Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA215223 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2013-08-15 | E-GEOD-49871 | biostudies-arrayexpress
Project description: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.
2013-08-15 | GSE49871 | GEO
Project description:Interferon-regulatory factors (IRFs) are a family of transcription factors (TFs) that play critical roles in translating viral recognition into antiviral responses, including type I IFN production. Dengue virus (DENV) and other clinically important flaviviruses are controlled by functional type I interferon (IFN) responses. Using an experimental model of DENV infection that recapitulates key aspects of the human disease in mice, we demonstrate that while mice lacking the type I IFN receptor (Ifnar1-/-) succumb to DENV infection, mice that are deficient in IRF-3, IRF-5, and IRF-7 – the three transcription factors thought to regulate type I IFN production – survive DENV challenge. Genome-wide RNA-seq analysis of WT, Irf3(-/-)×Irf7(-/-) (DKO), Irf3-/-xIrf5-/-xIrf7-/- (TKO), and Ifnar1-/- (AB6) splenocytes identified minimal type I IFN production but a robust type II IFN (IFN-γ) response in DKO and TKO mice later shown to be dependent on IRF-1. These results reveal a key role for IRF-1 in antiviral defense by activating both type I and II IFN responses during DENV infection.
2017-11-07 | GSE104189 | GEO
Project description:Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV can be sensed by host innate immunity to induce expression of interferons (IFNs) and a number of antiviral effectors. HCV-encoded NS3/4 serine protease can subvert host innate immune responses by cleaving MAVS, a critical adaptor protein in the RLR-mediated IFN signaling. To study innate immunity in the context of HCV infection, we constructed Huh7-MAVSR cells which express a mutant MAVS resistant to NS3/4A cleavage. HCV infection induces robust IFN response in Huh7-MAVSR cells, providing a cellular system to study antiviral innate immune response against HCV infection. To analyze host innate antiviral effectors against HCV infection, we performed an mRNA microarray analysis in the HCV-infected Huh7-MAVSR cells.
2018-02-08 | GSE110312 | GEO
Project description:Peroxisomes are signaling patforms for antiviral innate immunity
| PRJNA126311 | ENA
Project description:Analysis of the host response to dengue virus at gene expression level. The hypothesis tested in the present study was that dengue virus triggers and regulate different pathaway with different kinetics controlling the antiviral, the inflammatory and the apoptotic response in primary human DC. Results provide important information of the response to DC to dengue virus showing that antioxidant genes are early stimulated after denv infection reflecting an early production of reactive oxygen species. Interestingely, we demonstrated that ROS production and antiviral and apoptotic responses intersect since chemical inhibition of ROS impairs antiviral and apoptotic responses in these cells. Total RNA obtained from in vitro dengue infected primary human dendritic cells at 0, 6, 12, 18, 24 hours compared to uninfected cells at time 0
2014-12-18 | E-GEOD-58278 | biostudies-arrayexpress
Project description:West Nile virus (WNV) is an emerging mosquito-borne flavivirus, related to dengue virus and Zika virus. To gain insight into host pathways involved in WNV infection, we performed a systematic affinity-tag purification mass spectrometry (AP-MS) study to identify 259 WNV-interacting human proteins. RNAi screening revealed 26 genes that both interact with WNV proteins and influence WNV infection. We found that WNV, dengue and Zika virus capsids interact with a conserved subset of proteins that impact infection. These include the exon-junction complex (EJC) recycling factor, PYM1, which is antiviral against all three viruses. The EJC has roles in nonsense-mediated decay (NMD), and we found that both the EJC and NMD are antiviral. Mechanistically, we found that the EJC protein RBM8A directly binds WNV RNA. To counteract this antiviral defense, flavivirus infection inhibits NMD and the interaction of capsid with PYM1 interferes with EJC protein function and localization. Moreover, depletion of PYM1 attenuates RBM8A binding to viral RNA, suggesting that WNV sequesters PYM1 to protect viral RNA from decay. Together, these data suggest a complex interplay between the virus and host in regulating NMD and the EJC complex.
2019-11-14 | PXD011728 | Pride
Project description:TRAIL Is a Novel Antiviral Protein against Dengue Virus
| PRJNA103087 | ENA
Project description:Analysis of the host response to dengue virus at gene expression level. The hypothesis tested in the present study was that dengue virus triggers and regulate different pathaway with different kinetics controlling the antiviral, the inflammatory and the apoptotic response in primary human DC. Results provide important information of the response to DC to dengue virus showing that antioxidant genes are early stimulated after denv infection reflecting an early production of reactive oxygen species. Interestingely, we demonstrated that ROS production and antiviral and apoptotic responses intersect since chemical inhibition of ROS impairs antiviral and apoptotic responses in these cells.
2014-12-18 | GSE58278 | GEO
Project description:Virus-misplaced host protein activates innate immunity
| PRJNA151845 | ENA