Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Host chaperones can define the fitness of adaptive influenza variants

ABSTRACT: The threat of viral pandemics demands a comprehensive understanding of evolution at the host-pathogen interface. Here, we systematically show that the accessibility of adaptive mutations in influenza nucleoprotein at fever-like temperatures is mediated by host chaperones. Particularly noteworthy, we observe that the Pro283 nucleoprotein variant, which is conserved across human flu strains, confers resistance to the MxA antiviral-restriction factor, and critically contributed to the pathogenicity of the 1918 pandemic flu, is rendered unfit by host chaperone depletion. This fitness loss is linked to biophysical defects that chaperones cannot address when heat shock factor-I is inhibited. Thus, host chaperones can be hijacked by viruses to un-couple biophysically deleterious consequences of mutations from the benefits of immune escape. In summary, host chaperones play a central role in shaping influenza adaptation, with implications for the evolution of other viruses, for viral host-switching, and for the design of antiviral strategies refractory to resistance.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE113649 | GEO | 2018/09/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Ambion and Exiqon miRNA profiling

Project description:Influenza A virus induces endogenous miR-141 to undermine MxA antiviral activity

2015-01-01 | GSE16638 | GEO

A Systems Approach to Understanding Human Rhinovirus and Influenza Virus Infection

Project description:Human rhinovirus and influenza virus infections of the upper airway lead to colds and the flu and can trigger exacerbations of lower airway diseases including asthma and chronic obstructive pulmonary disease. Despite modest advances in the diagnosis and treatment of infections by these viruses, novel diagnostic and therapeutic targets are still needed to differentiate between the cold and the flu, since the clinical course of influenza can be severe while that of rhinovirus is usually more mild. In our investigation of influenza and rhinovirus infection of human respiratory epithelial cells, we used a systems approach to identify the temporally changing patterns of host gene expression from these viruses. After infection of human bronchial epithelial cells (BEAS-2B) with rhinovirus, influenza virus or co-infection with both viruses, we studied the time-course of host gene expression changes over three days. From these data, we constructed a transcriptional regulatory network model that revealed shared and unique host responses to these viral infections such that after a lag of 4-8 hours, most cell host responses were similar for both viruses, while divergent host cell responses appeared after 24-48 hours. The similarities and differences in gene expression after epithelial infection of rhinovirus, influenza virus, or both viruses together revealed qualitative and quantitative differences in innate immune activation and regulation. These differences help explain the generally mild outcome of rhinovirus infections compared to influenza infections which can be much more severe. Human bronchial epithelial cells (BEAS-2B) were infected with rhinovirus, influenza virus or both viruses and RNAs were then profiled at 10 time points (2, 4, 6, 8, 12, 24, 26, 48, 60 and 72hrs)

2015-12-21 | E-GEOD-71766 | biostudies-arrayexpress

A Systems Approach to Understanding Human Rhinovirus and Influenza Virus Infection

2015-12-21 | GSE71766 | GEO

Host Proteostasis Modulates Influenza Evolution

Project description:Predicting and constraining RNA virus evolution require understanding the molecular factors that define the mutational landscape accessible to these pathogens. RNA viruses typically have high mutation rates, resulting in frequent production of protein variants with compromised biophysical properties. Their evolution is necessarily constrained by the consequent challenge to protein folding and function. We hypothesize that host proteostasis mechanisms, may be significant determinants of the fitness of viral protein variants, serving as a critical force shaping viral evolution. Here, we test this hypothesis by propagating influenza in host cells displaying chemically-controlled, divergent proteostasis environments. We find that both the nature of selection on the influenza genome and the accessibility of specific mutational trajectories are significantly impacted by host proteostasis. These findings provide new insights into features of host–pathogen interactions that shape viral evolution, and into the potential design of host proteostasis-targeted antiviral therapeutics that are refractory to resistance.

2017-11-15 | GSE102797 | GEO

Reduced Nucleoprotein availability impairs negative-sense RNA virus replication and promotes host recognition

Project description:Negative-sense RNA viruses (NSVs) rely on prepackaged viral RNA-dependent RNA polymerases (RdRp) to replicate and transcribe their viral genomes. Their replication machinery consists of an RdRp bound to viral RNA which is wound around a nucleoprotein (NP) scaffold, forming a viral ribonucleoprotein complex. NSV NP is known to regulate transcription and replication of genomic RNA, however its role in maintaining and protecting the viral genetic material is unknown. Here, we exploited host microRNA expression to target NP of influenza A virus and Sendai virus to ascertain how this would impact genomic levels and the host response to infection. We find that in addition to inducing a drastic decrease in genome replication, the antiviral host response in the absence of NP is dramatically enhanced. Additionally, our data shows that insufficient levels of NP prevent the replication machinery of these NSVs to process full-length genomes, resulting in aberrant replication products which form pathogen-associated molecular patterns in the process. These dynamics facilitate immune recognition by cellular pattern recognition receptors leading to a strong host antiviral response. Moreover, we observe that the consequences of limiting NP levels are universal amongst NSVs including Ebola virus, Lassa virus and Measles virus. Overall, these results provide new insights into viral genome replication of negative-sense RNA viruses and highlight novel avenues towards developing effective antiviral strategies, adjuvants, and/or live-attenuated vaccines.

2021-02-02 | GSE165340 | GEO

Genome-wide analysis of gene expression in human macrophages in response to infection with influenza A viruses expressing full length or truncated non-structural protein NS1.

Project description:Analysis of gene expression in human macrophages infected with influenza A viruses expressing full length or truncated NS1 protein. The hypothesis tested was that C-terminal truncations of viral NS1 protein attenuate the capability of NS1 to limit activation of host antiviral and immune response genes. Cells were infected with influenza A/WSN/33 viruses expressing wild type NS1 protein (WSN-230), NS1 protein of 220 aa long (WSN-220) and NS1 protein of 202 aa long (WSN-202) on non-infected (Mock) Total RNA isolated from macrophages after 8 hours of infection with wild type or mutant influenza A virus (multiplicity of infection = 2)

2014-10-08 | E-GEOD-62127 | biostudies-arrayexpress

Genome-wide analysis of gene expression in human macrophages in response to infection with influenza A viruses expressing full length or truncated non-structural protein NS1.

2014-10-08 | GSE62127 | GEO

Single-cell analysis reveals lasting immunological consequences of influenza infection and respiratory immunisation in the pig lung

Project description:The pig is a natural host for influenza viruses and integrally involved in virus evolution through interspecies transmissions between humans and swine. We employed scRNA-seq and flow cytometry to characterize the major leucocyte subsets in bronchoalveolar lavage (BAL), twenty-one days after H1N1pdm09 infection or respiratory immunization with an adenoviral vector vaccine expressing haemagglutinin and nucleoprotein with or without IL-1β. Mapping scRNA-seq clusters from BAL onto those previously described in peripheral blood facilitated annotation and highlighted differences between tissue resident and circulating immune cells. ScRNA-seq data and functional assays revealed lasting impacts of immune challenge on BAL populations. First, mucosal administration of IL-1β reduced the number of functionally active Treg. Second, influenza infection upregulated IFI6 in BAL cells, decreasing their susceptibility to virus replication in vitro. Our data provide a reference map of BAL cells following respiratory infection or immunization in a highly relevant large animal model for respiratory virus infection.

2024-06-14 | GSE249866 | GEO

Acute lung injury results from innate sensing of viruses by an ER stress pathway

Project description:Incursions of new pathogenic viruses into humans from animal reservoirs are occurring with alarming frequency. The molecular underpinnings of immune recognition, host responses, and pathogenesis in this setting arepoorly understood. We studied pandemic influenza viruses to determine the mechanism by which increasing glycosylation during evolution of surface proteins facilitates diminished pathogenicity in adapted viruses. ER stressduring infection with poorly glycosylated pandemic strains activated the unfolded protein response, leading to inflammation, acute lung injury, and mortality. Seasonal strains or viruses engineered to mimic adapted viruses displaying excess glycans on the hemagglutinin did not cause ER stress, allowing preservation of the lungs and survival. We propose that ER stress resultingfrom recognition of non-adapted viruses is utilized to discriminate “non-self” at the level of protein-processing and to activate immune responses, with unintended consequences on pathogenesis. Understanding this mechanism should improve strategies for treating acute lung injury from zoonotic viral infections. Lung transcription analysis of Influenza A virus infected mice.

2015-07-06 | E-GEOD-65075 | biostudies-arrayexpress

Effect of miR-144/miR451 expression on TC-1 lung epithelial cell responses to influenza infection for 24 hours [Expression]

Project description:Antiviral responses must be regulated to rapidly defend against infection while minimizing inflammatory damage, but the mechanisms for establishing the magnitude of response within an infected cell are not well understood. miRNAs are small non-coding RNAs that negatively regulate protein levels by binding target sequences on their cognate mRNA. Here we identify miR-144 as a negative regulator of the host antiviral response. Ectopic expression of miR-144 resulted in increased replication of three RNA viruses, influenza, EMCV, and VSV, in primary mouse lung epithelial cells. To elucidate the mechanism whereby miR-144 increases influenza replication within lung epithelial cells, TC-1 cells stably over-expressing miR-144 were infected with influenza A for 24 hours and the transcriptional profile was compared with those of infected control cells. This systems biology approach identified the transcriptional network regulated by miR-144 and demonstrate that it controls the TRAF6/IRF7 antiviral response by post-transcriptionally suppressing TRAF6 levels. In vivo ablation of miR-144 reduced influenza replication within the lung. TC-1 lung epithelial cells stably expressing miR144+miR451 or control vector were unstimulated (n=1) or infected with Influenza A/PR/8/34 (MOI=5) for 24 hours (n=3).

2012-07-31 | E-GEOD-31955 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data