Role of diverse NS1 influenza segments in the infection of human bronchial epithelial cells
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PROVIDER: PRJNA762860 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptome comparison of influenza infection with diverse NS1 sequences with a common H5N1 background.
2021-11-22 | GSE184017 | GEO
Project description:Influenza A virus (IAV) is an important human respiratory pathogen that causes significant seasonal epidemics and potential devastating pandemics. As part of its life cycle, IAV encodes the multifunctional protein NS1, that, among many roles, prevents immune detection and limits interferon (IFN) production. As different host immune pathways exert different selective pressures against IAV as replication progresses, we expect a prioritization in the host immune antagonism by NS1. In this work, we profiled bulk transcriptomic differences in a primary bronchial epithelial cell model facing IAV infections at distinct NS1 levels. We further demonstrated that the intracellular NS1 levels in-part shapes the host response heterogeneity at single cell level. We found that modulation of NS1 levels reveal a ranking in its inhibitory roles: modest NS1 expression is sufficient to inhibit immune detection, and thus the expression of pro-inflammatory cytokines (including IFNs), but higher levels are required to inhibit IFN signaling and ISG expression. Lastly, inhibition of chaperones related to the unfolded protein response requires the highest amount of NS1, often associated with later stages of viral replication. This work demystifies some of the multiple functions ascribed to IAV NS1, highlighting the prioritization of NS1 in antagonizing the different pathways involved in the host response to IAV infection.
2023-09-25 | GSE243730 | GEO
Project description:We defined the major transcriptional responses in primary human bronchial epithelial cells (HBECs) after either infection with influenza or treatment with relevant ligands. We used four different strategies, each highlighting distinct aspects of the response. (1) cells were infected with the wild-type PR8 influenza virus that can mount a complete replicative cycle. (2) cells were transfected with viral RNA (âvRNAâ) isolated from influenza particles. This does not result in the production of viral proteins or particles and identifies the effect of RNA-sensing pathways (e.g., RIG-I.). (3) Cells were treated with interferon beta (IFNb), to distinguish the portion of the response which is mediated through Type I IFNs. (4) Cells were infected with a PR8 virus lacking the NS1 gene (âDNS1â). The NS1 protein normally inhibits vRNA- or IFNb-induced pathways, and its deletion can reveal an expanded response to infection. HBECs were stimulated with a 15 minute pulse of 1000U/ml IFNÃ (PBL, Piscataway, NJ), 100ng/ml vRNA (purified directly from PR8 virus) with LTX transfection reagent (Invitrogen; Carlsbad, California), wild type H1N1 influenza (A/PR/8/34) or ?NS1 virus (PR8 with a deleted NS1 gene, gift from Dr. Garcia-Sastre). Viruses were used at a multiplicity of infection (moi) of 5. Control samples were incubated with media or LTX under the same conditions. Cells were washed, supplemented with warm media and harvested at 11 timepoints (0, .25, .5, 1, 1.5, 2, 4, 6, 8, 12, and 18 hours post-treatment). HBECs were seeded in 6 well plates at a concentration of 250,000/well 18 hours prior to stimultaion. Cells were stimulated with a 15 minute pulse of IFNb, vRNA, infected with PR8 influenza or NS1 deleted influenza, or mock treated
2010-04-13 | E-GEOD-19392 | biostudies-arrayexpress
Project description:We defined the major transcriptional responses in primary human bronchial epithelial cells (HBECs) after either infection with influenza or treatment with relevant ligands. We used four different strategies, each highlighting distinct aspects of the response. (1) cells were infected with the wild-type PR8 influenza virus that can mount a complete replicative cycle. (2) cells were transfected with viral RNA (‘vRNA’) isolated from influenza particles. This does not result in the production of viral proteins or particles and identifies the effect of RNA-sensing pathways (e.g., RIG-I.). (3) Cells were treated with interferon beta (IFNb), to distinguish the portion of the response which is mediated through Type I IFNs. (4) Cells were infected with a PR8 virus lacking the NS1 gene (‘DNS1’). The NS1 protein normally inhibits vRNA- or IFNb-induced pathways, and its deletion can reveal an expanded response to infection.
2010-03-30 | GSE19392 | GEO
Project description:Influenza A virus (IAV), one of the most prevalent respiratory diseases, causes pandemics around the world. The multifunctional non-structural protein 1 (NS1) of IAV is a viral antagonist that suppresses host antiviral response. However, the mechanism by which NS1 modulates the RNA interference (RNAi) pathway remains unclear. Here, we identified interactions between NS1 proteins of Influenza A/PR8/34 (H1N1; IAV-PR8) and Influenza A/WSN/1/33 (H1N1; IAV-WSN) and Dicer’s cofactor TAR-RNA binding protein (TRBP). We found that the N-terminal RNA binding domain (RBD) of NS1 and the first two domains of TRBP protein mediated this interaction. Furthermore, two amino acid residues (Arg at position 38 and Lys at position 41) in NS1 were essential for the interaction. We generated TRBP knockout cells and found that NS1 instead of NS1 mutants (two-point mutations within NS1, R38A/K41A) inhibited the process of microRNA (miRNA) maturation by binding with TRBP. PR8-infected cells showed masking of short hairpin RNA (shRNA)-mediated RNAi, which was not observed after mutant virus-containing NS1 mutation (R38A/K41A, termed PR8/3841) infection. Moreover, abundant viral small interfering RNAs (vsiRNAs) were detected in vitro and in vivo upon PR8/3841 infection. We identify, for the first time, the interaction between NS1 and TRBP that affects host RNAi machinery.
2022-04-15 | GSE189776 | GEO
Project description:The influenza virus is opportunistic by nature and is capable of subverting cellular signalling pathways for the benefit of viral replication. The function of non-structural protein 1 (NS1) as a core component for the influenza virus to interfere with host antiviral activity has been well cited in literature. However, the mechanism as to how NS1 is capble of subverting the host's innate immune system is unknown. NS1 has a unique capability to migrate between both the cytoplasm and nucleus of infected cells. To assess if NS1 interference operates a stratagy pertaining to a mechanism involved with nuclear-located signalling processes we designed two mutant virsus; WSNdelNS1 which encodes a deletion to prevent complete NS1 expression and WSN3M which encodes a NS1-variant that is defective in NS1 nuclear-translocation, thus preventing NS1 from entering the nuclus of infected cells.
2020-08-12 | GSE156060 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE39199: Gene Expression Response to Interferon Treatment at 12h and 24 in A549 cells GSE39200: The NS1 protein of influenza A virus suppresses interferon-regulated activation of antigen-presentation and immune-proteasome pathways Refer to individual Series
2012-07-09 | E-GEOD-39202 | biostudies-arrayexpress
Project description:Influenza non-structural protein 1 (NS1) has been well cited to ellicit an inhibitory effect of immune gene expression thus resulting in the curtailment of efficient antiviral immunity. However the mechanisms and gene networks subjected to this immuno-suppression are unclear. We designed an RNA-Seq study to explore this viral trait and characterize the induced gene expression in response to wildtype (native) Influenza A infection. We have also developed an Influenza mutant virus that is deficient in its ability to expression NS1 (WSNdelNS1), thus our study incorporates a virus that will enable induced transcriptomic comparison between wildtype and mutant viral infections.
2020-08-13 | GSE156152 | GEO
Project description:The NS1 protein of influenza virus counters host antiviral defences primarily by antagonizing the type I interferon (IFN) response. Both the N-terminal dsRNA-binding domain and the C-terminal effector domain are required for optimal suppression of host responses during infection. To better understand the regulatory role of the NS1 effector domain, we used an NS1-truncated mutant virus derived from human H1N1 influenza isolate A/Texas/36/91 (Tx/91) and assessed global transcriptional profiles from two independent human lung cell-culture models.
2012-07-10 | GSE39200 | GEO
Project description:The interactome of Influenza (A/WSN/33) NS1 protein (WT and D92Y mutant) was identifiedy by AP-MS.
2021-09-07 | PXD018377 | Pride