Dataset Information

Patient-based transcriptome-wide analysis identify interferon and ubiquination pathways as potential predictors of influenza A disease severity.

ABSTRACT:

Background

The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions.

Methodology/principal findings

Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N?=?11), moderate (N?=?40) and mild (N?=?83) symptoms were compared with the febrile patients of unknown etiology (N?=?73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis.

Conclusion/significances

The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.

SUBMITTER: Hoang LT

PROVIDER: S-EPMC4218794 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Patient-based transcriptome-wide analysis identify interferon and ubiquination pathways as potential predictors of influenza A disease severity.

Hoang Long Truong LT Tolfvenstam Thomas T Ooi Eng Eong EE Khor Chiea Chuen CC Naim Ahmand Nazri Mohamed AN Ho Eliza Xin Pei EX Ong Swee Hoe SH Wertheim Heiman F HF Fox Annette A Van Vinh Nguyen Chau C Nghiem Ngoc My NM Ha Tuan Manh TM Thi Ngoc Tran Anh A Tambayah Paul P Lin Raymond R Sangsajja Chariya C Manosuthi Weerawat W Chuchottaworn Chareon C Sansayunh Piamlarp P Chotpitayasunondh Tawee T Suntarattiwong Piyarat P Chokephaibulkit Kulkanya K Puthavathana Pilaipan P de Jong Menno D MD Farrar Jeremy J van Doorn H Rogier HR Hibberd Martin Lloyd ML

PloS one 20141103 11

<h4>Background</h4>The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions.<h4>Methodology/principal findings< ...[more]

PMID: 25365328

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Project description:BackgroundThe Chr17q12-21.2 region is the strongest and most consistently associated region with asthma susceptibility. The functional genes or single nucleotide polymorphisms (SNPs) are not obvious due to linkage disequilibrium.ObjectivesWe sought to comprehensively investigate whole-genome sequence and RNA sequence from human bronchial epithelial cells to dissect functional genes/SNPs for asthma severity in the Severe Asthma Research Program.MethodsExpression quantitative trait loci analysis (n = 114), correlation analysis (n = 156) of gene expression and asthma phenotypes, and pathway analysis were performed in bronchial epithelial cells and replicated. Genetic association for asthma severity (426 severe vs 531 nonsevere asthma) and longitudinal asthma exacerbations (n = 273) was performed.ResultsMultiple SNPs in gasdermin B (GSDMB) associated with asthma severity (odds ratio, >1.25) and longitudinal asthma exacerbations (P < .05). Expression quantitative trait loci analyses identified multiple SNPs associated with expression levels of post-GPI attachment to proteins 3, GSDMB, or gasdermin A (3.1 × 10-9 <P < 1.8 × 10-4). Higher expression levels of GSDMB correlated with asthma and greater number of exacerbations (P < .05). Expression levels of GSDMB correlated with genes involved in IFN signaling, MHC class I antigen presentation, and immune system pathways (false-discovery rate-adjusted P < .05). rs1031458 and rs3902920 in GSDMB colocalized with IFN regulatory factor binding sites and associated with GSDMB expression, asthma severity, and asthma exacerbations (P < .05).ConclusionsBy using a unique set of gene expression data from lung cells obtained using bronchoscopy from comprehensively characterized subjects with asthma, we show that SNPs in GSDMB associated with asthma severity, exacerbations, and GSDMB expression levels. Furthermore, its expression levels correlated with asthma exacerbations and antiviral pathways. Thus, GSDMB is a functional gene for both asthma susceptibility and severity.

Dataset Information

Patient-based transcriptome-wide analysis identify interferon and ubiquination pathways as potential predictors of influenza A disease severity.

Background

Methodology/principal findings

Conclusion/significances

Publications

Patient-based transcriptome-wide analysis identify interferon and ubiquination pathways as potential predictors of influenza A disease severity.

Similar Datasets

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