Project description:RNAseq analysis of A549-TRIM28 KO cells that were infected with low pathogenic laboratory strain PR8 (H1N1) Differentially expressed genes in infected vs. non-infected cells Project: A549_TRIM28_KO
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
Project description:Modulating the host response is a promising approach to treating influenza, a virus whose pathogenesis is determined in part by the host response it elicits. Though the pathogenicity of emerging H7N9 influenza virus has been reported in several animal models, these studies have not included a detailed characterization of the host response following infection. To this end, we characterized the transcriptomic response of BALB/c mice infected with H7N9 (A/Anhui/1/2013) virus and compared it to the responses induced by H5N1 (A/Vietnam/1203/2004), H7N7 (A/Netherlands/219/2003) or H1N1 (A/Mexico/4482/2009) viruses. We found that responses to the H7 subtype viruses were intermediate to those elicited by H5N1 and H1N1 early in infection, but that they evolved to resemble the H5N1 response as infection progressed. H5N1, H7N7 and H7N9 viruses were pathogenic in mice, and this pathogenicity correlated with increased cytokine response, decreased lipid metabolism and decreased coagulation signaling. This three-pronged signature has previously been observed in mice infected with pathogenic H1N1 strains such as the 1918 virus, indicating that it may be predictive of pathogenicity across multiple influenza strains.
Project description:Modulating the host response is a promising approach to treating influenza, a virus whose pathogenesis is determined in part by the host response it elicits. Though the pathogenicity of emerging H7N9 influenza virus has been reported in several animal models, these studies have not included a detailed characterization of the host response following infection. To this end, we characterized the transcriptomic response of BALB/c mice infected with H7N9 (A/Anhui/1/2013) virus and compared it to the responses induced by H5N1 (A/Vietnam/1203/2004), H7N7 (A/Netherlands/219/2003) or H1N1 (A/Mexico/4482/2009) viruses. We found that responses to the H7 subtype viruses were intermediate to those elicited by H5N1 and H1N1 early in infection, but that they evolved to resemble the H5N1 response as infection progressed. H5N1, H7N7 and H7N9 viruses were pathogenic in mice, and this pathogenicity correlated with increased cytokine response, decreased lipid metabolism and decreased coagulation signaling. This three-pronged signature has previously been observed in mice infected with pathogenic H1N1 strains such as the 1918 virus, indicating that it may be predictive of pathogenicity across multiple influenza strains. Groups of 6- to 8-week-old BALB/c mice were infected with either A/Anhui/01/2013 (H7N9), A/Netherlands/219/2003 (H7N7), A/Vietnam/1203/2004 (H5N1), or pandemic H1N1 human virus, A/Mexico/4482/2007 (H1N1). Infections were done at 10^5 PFU or time-matched mock infected. Time points were 1, 3 and 5 d.p.i. There were 4-5 infected and 3 mock infected animals/time point. Lung samples were collected for virus load and transcriptional analysis. Weight loss and animal survival were also monitored.
Project description:mRNA-Seq analysis was used to profile the cellular transcriptome of A549 cells at multiple time points in response to infection with influenza H7N9.
Project description:We used the microarray data to analyze host cells response on A549 cells infected with A/Duck/Malaysia/01 (H9N2) The A/Duck/Malaysia/01 (H9N2) infected A549 cells were harvested at 2, 4, 6, 8 and 10 hpi and RNA extraction was performed using standard protocol as described by Affymetrix. The aim of this experiment is to analyze host response to Influenza A/Duck/Malaysia/01 (H9N2) infection.