-type and Irf-3-/- mice post DENV infection, whereas in the Irf-7-/- and Irf-3-/-7-/- mice, significantly low levels of IFN-α/β expression was observed within 24 hours post-infection. IFN-stimulated gene (ISG) induction was also delayed in Irf-3-/-7-/- mice relative to wild-type and single-deficient mice. In particular, Cxcl10 and Ifnα2 were rapidly induced independently of both IRF-3 and IRF-7 in the Irf-3-/-7-/- mice with DENV infection. Higher levels of serum IFN-γ, IL-6, CXCL10, IL-8, IL-12 p70, and TNF were also observed in Irf-3-/-7-/- mice 24 hours after infection, at which time point viral titers peaked and started to be cleared. Antibody-mediated blockade experiments revealed that IFN-γ, CXCL10, and CXCR3 function to restrict DENV replication in Irf-3-/-7-/- mice. Additionally, the ISGs Cxcl10, Ifit1, Ifit3, and Mx2 can be induced via an IRF-3- and IRF-7-independent pathway that does not involve IFN-γ signaling for protection against DENV. Collectively, these results demonstrate that IRF-3 and IRF-7 are redundant, albeit IRF-7 plays a more important role than IRF-3 in inducing the initial IFN-α/β response; only the combined actions of IRF-3 and IRF-7 are necessary for efficient control of early DENV infection; and the late, IRF-3- and IRF-7-independent pathway contributes to anti-DENV immunity. To identify the antiviral genes that are controlled by IRF-3 and IRF-7 signaling during DENV infection, we examined a panel of ISG expression in the spleens of wild-type, Irf-3-/-, Irf-7-/- and Irf-3-/-7-/- mice at 12 or 24 hours after DENV infection using a quantitative PCR array kit. The fold changes in expression of 55 genes from infected mice were normalized to that of strain-matched naïve mice.

ORGANISM(S): Mus musculus  

SUBMITTER: Andrew D Luster   Jui Tu  Hui-Wen Chen  Marisa Sanchez  Kevin King  Sujan Shresta 

PROVIDER: E-GEOD-49871 | ArrayExpress | 2013-08-15

SECONDARY ACCESSION(S): GSE49871PRJNA215223

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications

The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus.

Chen Hui-Wen HW   King Kevin K   Tu Jui J   Sanchez Marisa M   Luster Andrew D AD   Shresta Sujan S  

Journal of immunology (Baltimore, Md. : 1950) 20130916 8


We investigated the roles of IFN regulatory factor (IRF)-3 and IRF-7 in innate antiviral immunity against dengue virus (DENV). Double-deficient Irf-3(-/-)7(-/-) mice infected with the DENV2 strain S221 possessed 1,000-150,000 fold higher levels of viral RNA than wild-type and single-deficient mice 24 h postinfection (hpi); however, they remained resistant to lethal infection. IFN-α/β was induced similarly in wild-type and Irf-3(-/-) mice post-DENV infection, whereas in the Irf-7(-/-) and Irf-3(-  ...[more]

Similar Datasets

| GSE104189 | GEO
| GSE104214 | GEO
2010-08-22 | GSE21018 | GEO
2016-06-01 | E-GEOD-70429 | ArrayExpress
2009-01-14 | E-GEOD-13522 | ArrayExpress
2009-01-02 | GSE13522 | GEO
2015-08-26 | E-GEOD-72342 | ArrayExpress
2008-06-14 | E-GEOD-6092 | ArrayExpress
| GSE48313 | GEO
2017-02-15 | E-MTAB-5445 | ArrayExpress