Influenza A virus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA561570 | ENA |
REPOSITORIES: ENA
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Project description:Long noncoding RNAs (lncRNAs) participate in regulating many biological processes. However, their roles in influenza A virus (IAV) pathogenicity are largely unknown. Here, we analyzed the expression profile of lncRNAs and mRNAs in the H3N2-infected cells and H7N9-infected cells by high-throughput sequencing
2020-05-13 | GSE135482 | GEO
Project description:Influenza A virus (IAV) is the etiological agent of a highly contagious acute respiratory disease, which causes a considerable socioeconomic burden despite annual vaccination campaigns. Therefore, it is essential to better understand IAV-host cells interaction to help design innovative antiviral therapies. In that regard, recent studies revealed the interplay between metabolic and immune signaling pathways. However, it remains unknown whether IAV alters lung tissues metabolism and what is its potential functional consequence. Using in vitro and in vivo models as well as human respiratory fluids and in-depth metabolomics analysis, we first found that IAV infection alters the glycolysis and mitochondrial oxidative respiration in lung tissues, leading to the accumulation of several immunometabolites in the bronchoalveolar airspaces. We next focused on one mitochondria-derived metabolite, i.e. succinate as its accumulation was found not only in the lungs of IAV-challenged mice but also in the tracheal fluids of IAV-infected patients. Remarkably, we found that succinate exhibits a potent antiviral activity both in vitro and in vivo as it inhibits H1N1 and H3N2 IAV strains and it strongly decreases IAV-triggered inflammatory response. The underlying inhibiting mechanism involves a disruption of IAV replication cycle. Indeed, succinate prevents specifically the nuclear export of the viral nucleoprotein NP, likely due to a specific succinylation at K87 site. Finally, we showed that mice receiving succinate through the intranasal route are more resistant to IAV pneumonia than mock-treated animals. Hence, our study identifies the metabolite succinate as a novel component of the host antiviral arsenal.
2022-03-24 | PXD018419 | Pride
Project description:CRISPR technology offers an entirely new approach to therapeutic development because it can target specific nucleotide sequences with high specificity, however, preclinical animal models are not useful for evaluation of their efficacy and potential off-target effects because of high gene sequence variations between animals and humans. Here, we explored the potential of using the CRISPR effector Cas13 to develop new therapeutic approach for influenza A virus (IAV) infections based on its ability to specifically and robustly cleave single-strand viral RNA using a complementary CRISPR RNA (crRNA). We engineered crRNAs to target highly conserved regions in the IAV genome to create a potential pan-viral treatment strategy. A human lung alveolus chip (Lung Chip) lined by human primary alveolar epithelial cells interfaced with human primary pulmonary microvascular endothelial cells and infected with a pandemic IAV H3N2 strain was used to evaluate the on-target and off-target effects of these antiviral crRNA therapeutics. Our data show that the crRNAs targeting highly conserved regions in the IAV genome potently reduced viral replication in the alveolar airspace in the Lung Chip, and this was accompanied by suppression of the human host inflammatory response as indicated by a significant reduction in cytokine production and recruitment of immune cells. Importantly, only minimal off-target effects were observed based on transcriptomic analyses. As these crRNAs inhibit replication of influenza H1N1 and H3N2 in A549 cells as well as H3N2 in Lung Chips, these findings support use of CRISPR-Cas13 as a potentially viable approach to develop pan-IAV therapeutics or combating future influenza pandemics. The results also demonstrate that human Organ Chips be useful as more clinically relevant preclinical models for testing the efficacy and safety of crRNA therapeutics.
2025-12-06 | GSE272709 | GEO
Project description:Influenza A virus (IAV) is a human respiratory pathogen that causes yearly global epidemics, and sporadic pandemics due to human adaptation of pathogenic strains. Efficient replication of IAV in different species is, in part, dictated by its ability to exploit the genetic environment of the host cell. To investigate IAV tropism in human cells, we evaluated the replication of IAV strains in a diverse subset of epithelial cell lines. HeLa cells were refractory to growth of human H1N1 and H3N2, and low pathogenic avian influenza (LPAIs) viruses. Interestingly, a human isolate of the highly pathogenic avian influenza (HPAI) virus H5N1 successfully propagated in HeLa cells to levels comparable to a human lung cell line. Heterokaryon cells generated by fusion of HeLa and permissive cells supported H1N1 growth, suggesting the absence of a host factor(s) required for replication of H1N1, but not H5N1, in HeLa cells. The absence of this factor(s) was mapped to reduced nuclear import, replication, and translation, and deficient viral budding. Using reassortant H1N1:H5N1 viruses, we found that the combined introduction of nucleoprotein (NP) and hemagglutinin (HA) from H5N1 was necessary and sufficient to enable H1N1 growth. Overall, this study suggests the absence of one or more cellular factors in HeLa cells that results in abortive replication of H1N1, H3N2, and LPAI viruses, but can be circumvented upon introduction of H5N1 NP and HA. Further understanding of the molecular basis of this restriction will provide important insights into virus-host interactions that underlie IAV pathogenesis and tropism.
2019-11-21 | GSE140759 | GEO
Project description:We used RNA sequencing to comprehensively map the expression of coding and non-coding RNAs in primary human alveolar epithelial type II cells (AECIIs), alveolar macrophages (AMs), human lung tissue, and the epithelial cell line A549 during infection with IAV strain H3N2 Panama
2022-12-16 | GSE206606 | GEO
Project description:To study the impact of influenza infection on gene expression changes in the colon, mice were intra-nasally infected with 30 plaque forming units of the mouse-adapted H3N2 IAV strain Scotland/20/1974. PBS-treated mice served as controls. The colons were collected 7 days post-infection.
2019-12-01 | E-MTAB-6707 | biostudies-arrayexpress
Project description:The circulation of seasonal influenza A viruses (IAVs) in humans relies on effective evasion and subversion of the host immune response. While the evolution of seasonal H1N1 and H3N2 viruses to avoid humoral immunity is well characterized, relatively little is known about the evolution of innate immune antagonism phenotypes in these viruses. Numerous studies have established that only a small subset of infected cells are responsible for initiating the type I and type III interferon (IFN) response during IAV infection, emphasizing the importance of single cell studies to accurately characterize the IFN response during infection. We developed a flow cytometry-based method to examine transcriptional changes in IFN and interferon stimulated gene (ISG) expression at the single cell level. We observed that NS segments derived from seasonal H3N2 viruses are more efficient at antagonizing IFN signaling but less effective at suppressing IFN induction, compared to the pdm2009 H1N1 lineage. We compared a collection of NS segments spanning the natural history of the current seasonal IAV lineages, and demonstrate long periods of stability in IFN antagonism potential, punctuated by occasional phenotypic shifts. Altogether, our data reveal significant differences in how seasonal and pandemic H1N1 and H3N2 viruses antagonize the human IFN response at the single cell level.
2024-07-12 | GSE272070 | GEO
Project description:Influenza A Virus (IAV) is a recurring respiratory virus with antiviral therapies of limited use. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses with three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we mapped 332 IAV-human protein-protein interactions and identified 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza revealed several genes, including the structural scaffold protein AHNAK, with predicted loss-of-function variants that were also identified in our proteomic analyses. Of our identified host factors, 54 significantly altered IAV infection upon siRNA knockdown, and two factors, COPB1 and AHNAK, were also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppressed IAV replication, with three targeting ATP6V1A, CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. This project includes the global proteomic data (abundance and phosphorylation), the AP-MS data has been submitted separately as its own dataset and has its own dataset identifier.
2023-07-25 | PXD035900 | Pride
Project description:A novel avian-origin H7N9 influenza A virus (IAV) emerged in China in early 2013 causing mild to lethal human respiratory infections. H7N9 originated from multiple reassortment events between avian viruses and carries genetic markers of human adaptation. Determining whether H7N9 induces a host-response closer to human or avian IAV is important to better characterize this emerging virus. Here we compared the human lung epithelial cell response to infection with A/Anhui/01/13 (H7N9) or highly pathogenic avian-origin H5N1, H7N7, or human seasonal H3N2 IAV.
2014-01-16 | GSE49840 | GEO
Project description:Glycosylation is critical for viral-host cell interactions in influenza A virus (IAV) infection, but we lack a comprehensive understanding of how IAV infection shapes the host glycoproteome and the implications of these changes. Here, we used a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to perform proteomic, glycomic, and glycoproteomic characterisation of the dynamic subcellular responses to an in vitro time course infection of human A549 cells with two IAV strains (A/X-31, H3N2; and A/Puerto Rico/8/1934, H1N1). IAV infection resulted in only modest changes to the subcellular proteome, but robust and significant changes to the host secreted and organelle glycome and glycoproteome. Infection with either virus resulted in increased proportions of oligomannose, paucimannose, and phosphorylated glycans; reduced branching and length of complex glycans; and a widespread reduction in sialic acid across the N- and O-glyco(proteo)me. Reduced sialylation was consistent with desialylation of glycans by viral neuraminidase (NA), but with specific features of the glycan and protein controlling the extent of desialylation. Desialylation was greater when glycans were fucosylated; when the sialic acid was attached via an ⍺2,3 linkage or positioned on the ⍺3 arm; on larger, more complex glycans; and when present on proteins we infer are more accessible to IAV NA. Subtle, but prolonged activation of the unfolded protein response led to a doubling of oligomannose N-glycosylation. Glycans were shorter in infection, implicating IAV-induced disruption of Golgi glycoprotein flux as a mechanism to reduce host glycoprotein sialylation and promote virion release, independent of NA activity. Our data provide important insights into the host glycoproteome during influenza virus infection, furthering our understanding of how influenza NA acts upon host glycans, and how cell stresses in infection perturb key mediators of protein stability and function, cell signalling and immunity.
2026-08-27 | PXD072704 | Pride