Influenza A virus replicates productively in primary human kidney cells and induces factors and mechanisms related to regulated cell death and renal pathology observed in virus-infected patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE189735 | GEO | 2024/03/28
REPOSITORIES: GEO
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Project description:Background: Influenza A virus (IAV) is a segmented negative-stranded RNA virus that brings a potentially serious threat to public health and animal husbandry. Mast cells play an important role in both the inherent and adaptive immune response. Previous studies have indicated that mast cells support the productive replication of H1N1, H5N1, and H7N2. To date, the distinct molecular mechanism behind the pathogenesis in mast cells among the three different viruses has been poorly understood. Methods: We investigated the genomic profiles in detail and the dynamic change of genomes regulated by different subtypes of IAV in mouse mast cells using microassays in order to the distinct molecular mechanism behind the pathogenesis in mast cells among the three different viruses. Mouse mast cells (P815) were infected at a multiplicity of infection of 1 (infectious viruses/cell) and incubated for 12 hr before collection of total RNA and microarray anlaysis using the Affymetrix platforms. Any two of the three IAV-infected groups were compared to detect genomic distinct. Based on the results of microassays, the further verification was performed by real-time PCR and western blotting. Here, the mRNA levels of 5-HT, PKG and HIF-1 in P815 cells following H1N1, H5N1 and H7N2 infection were determined by real-time PCR. The protein levels of exosomes in P815 cells following H1N1, H5N1 and H7N2 infection were detected by western blotting. Results: Compared with any two of the three IAV-infected groups, much more differentially expressed genes (DEGs), cellular functions and signaling pathways were confirmd in H1N1 or H7N2 group, and H7N2 group showed the highest levels. However, few DEGs were detected as well as various cellular functions and signaling pathways were dramatically suppressed in H5N1 group. With an in-depth study on H1N1 and H7N2 group, we demonstrated the 5-HT signaling pathway and cGMP/PKG signaling pathway terms were enriched in P815 cells infected by H1N1 while HIF-1 signaling pathway terms were enriched in P815 cells infected by H7N2 virus. Furthermore, RT-qPCR results also showed significantly increased mRNA of 5-HT and PKG in H1N1-infected P815 cells as well as HIF-1 in H7N2-infected P815 cells. Besides, exosomes were highly secreted from H1N1-infected or H7N2-infected P815 cells. Conclusions: H1N1 and H7N2 viruses could result in a variety of DEGs in mast cells and activate various cellular functions and signaling pathways while H5N1 virus cause the few DEGs in mast cells as well as suppression of cellular functions and signaling pathways. Furthermore, 5-HT signaling pathway and cGMP/PKG signaling pathway were preferentially activated in P815 cells infected by H1N1 while HIF-1 signaling pathway were preferentially activated in P815 cells infected by H7N2 virus. In addition, exosomes were also preferentially secreted from H1N1-infected or H7N2-infected P815 cells that are potentially pivotal in innate immunity to fight IAV infection. The study provides novel information and insight into the distinct of molecular mechanism of H1N1, H5N1 and H7N2 viruses in mast cells from the perspective of genomic profiles.
2019-04-12 | GSE129623 | GEO
Project description:To investigate whether influenza A virus (IAV) infection alters cellular miRNA profiles, A549 cells were either mock-infected or infected with two different subtypes of IAV, A/Beijing/501/2009 (H1N1; MOI=5) and A/Vietnam/1194/2004 (H5N1; MOI=2), for 24 or 48 h. Total RNA was purified from cell samples, and microarray analysis of miRNAs was performed. The expression of selected miRNAs was further confirmed by quantitative real-time PCR.
2018-05-09 | GSE107186 | GEO
Project description:Circular RNAs (circRNAs) 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 circRNAs in the H1N1-infected cells by high-throughput sequencing
2023-08-07 | GSE181727 | GEO
Project description:Transcriptome analysis of mock or H1N1 IAV PR8 infected p53WT A549 and p53null A549-KO3 cells by Affymetrix GeneChip Human Transcriptome 2.0 Arrays to achieve a set of genes those are regulated by p53 and responsive to IAV infection. Influenza A virus infection activates cellular p53, however it has not been clear whether this process has pro- or anti- viral effects. In this study, using human isogenic p53 wildtype A549 cells and p53null A549-KO3 cells generated from the CRISPR/Cas9 technology, we report that p53null cells exhibit significantly reduced viral propagation property when infected with influenza A virus (H1N1/A/Puerto Rico/8/34). Here, using genome-wide microarray analysis we revealed that p53 regulates the expression of a large set of interferon-inducible genes, some of which are directly associated with viral infectivity and later experimentally validated to be responsible for p53-regulated IAV infectivity.
2018-05-31 | GSE106279 | GEO
Project description:Miao2010 - Innate and adaptive immune
responses to primary Influenza A Virus infection
This model is described in the article:
Quantifying the early immune
response and adaptive immune response kinetics in mice infected
with influenza A virus.
Miao H, Hollenbaugh JA, Zand MS,
Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ.
J. Virol. 2010 Jul; 84(13):
6687-6698
Abstract:
Seasonal and pandemic influenza A virus (IAV) continues to
be a public health threat. However, we lack a detailed and
quantitative understanding of the immune response kinetics to
IAV infection and which biological parameters most strongly
influence infection outcomes. To address these issues, we use
modeling approaches combined with experimental data to
quantitatively investigate the innate and adaptive immune
responses to primary IAV infection. Mathematical models were
developed to describe the dynamic interactions between target
(epithelial) cells, influenza virus, cytotoxic T lymphocytes
(CTLs), and virus-specific IgG and IgM. IAV and immune kinetic
parameters were estimated by fitting models to a large data set
obtained from primary H3N2 IAV infection of 340 mice. Prior to
a detectable virus-specific immune response (before day 5), the
estimated half-life of infected epithelial cells is
approximately 1.2 days, and the half-life of free infectious
IAV is approximately 4 h. During the adaptive immune response
(after day 5), the average half-life of infected epithelial
cells is approximately 0.5 days, and the average half-life of
free infectious virus is approximately 1.8 min. During the
adaptive phase, model fitting confirms that CD8(+) CTLs are
crucial for limiting infected cells, while virus-specific IgM
regulates free IAV levels. This may imply that CD4 T cells and
class-switched IgG antibodies are more relevant for generating
IAV-specific memory and preventing future infection via a more
rapid secondary immune response. Also, simulation studies were
performed to understand the relative contributions of
biological parameters to IAV clearance. This study provides a
basis to better understand and predict influenza virus
immunity.
This model is hosted on
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and identified by:
BIOMD0000000546.
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quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
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2021-10-05 | BIOMD0000000546 | BioModels
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:Type I and type III interferon (IFN) are important in regulating responses to viral infection. Type I IFN signaling is know to contribute to dendritic cell (DC) function, but the contribution of type III IFN remains unknown. To determine changes in migratory dendritic cell gene expression during influenza A virus (IAV) in the presence or absence of type I or type III (IFN) receptors, C57Bl/6 (WT) mice, mice lacking the type I IFN receptor (Ifnar-/-), and mice lacking the type III IFN receptor (Ifnlr-/-) were infected intranasally with 40 plaque forming units (PFU) IAV H1N1 strain A/PR/8/34 or mock infected. On day 4, lung-draining lymph nodes (dLN) were harvested, conventional DC were isolated, and mRNA sequencing (mRNAseq) was performed.
2018-12-28 | GSE124399 | 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:Viral infections affecting the upper or lower respiratory tract induce mucin production in the epithelial surfaces of the respiratory cells. However, a little is known about how mucins are produced on the surfaces of respiratory epithelial cells and affects viral replication. In the course of the investigation of the cellular responses in the early stage of Influenza A virus (IAV) infection, we found that two miRNAs, miR-221 and miR-17-3p, which target the mRNA of GalNAc transferase 3 (GALNT3), are rapidly down-regulated as early as 1.5 h post-infection. To understand the early host cell responses to the IAV infection, we performed miRNA microarray analysis using a human alveolar adenocarcinoma cell line, A549 cells, infected with influenza A/Puerto Rico/8/34 H1N1 (PR8) virus. We isolated the cellular RNAs at 0.5, 1.5 and 4.5 h post-infection and detected significant changes in the global profile of miRNA expression after infection with IAV. mouse embryonic fibroblasts. Each sample was run in duplicate.
2015-12-08 | E-GEOD-57508 | biostudies-arrayexpress
Project description:Neutrophils are essential cells of host innate immunity. Although the role of neutrophils in defense against bacterial and fungal infections is well characterized, there is relative paucity of information about their role against viral infections. Influenza A virus (IAV) infection can be associated with secondary bacterial co-infection, and it has long been posited that the ability of IAV to alter normal neutrophil function predisposes individuals to secondary bacterial infections. To better understand this phenomenon, we evaluated the interaction of pandemic or seasonal H1N1 IAV with human neutrophils isolated from healthy subjects. These viruses were ingested by human neutrophils and elicited changes in neutrophil gene expression that are consistent with an interferon-mediated immune response. Viability of neutrophils following co-culture with either pandemic and seasonal H1N1 IAV was similar for up to 18 h of culture. Notably, neutrophil exposure to seasonal IAV (but not pandemic IAV) primed these leukocytes for enhanced functions, including production of reactive oxygen species and bactericidal activity. Taken together, our results are at variance with the universal idea that IAV impairs neutrophil function directly to predispose individuals to secondary bacterial infections. Rather, we suggest some strains of IAV prime neutrophils for enhanced bacterial clearance.
2017-12-05 | GSE100865 | GEO