Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1288556 | ENA |
REPOSITORIES: ENA
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Project description:Analyses of AP-MS experiments performed in HEK 293T cells infected with the influenza A/WSN/33 virus. In half of the experiments the virus was modified to contain a C-terminal Strep tag on the polymerase subunit PB2. Full details in York et al. 'Interactome analysis of the influenza A virus transcription/replication machinery identifies protein phosphatase 6 as a cellular factor required for efficient virus replication.'
2014-06-16 | MSV000078741 | MassIVE
Project description:Influenza A virus is mainly transmitted through the respiratory route and can cause severe illness in humans. Proteins encoded by influenza A virus can interact with cellular factors and dysregulate host biological processes to facilitate viral replication and pathogenicity. The influenza viral PA protein is not only a subunit of influenza viral polymerase but also a virulence factor involved in pathogenicity during infection. To explore the role of the influenza virus PA protein in regulating host biological processes, we conducted immunoprecipitation and LC-MS/MS to globally identify cellular factors that interact with the PA proteins of the influenza A H1N1, 2009 pandemic H1N1, H3N2, and H7N9 viruses. The results demonstrated that proteins located in the mitochondrion, proteasome, and nucleus are associated with the PA protein. We further discovered that the PA protein is located in mitochondria by immunofluorescence and mitochondrial fractionation and that overexpression of the PA protein reduces mitochondrial respiration. In addition, our results revealed the interaction between PA and the mitochondrial matrix protein PYCR2 and the antiviral role of PYCR2 during influenza A virus replication. Moreover, we found that the PA protein could also trigger autophagy and disrupt mitochondrial homeostasis. Overall, our research revealed the impacts of the influenza A virus PA protein on mitochondrial function and autophagy.
2024-06-23 | PXD050585 | Pride
Project description:Seasonal epidemics of influenza A virus are a major cause of severe illness and are of high socio-economic relevance. For the design of effective anti-viral therapies, a detailed knowledge of cellular pathways perturbed by virus infection is critical. We performed comprehensive expression and organellar proteomics experiments to identify new protein targets and cellular pathways affected by influenza A virus. Type I as well as type II interferon pathways were upregulated upon infection, affecting amongst others poly ADP-ribose polymerase transcription factors and ubiquitin-like modifiers. In addition, influenza A virus had a major influence on the subcellular localization of proteins and complexes. The vesicular compartment appeared expanded upon infection and in particular the composition of autophagsomes was altered, virus infection leading to targeting of ribosomes to autophagosomes.
2018-07-12 | PXD007809 | Pride
Project description:Infection with a single influenza A virus (IAV) is only rarely sufficient to initiate productive infection. Here, we exploit both single cell approaches and whole-animal systems to show that the extent of IAV reliance on multiple infection varies with virus strain and host species. Influenza A/guinea fowl/HK/WF10/99 (H9N2) [GFHK99] virus exhibits strong dependence on collective interactions in mammalian systems. This reliance focuses viral progeny production within coinfected cells and therefore results in frequent genetic exchange through reassortment. In contrast, GFHK99 virus has greatly reduced dependence on multiple infection in avian systems, indicating a role for host factors in viral collective interactions. Genetic mapping implicated the viral polymerase as a major driver of multiple infection dependence. Mechanistically, quantification of incomplete viral genomes showed that their complementation only partly accounts for the observed reliance on coinfection. Indeed, even when all polymerase components are detected in single cell mRNA sequencing, robust polymerase activity of GFHK99 virus in mammalian cells is reliant on multiple infection. In sum, IAV collective interactions not only augment reassortment, but can also overcome species-specific barriers to infection. These findings underscore the importance of virus-virus interactions in IAV infection, evolution and emergence. We used a single-cell sequencing platform (10x Genomics) to elucidate the differential infection rate of an avian influenza A virus on an avian cell line (DF1) and a mammalian (MDCK) cell line. Our work on IAV reassortment has raised new questions about the fundamental strategies that drive influenza virus evolution. Our data indicate that a large majority of influenza virus genomesare incomplete within cells, comprising less than the eight complete segments normally found in a replication competent infectious viral particle. This led us to ask: what underlying mechanisms give rise to incomplete genomes? What constitute an infectious unit? What are the implications for viral diversification, evolution and spread. By addressing these questions, we will advance he field by deepening our understanding how viral infections are initiated and propagated.
2020-06-16 | GSE135553 | GEO
Project description:Encoding only ten major proteins, Influenza A virus (IAV) gains access to both the cell and nucleus, replicates its eight genomic segments, then enters the cytoplasm to assemble and egress. This is achieved through an expansive network of interactions with the host and a coordinated production of viral components. Here we show that upon infection, primary transcription of the virus results in the accumulation of the splice product, Nuclear Export Protein (NEP), which associates with the viral polymerase leading to the synthesis of segment-specific small viral RNAs (svRNAs). Here we demonstrate that svRNA biology is responsible for coordinating segment-specific amplification and is predominantly required for amplification of the three larger polymerase segments. Generation of svRNA ambiguity results in predictable changes in segment-specific vRNA levels and up to a five log attenuation. Together, these data elucidate the molecular function of svRNAs as essential mediators responsible for maintaining a stoichiometric balance between genomic segments and establish these small RNAs as functional components of the virus.
2017-06-14 | GSE83289 | GEO
Project description:Influenza A virus (IAV) is a threat to mankind because it generates yearly epidemics and poorly predictable sporadic pandemics with catastrophic potential. Influenza has a small RNA genome (~14 Kb) composed of 8 mini-chromosomes (segments). Segments encode both structural proteins and proteins expressed only during infection. Segments are constituted by a 5’UTR followed by a coding region and a 3’UTR. Transcription of IAV RNA into mRNA depends on host RNA Polymerase II, as the viral polymerase cleaves 5’ capped cellular nascent transcripts to be used as primers to initiate mRNA synthesis. We hypothesized that host nascent transcripts bearing AUG could generate upstream ORFs in the viral segments, a phenomenon that would depend on the translatability of the viral 5’UTRs. Using orthogonal datasets we report the existence of this mechanism, which generate host-virus chimeric proteins. We show that most segments encode proteins in this manner, expanding the proteome diversity of IAV in infected cells. Host-virus chimeric proteins are conserved across IAV strains, pointing to an evolutionary conservation of function achieved by sampling of the evolutionary space before gene fixation. Thus, we discover a mechanism that generate human-virus chimeric proteins during infection.
2020-06-25 | GSE128519 | GEO
Project description:To further understand the molecular pathogenesis of the 2009 pandemic H1N1 influenza virus infection, we profiled cellular miRNAs of lung tissue from BALB/c mice infected with influenza virus BJ501 and a mouse-adapted influenza virus A/Puerto Rico/8/34 (H1N1)(PR8) as a comparison.
2013-04-17 | GSE46087 | GEO
Project description:Influenza A virus encodes promoters in both the sense and antisense orientations. These support the generation of new genomes, antigenomes, and mRNA transcripts. Characterization of the influenza promoters using minimal replication assays—transfections with viral polymerase, nucleoprotein, and a genomic template—defined their sequence as 13nt at the 5’ end of the viral genomic RNA (U13) and 12nt at the 3’ end (U12).Other than a single position the U12 and U13 sequences are identical between all eight RNA molecules that comprise the segmented influenza genome.Nevertheless, each segment can exhibit different transcriptional dynamics despite possessing identical promoters.Minimal replication assays lack the influenza protein NS2, which can modulate transcription and replication differentially between influenza segments.This suggests that NS2 expression may redefine the influenza A virus promoter.In this work we assess how internal regions of sequence in two genomic segments, HA and PB1, may contribute to NS2-dependent replication as well as map such interactions down to individual nucleotides in PB1. We find that the expression of NS2 significantly alters sequence requirements for efficient replication beyond the identical U12 and U13 sequence, providing a mechanism for the divergent replication and transcription dynamics across the influenza A virus genome.
2024-09-10 | GSE276697 | GEO
Project description:Influenza A virus is a kind of single negative-stranded RNA virus which belongs to the Orthomyxoviridae family. It can cause localized outbreak or worldwide epidemic in a short time for its great contagiosity, fast spread speed and a wide range of host, and H1N1 influenza virus is a strong pathogenic subtype of influenza A virus. Influenza A virus infection has been shown to alter miRNA expression both in cultured cells and in animal models. We used microRNA microarrays to detail the programme of microRNA expression and identified distinct classes of differentially regulated microRNAs during this process.
2014-10-21 | GSE62495 | GEO
Project description:The nuclear RNA exosome is an essential multi-subunit complex that controls RNA homeostasis. Congenital mutations in exosome genes are associated with neurodegenerative diseases. Here, we show that transient depletion of nuclear RNA exosome subunits in epithelial cells inhibits influenza virus replication. Similarly, viral biogenesis was suppressed in cells derived from mice with conditional ablation of the RNA exosome subunit Exosc3. Furthermore, patient-derived cells with a congenital EXOSC3 mutation were less susceptible to influenza virus infection. Using proteomics and next generation sequencing during infection, we show that the viral polymerase complex (PA, PB2, PB1) co-opts the nuclear RNA exosome complex and cellular RNAs en route to 3’ end degradation. Mechanistically, the nuclear RNA exosome coordinates the initial steps of viral transcription with RNAPII at host promoters. Exosome deficiency uncouples chromatin targeting of the viral polymerase complex and the formation of cellular:viral RNA hybrids, which are essential RNA intermediates that license transcription of antisense genomic viral RNAs. Overall, we discovered a critical nexus between an essential component of the influenza virus (polymerase) and an essential component of the cell (exosome), alteration of which leads to breakage of host-pathogen symmetry and a lose-lose scenario (viral impairment and neurodegeneration).
2017-05-08 | GSE96677 | GEO