Differential miRNA expression profiling of highly pathogenic avian influenza virus H5N1 infected chicken lungs reveals critical microRNAs, biological pathways and genes involved in the molecular pathogenesis.
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ABSTRACT:
SUBMITTER: Mishra A
PROVIDER: S-EPMC9243614 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Exosomes are membrane vesicles containing proteins, lipids, DNA, mRNA, and micro RNA (miRNA). Exosomal miRNA from donor cells can regulate the gene expression of recipient cells. Here, Ri chickens were divided into resistant (Mx/A; BF2/B21) and susceptible (Mx/G; BF2/B13) trait by genotyping of Mx and BF2 genes. Then, Ri chickens were infected with H5N1, a highly pathogenic avian influenza virus (HPAIV). Exosomes were purified from blood serum of resistant chickens for small RNA sequencing. Sequencing data were analysed using FastQCv0.11.7, Cutadapt 1.16, miRBase v21, non-coding RNA database, RNAcentral 10.0, and miRDeep2. Differentially expressed miRNAs were determined using statistical methods, including fold-change, exactTest using edgeR, and hierarchical clustering. Target genes were predicted using miRDB. Gene ontology analysis was performed using gProfiler. Twenty miRNAs showed significantly different expression patterns between resistant control and infected chickens. Nine miRNAs were up-regulated and 11 miRNAs were down-regulated in the infected chickens compared with that in the control chickens. In target gene analysis, various immune-related genes, such as cytokines, chemokines, and signalling molecules, were detected. In particular, mitogen-activated protein kinase (MAPK) pathway molecules were highly controlled by differentially expressed miRNAs. The result of qRT-PCR for miRNAs was identical with sequencing data and miRNA expression level was higher in resistant than susceptible chickens. This study will help to better understand the host immune response, particularly exosomal miRNA expression against HPAIV H5N1 and could help to determine biomarkers for disease resistance.
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Project description:This study is planned to characterize the proteome profile of HPAI H5N1 virus infected chicken lung tissues to identify the molecular pathogenesis and proteomic determinant associate with disease progression in susceptible host.
2022-03-02 | PXD010358 | Pride
Project description:The underlying molecular mechanisms of pathogenesis and outcome of disease to different pathotypes of H5N1 influenza infection in ducks remain unclear. For that, we studied genome wide host gene expression of lung tissues infected with A/duck/India/02CA10/2011(AD2011) H5N1 virus and A/duck/Tripura/103597/2008 (AD2008) H5N1 virus in ducks using custom designed microarray. AD2011 is highly pathogenic whereas AD2008 is low pathogenic to ducks. Comparative analysis of differentially expressed genes revealed that 688 genes were commonly expressed, 877 and 1556 genes are uniquely expressed to infection with AD2011 and AD2008 virus isolate, respectively. The up-regulation of cytokines genes OAS, IL1B, IL17, IFITM2, CCL4, CXCR4, STAT3, TGFB1 and TGFB2 in the lungs tissues may cause high mortality in ducks infected with AD2011 virus. The expression of important antiviral immune genes IFIT5, IFITM5, RSAD2, EIF2AK2 (PKR), Mx, β-defensins, TRIM23 and SLC16A3 to AD2008 infection, but not in AD2011 infection, cause the host may fine-tune their innate immune responses and prevent from cytokines storms and tissue damage. Several immune related Gene ontology (GO) terms and immune pathways activated were qualitatively similar but quantitatively different to both virus infections. Based on these findings, we conclude that subtle differences in host immune responses may determine the different outcome of H5N1 infection in ducks.
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Project description:The molecular pathogenesis of avian influenza infection varies greatly with individual bird species and virus strain. The molecular pathogenesis of the highly pathogenic avian influenza virus (HPAIV) or the low pathogenic avian influenza virus (LPAIV) infection in avian species remains poorly understood. Thus, global immune response of chickens infected with HPAI H5N1 (A/duck/India/02CA10/2011) and LPAI H9N2 (A/duck/India/249800/2010) viruses was studied using microarray to identify crucial host genetic components responsive to these infection. HPAI H5N1 virus induced excessive expression of type I IFNs (IFNA and IFNG), cytokines (IL1B, IL18, IL22, IL13, and IL12B), chemokines (CCL4, CCL19, CCL10, and CX3CL1) and IFN stimulated genes (OASL, MX1, RSAD2, IFITM5, IFIT5, GBP 1, and EIF2AK) in lung tissues. This dysregulation of host innate immune genes may be the critical determinant of the severity and the outcome of the influenza infection in chickens. In contrast, the expression levels of most of these genes was not induced in the lungs of LPAI H9N2 virus infected chickens. This study indicated the relationship between host immune genes and their roles in pathogenesis of HPAIV infection in chickens.
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Project description:The underlying molecular mechanisms of pathogenesis and outcome of disease to different pathotypes of H5N1 influenza infection in ducks remain unclear. For that, we studied genome wide host gene expression of lung tissues infected with A/duck/India/02CA10/2011(AD2011) H5N1 virus and A/duck/Tripura/103597/2008 (AD2008) H5N1 virus in ducks using custom designed microarray. AD2011 is highly pathogenic whereas AD2008 is low pathogenic to ducks. Comparative analysis of differentially expressed genes revealed that 688 genes were commonly expressed, 877 and 1556 genes are uniquely expressed to infection with AD2011 and AD2008 virus isolate, respectively. The up-regulation of cytokines genes OAS, IL1B, IL17, IFITM2, CCL4, CXCR4, STAT3, TGFB1 and TGFB2 in the lungs tissues may cause high mortality in ducks infected with AD2011 virus. The expression of important antiviral immune genes IFIT5, IFITM5, RSAD2, EIF2AK2 (PKR), Mx, β-defensins, TRIM23 and SLC16A3 to AD2008 infection, but not in AD2011 infection, cause the host may fine-tune their innate immune responses and prevent from cytokines storms and tissue damage. Several immune related Gene ontology (GO) terms and immune pathways activated were qualitatively similar but quantitatively different to both virus infections. Based on these findings, we conclude that subtle differences in host immune responses may determine the different outcome of H5N1 infection in ducks. Agilent Custom Duck Gene Expression 8X60k (AMADID: G4102A_059612) designed by Genotypic Technology Private Limited , Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)
2016-07-04 | E-GEOD-65230 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-03-04 | GSE53932 | GEO
Project description:Highly pathogenic avian influenza virus (HPAIV) H5N1 has been endemic in Egypt since 2006, and there is increasing concern for its potential to become highly transmissible among humans. Infection by HPAIV H5N1 has been described in experimentally challenged birds. However, the pathogenicity of the H5N1 isolated in Egypt has never been reported in naturally infected chickens and ducks. Here we report a 2013 outbreak of HPAIV H5N1 in commercial poultry farms and backyards in Sharkia Province, Egypt. The main symptoms were ecchymosis on the shanks and feet, cyanosis of the comb and wattles, subcutaneous edema of the head and neck for chickens, and nervous signs (torticollis) for ducks. Within 48-72 hrs of the onset of illness, the average mortality rates were 22.8-30% and 28.5-40% in vaccinated chickens and non-vaccinated ducks, respectively. Tissue samples of chickens and ducks were collected for analyses with cross-section immunohistochemistry and real-time RT-PCR for specific viral RNA transcripts. While viral RNA was detected in nearly all tissues and sera collected, viral nucleoprotein was detected almost ubiquitously in all tissues, including testis. Interestingly, viral antigen was also observed in endothelial cells of most organs in chickens, and clearly detected in the trachea and brain in particular. Viral nucleoprotein was also detected in mononuclear cells of various organs, especially pulmonary tissue. We performed phylogenetic analyses and compared the genomic sequences of the hemagglutinin (HA) and nonstructural proteins (NS) among the isolated viruses, the HPAIV circulated in Egypt in the past and currently, and some available vaccine strains. Further analysis of deduced amino acids of both HA and NS1 revealed that our isolates carried molecular determinants of HPAIV, including the multibasic amino acids (PQGERRRK/KR*GLF) in the cleavage site in HA and glutamate at position 92 (D92E) in NS1. This is the first report of the pathogenicity of the HPAIVH5N1 strain currently circulating in naturally infected poultry in Egypt, which may provide unique insights into the viral pathogenesis in HPAIV-infected chickens and ducks.
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Project description:Highly pathogenic avian influenza A(H5N1) viruses have spread rapidly throughout North American flyways in recent months, affecting wild birds in over 40 states. We evaluated the pathogenicity and transmissibility of a representative virus using a ferret model and examined replication kinetics of this virus in human respiratory tract cells.
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Project description:Background & objectives:The susceptibility of influenza viruses to neuraminidase inhibitors (NAIs) is studied using enzyme-based assays, sequence analysis and in vitro and in vivo studies. Oseltamivir carboxylate (OC) is the active prodrug of the NAI oseltamivir. There is lack of information on the use of embryonated chicken eggs for studying susceptibility of highly pathogenic avian influenza (HPAI) H5N1 viruses to antiviral drugs. The aim of the present study was to assess the use of 10 day old embryonated chicken eggs for studying antiviral susceptibility of HPAI H5N1 viruses. Methods:Two HPAI H5N1 viruses isolated from India were used in the study. Fluorescence-based NAI assay was performed to determine antiviral susceptibility of these viruses. In ovo antiviral assays were carried out using 10 day old embryonated chicken eggs. The virus dilutions were incubated with 14 ?g/ml of OC and inoculated in the allantoic cavity. In the eggs, 50 per cent egg infectious dose (EID50) titres as well as mortality were quantitated. Results:The two viruses used were susceptible to OC in the NAI assay. It was found that there was a significant drop in EID50titres; however, no significant protection from mortality after OC treatment was observed. Interpretation & conclusions:By measuring viral titres, the egg model was suitable to study the susceptibility of HPAI viruses to antiviral drugs along with NAI assay. The present study highlights the use of eggs as a model to study susceptibility of HPAI viruses to OC.
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