IFN-kappa Suppresses the Replication of Influenza A Virus through IFNAR-MAPK-Fos-CHD6 Axis
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ABSTRACT:
PROVIDER: PRJNA598132 | ENA |
REPOSITORIES: ENA
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Project description:Type I interferon (IFN) is the first line of defense against virus infection. By using both in vivo and in vitro influenza infection models, we found that type I IFN-κ, limited the replication of influenza viruses by stimulating a IFNAR-MAPK-cFos-CHD6 axis. Similarly, Zika virus (ZIKV) was also highly sensitive to IFN-κ-mediated suppression. With an IAV infected mouse model, we found that IFN-κ was the earliest responding type I interferon among all known members in mice after H9N2 infection, a low-pathogenic Avian Influenza, whereas this early induction did not occur upon highly pathogenic H7N9 infection. IFN-κ can efficiently contain both low- and high-pathogenic influenza replication in cultured human lung cells, and CHD6 was the major effector responsive molecule for IFN-κ, but not for IFN-α/β. Furthermore, we discovered that both IFNAR1 and IFNAR2 subunits of type I interferon receptor and their downstream axis of p38-cFos are engaged in IFN-κ signaling cascade to acti vate CHD6, which didn`t require STAT1 activity. In addition, we showed that the pre-treatment with IFN-κ before IAV challenge protected mice from high mortality. Altogether, our study identified an IFN-κ-specific pathway that suppressed influenza A virus in vitro and in vivo. Thus, IFN-κ may have potential as a new prevention and treatment agents against emerging viruses
2020-04-09 | GSE142708 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-04-09 | GSE142709 | GEO
Project description:Type I interferon (IFN) is the first line of defense against virus infection. By using both in vivo and in vitro influenza infection models, we found that type I IFN-κ, limited the replication of influenza viruses by stimulating a IFNAR-MAPK-cFos-CHD6 axis. Similarly, Zika virus (ZIKV) was also highly sensitive to IFN-κ-mediated suppression. With an IAV infected mouse model, we found that IFN-κ was the earliest responding type I interferon among all known members in mice after H9N2 infection, a low-pathogenic Avian Influenza, whereas this early induction did not occur upon highly pathogenic H7N9 infection. IFN-κ can efficiently contain both low- and high-pathogenic influenza replication in cultured human lung cells, and CHD6 was the major effector responsive molecule for IFN-κ, but not for IFN-α/β. Furthermore, we discovered that both IFNAR1 and IFNAR2 subunits of type I interferon receptor and their downstream axis of p38-cFos are engaged in IFN-κ signaling cascade to acti vate CHD6, which didn`t require STAT1 activity. In addition, we showed that the pre-treatment with IFN-κ before IAV challenge protected mice from high mortality. Altogether, our study identified an IFN-κ-specific pathway that suppressed influenza A virus in vitro and in vivo. Thus, IFN-κ may have potential as a new prevention and treatment agents against emerging viruses
2020-04-09 | GSE142707 | GEO
Project description:Lung cancer is the main cause of cancer-related death in men and women all over the world. Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, with the overall 5-year survival rate is less than 20% . We found the mRNA expression of c-Fos in LUAD clinical samples was decreased significantly compared to adjacent normal control. Overexpression of c-Fos inhibited LUAD cell proliferation, colony formation, and induced cell apoptosis while c-Fos knockdown promoted cell proliferation, colony formation, and suppressed cell apoptosis. Cell cycle showed little difference after c-Fos knockdown but overexpression of c-Fos increased the distribution of G1 phase when decreased G2 phase cells. Knockdown of c-Fos reduced the sensitivity of LUAD cells to cisplatin but overexpression of c-Fos increased the efficacy of cisplatin both in vitro and in vivo. MAPK signaling pathway was enriched after c-Fos was overexpressed in LUAD cells. The expression of c-Jun, c-Myc and DUSP1 was greatly inhibited after c-Fos overexpression but incresed after c-Fos knockdown, which suggests c-Fos regulated MAPK signaling pathway in LUAD. Furthermore, c-Fos was shown to interact with c-Jun and overexpression of c-Jun partially recovered the expression of c-Jun, c-Myc and DUSP1 caused by c-Fos overexpression. Cell proliferation was also rescued when apoptosis was decreased followed by c-Jun overexpression. In contrast, knockdown of c-Jun inhibited cell proliferation and promoted cell apoptosis in LUAD cells when reduced the level of c-Jun, c-Myc and DUSP1. In summary, c-Fos inhibits cell proliferation, promotes apoptosis and increses cisplatin-sensitivity of lung adenocarcinoma cells via regulating MAPK signaling by interacting with c-Jun in certain LUADs.
2023-09-20 | GSE213590 | GEO
Project description:In this study we used CRISPR/Cas9 to generate KO clones of the HEK-RAF-ER cell line that lack expression of EGR1, FOS and profiled the transcriptome after inducing RAF/MAPK signaling.
2024-01-13 | GSE250532 | GEO
Project description:Purpose: While type I interferons (IFN) are important for control of viral replication, we see that, upon infection of Ifnar-/- females were crossed to Ifnar+/- males with ZIKV, only Ifnar+/- fetuses are resorbed or develop severe growth restriction. To identify how IFN may be altering placenta development, we performed RNAsequencing on infected and uninfected Ifnar-/- and Ifnar+/- placentas. Methods: Ifnar-/- females were crossed to Ifnar+/- males and infected intravaginally with Cambodian ZIKV at E5.5. Placentas were harvested from infected and uninfected pregnant dams at E10.5. Results/ Conclusions: Comparison of ZIKV-infected Ifnar-/- and Ifnar+/- shows an elevated interferon stimulated gene (ISG) signature in Ifnar+/- placentas but does not reveal any underlying developmental defects that may be causing defects in placenta development.
2017-12-31 | GSE98423 | GEO
Project description:HEK293T cells were transfected with plasmids expressing a control siRNA or a siRNA especific for CHD6 protein. 48H post-transfection, total RNA was isolated and used for transcriptome analysis. Four biological replicates carried out by triplicate were used.
2018-01-31 | GSE109848 | GEO
Project description:TRPV4 activation induces TMJ degeneration via p38 MAPK/c-Fos/CXCLs axis
| PRJNA1180614 | ENA
Project description:Purpose: Study of the role of CHD6 linking nucleosome ejection in castration-resistant prostate cancer(CRPC) Method: The expression of CHD6 or E2F1 was silenced by 2 shRNAs (3 replicates) targeted at CHD6 or E2F1 in C4-2 cells, scramble RNA as control. mRNA profiles and genome-wide chromatin-state maps were generated by deep sequencing. CHD6 and IgG ChIP was conducted in C4-2 cells. MNase before and after CHD6-silenced was conducted in C4-2 cells. Results: E2F1 and E2F1 downstream genes were significantly down regulated by CHD6 knockdown. The binding of CHD6 on chromatin is required for nucleosome eviction in transcriptional activation of oncogenic pathways.
2022-10-18 | GSE214212 | GEO