학술논문

Dual RNA-seq reveals viral infections in asthmatic children without respiratory illness which are associated with changes in the airway transcriptome
Document Type
article
Source
Genome Biology. 18(1)
Subject
Medical Microbiology
Bioinformatics and Computational Biology
Biomedical and Clinical Sciences
Biological Sciences
Infectious Diseases
Vaccine Related
Prevention
Emerging Infectious Diseases
Pediatric
Biotechnology
Lung
Genetics
Biodefense
2.2 Factors relating to the physical environment
2.1 Biological and endogenous factors
Aetiology
Respiratory
Infection
Inflammatory and immune system
Good Health and Well Being
Asthma
Case-Control Studies
Child
Gene Expression Profiling
Gene Expression Regulation
Viral
High-Throughput Nucleotide Sequencing
Host-Pathogen Interactions
Humans
RNA Virus Infections
RNA Viruses
Respiratory Mucosa
Respiratory Tract Infections
Sequence Analysis
RNA
Transcriptome
Asymptomatic
Virus
Airway epithelium
RNA-seq
Children
Host response
Host-virus interactions
Environmental Sciences
Information and Computing Sciences
Bioinformatics
Language
Abstract
BackgroundRespiratory illness caused by viral infection is associated with the development and exacerbation of childhood asthma. Little is known about the effects of respiratory viral infections in the absence of illness. Using quantitative PCR (qPCR) for common respiratory viruses and for two genes known to be highly upregulated in viral infections (CCL8/CXCL11), we screened 92 asthmatic and 69 healthy children without illness for respiratory virus infections.ResultsWe found 21 viral qPCR-positive and 2 suspected virus-infected subjects with high expression of CCL8/CXCL11. We applied a dual RNA-seq workflow to these subjects, together with 25 viral qPCR-negative subjects, to compare qPCR with sequencing-based virus detection and to generate the airway transcriptome for analysis. RNA-seq virus detection achieved 86% sensitivity when compared to qPCR-based screening. We detected additional respiratory viruses in the two CCL8/CXCL11-high subjects and in two of the qPCR-negative subjects. Viral read counts varied widely and were used to stratify subjects into Virus-High and Virus-Low groups. Examination of the host airway transcriptome found that the Virus-High group was characterized by immune cell airway infiltration, downregulation of cilia genes, and dampening of type 2 inflammation. Even the Virus-Low group was differentiated from the No-Virus group by 100 genes, some involved in eIF2 signaling.ConclusionsRespiratory virus infection without illness is not innocuous but may determine the airway function of these subjects by driving immune cell airway infiltration, cellular remodeling, and alteration of asthmogenic gene expression.