Dual RNA-seq reveals viral infections in asthmatic children without respiratory illness which are associated with changes in the airway transcriptome

There is a growing interest in unraveling gene expression mechanisms leading to viral host invasion and infection progression. Current findings reveal that long non-coding RNAs (lncRNAs) are implicated in the regulation of the immune system by influencing gene expression through a wide range of mechanisms. By mining whole-transcriptome shotgun sequencing (RNA-seq) data using machine learning approaches, we detected two lncRNAs (ENSG00000254680 and ENSG00000273149) that are downregulated in a wide range of viral infections and different cell types, including blood monocluclear cells, umbilical vein endothelial cells, and dermal fibroblasts. The efficiency of these two lncRNAs was positively validated in different viral phenotypic scenarios. These two lncRNAs showed a strong downregulation in virus-infected patients when compared to healthy control transcriptomes, indicating that these biomarkers are promising targets for infection diagnosis. To the best of our knowledge, this is the very first study using host lncRNAs biomarkers for the diagnosis of human viral infections.

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Automated Isoform Diversity Detector (AIDD): A pipeline for investigating transcriptome diversity of RNA-seq data

10.1101/2020.01.22.915348 ◽

2020 ◽

Author(s):

Noel-Marie Plonski ◽

Emily Johnson ◽

Madeline Frederick ◽

Heather Mercer ◽

Gail Fraizer ◽

...

Keyword(s):

Rna Editing ◽

Large Scale ◽

Neural Progenitor Cells ◽

Viral Infections ◽

Variant Calling ◽

Rna Seq ◽

Major Mechanism ◽

Isoform Diversity ◽

Adar Editing ◽

Transcriptome Diversity

AbstractBackgroundAs the number of RNA-seq datasets that become available to explore transcriptome diversity increases, so does the need for easy-to-use comprehensive computational workflows. Many available tools facilitate analyses of one of the two major mechanisms of transcriptome diversity, namely, differential expression of isoforms due to alternative splicing, while the second major mechanism - RNA editing due to post-transcriptional changes of individual nucleotides – remains under-appreciated. Both these mechanisms play an essential role in physiological and diseases processes, including cancer and neurological disorders. However, elucidation of RNA editing events at transcriptome-wide level requires increasingly complex computational tools, in turn resulting in a steep entrance barrier for labs who are interested in high-throughput variant calling applications on a large scale but lack the manpower and/or computational expertise.ResultsHere we present an easy-to-use, fully automated, computational pipeline (Automated Isoform Diversity Detector, AIDD) that contains open source tools for various tasks needed to map transcriptome diversity, including RNA editing events. To facilitate reproducibility and avoid system dependencies, the pipeline is contained within a pre-configured VirtualBox environment. The analytical tasks and format conversions are accomplished via a set of automated scripts that enable the user to go from a set of raw data, such as fastq files, to publication-ready results and figures in one step. A publicly available dataset of Zika virus-infected neural progenitor cells is used to illustrate AIDD’s capabilities.ConclusionsAIDD pipeline offers a user-friendly interface for comprehensive and reproducible RNA-seq analyses. Among unique features of AIDD are its ability to infer RNA editing patterns, including ADAR editing, and inclusion of Guttman scale patterns for time series analysis of such editing landscapes. AIDD-based results show importance of diversity of ADAR isoforms, key RNA editing enzymes linked with the innate immune system and viral infections. These findings offer insights into the potential role of ADAR editing dysregulation in the disease mechanisms, including those of congenital Zika syndrome. Because of its automated all-inclusive features, AIDD pipeline enables even a novice user to easily explore common mechanisms of transcriptome diversity, including RNA editing landscapes.

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Primary and Repeated Respiratory Viral Infections Among Infants in Rural Nepal

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piy107 ◽

2018 ◽

Vol 9 (1) ◽

pp. 21-29 ◽

Cited By ~ 2

Author(s):

Jim Boonyaratanakornkit ◽

Janet A Englund ◽

Amalia S Magaret ◽

Yunqi Bu ◽

James M Tielsch ◽

...

Keyword(s):

Primary Infection ◽

Respiratory Virus ◽

Viral Infections ◽

Respiratory Illness ◽

Respiratory Viruses ◽

Repeated Infection ◽

Resource Limited ◽

Respiratory Viral Infections ◽

Repeated Infections ◽

Rural Nepal

Abstract Background Respiratory viruses cause significant morbidity and death in infants; 99% of such deaths occur in resource-limited settings. Risk factors for initial and repeated respiratory viral infections in young infants in resource-limited settings have not been well described. Methods From 2011 to 2014, a birth cohort of infants in rural Nepal was enrolled and followed with weekly household-based active surveillance for respiratory symptoms until 6 months of age. Respiratory illness was defined as having any of the following: fever, cough, wheeze, difficulty breathing, and/or a draining ear. We tested nasal swabs of infants with respiratory illness for multiple respiratory viruses by using a reverse transcription polymerase chain reaction assay. The risk of primary and repeated infections with the same virus was evaluated using Poisson regression. Results Of 3528 infants, 1726 (49%) had a primary infection, and 419 (12%) had a repeated infection. The incidences of respiratory viral infection in infants were 1816 per 1000 person-years for primary infections and 1204 per 1000 person-years for repeated infection with the same virus. Exposure to other children and male sex were each associated with an increased risk for primary infection (risk ratios, 1.13 [95% confidence interval (CI), 1.06–1.20] and 1.14 [95% CI, 1.02–1.27], respectively), whereas higher maternal education was associated with a decreased risk for both primary and repeated infections (risk ratio, 0.96 [95% CI, 0.95–0.98]). The incidence of subsequent infection did not change when previous infection with the same or another respiratory virus occurred. Illness duration and severity were not significantly different in the infants between the first and second episodes for any respiratory virus tested. Conclusions In infants in rural Nepal, repeated respiratory virus infections were frequent, and we found no decrease in illness severity with repeated infections and no evidence of replacement with another virus. Vaccine strategies and public health interventions that provide durable protection in the first 6 months of life could decrease the burden of repeated infections by multiple respiratory viruses, particularly in low-resource countries.

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Effect of Nedocromil Sodium on Aspecific Bronchial Hyper-Reactivity in Asthmatic Children

Mediators of Inflammation ◽

10.1155/s096293519400075x ◽

1994 ◽

Vol 3 (7) ◽

pp. S43-S47 ◽

Cited By ~ 2

Author(s):

A. Fiocchi ◽

P. Signoroni ◽

P. Bruni ◽

M. Galeone ◽

E. DeCet ◽

...

Keyword(s):

Viral Infections ◽

Tertiary Care ◽

Nedocromil Sodium ◽

Atmospheric Pollutants ◽

Double Blind Study ◽

Double Blind ◽

Ultrasonic Nebulization ◽

Asthmatic Children ◽

Parallel Group ◽

Perennial Allergens

The purpose of this study was to evaluate whether nedocromil sodium benefits urban asthmatic children showing seasonal bronchial hyper-reactivity to ultrasonic nebulization of distilled water (UNDW). A prospective, randomized, placebo-controlled, parallel-group, double-blind study was carried out at the outpatient pulmonology service at a tertiary-care teaching hospital. Twelve children living in Milan, who were 7–17 years of age, who were SPT and RAST-negative to perennial allergens, who were suffering from episodic asthma, and showing seasonal bronchial hyper-reactivity to UNDW during winter, participated in this study. All the children received either placebo or nedocromil sodium, 4 mg every 6 h for 6 weeks. Spirometry and UNDW challenge were done at the following times: day−7; day 0; day 1; day 7; day 14; day 28; day 42. No differences were found in the basal spirometric parameters, which were normal in both nedocromil and placebo groups. Bronchial reactivity to UNDW was found to be significantly decreased in the group treated with nedocromtl starting from day 7. It is therefore concluded that nedocromil sodium can reverse bronchial hyper-reactivity caused by seasonal factors such as cold, viral infections and atmospheric pollutants in children suffering from asthma.

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Viral infections in outpatients with medically attended acute respiratory illness during the 2012–2013 influenza season

BMC Infectious Diseases ◽

10.1186/s12879-015-0806-2 ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 11

Author(s):

Richard K Zimmerman ◽

Charles R Rinaldo ◽

Mary Patricia Nowalk ◽

GK Balasubramani ◽

Krissy K Moehling ◽

...

Keyword(s):

Viral Infections ◽

Influenza Season ◽

Respiratory Illness ◽

Acute Respiratory Illness

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2854. Enterovirus D68 Infections in Pediatric Patients in Central Ohio: Clinical Characteristics of a New Outbreak in 2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz359.159 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S74-S74

Author(s):

Alejandro Diaz ◽

Huanyu Wang ◽

Isabel Torrus ◽

Fatima Ara Montojo ◽

Maria Mele-Casas ◽

...

Keyword(s):

Clinical Characteristics ◽

Clinical Presentation ◽

Gastrointestinal Symptoms ◽

Respiratory Illness ◽

Neurologic Manifestations ◽

Asthmatic Children ◽

Acute Flaccid Myelitis ◽

Enterovirus D68 ◽

Co Detection ◽

Opsoclonus Myoclonus Syndrome

Abstract Background Many aspects of EV-D68 pathogenesis in children are not fully understood. In 2014, we experienced an outbreak of EV-D68-associated acute respiratory illness affecting mostly asthmatic children with no cases of acute flaccid myelitis identified. Late in 2018, a new outbreak occurred. The objective of this study was to describe the differences in clinical presentation in children diagnosed with EV-D68 infection during the 2018 outbreak. Methods This is a single-center, observational study. Nasopharyngeal (NP) samples from patients <21 years of age that tested positive for rhinovirus/enterovirus (RV/EV) by the FilmArray respiratory panel v1.7 were prospectively collected. EV-D68 was confirmed using a laboratory-developed RT-PCR. Demographic, clinical characteristics, and semiquantitative EV-D68 loads were analyzed according to the clinical presentation. Results From May to October 2018, 1,987/3,633 (55%) samples were RV/EV positive. Of those 399/1,028 (39%) tested positive for EV-D68 (121 outpatients; 278 inpatients). Inpatients were older (3.1 vs. 1.8 year olds; P < 0.01) with no differences in sex or EV-D68 loads (P > 0.05). Within the inpatient cohort, 67 (1.4 year olds) children were previously healthy, 146 (4.1 year olds) had underlying asthma and 65 (2.5 year olds) had chronic medical conditions (24% vs. 53% vs. 23%, respectively). Most patients presented with respiratory symptoms (>95%), followed by fever (51%) or gastrointestinal symptoms (28%). Eleven children (4%) presented with neurologic manifestations including: acute flaccid myelitis in two children, opsoclonus myoclonus syndrome in one child, and seizures in the remaining eight. Rates of viral co-detection were low (8%) and none of the children with neurologic manifestations had another respiratory virus identified. Patients with neurologic findings had lower EV-D68 loads than those who did not (29 vs. 25 Ct values; P = 0.03). Conclusion EV-D68 infection was associated with significant morbidity, affecting children with underlying asthma at greater rates. It was associated with severe neurologic manifestations despite these children having lower EV-D68 loads. Active surveillance for EV-D68 should be routine to allow a better understanding of the epidemiology and severity of disease. Disclosures All Authors: No reported Disclosures.

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Common Microbial Agents in Asthmatic Children With Respiratory Infection and Productive Cough

10.21203/rs.3.rs-96020/v1 ◽

2020 ◽

Author(s):

Faezeh Sabet ◽

Ali Mirhosseini ◽

Samira Basharkhah ◽

Mehran Mohereri ◽

Fatemeh Sadat Mohammadi ◽

...

Keyword(s):

Bacterial Infections ◽

Viral Infections ◽

Respiratory Infections ◽

Respiratory Pathogens ◽

Asthmatic Children ◽

Pediatric Allergy ◽

Asthma Attack ◽

Microbial Infections ◽

Positive Correlations ◽

Microbial Agents

Abstract BackgroundMicrobes can influence on the development and somehow on triggering of asthma attacks. Therefore, in this study the more significant microbial infections which trigger the attacks in children were evaluated.MethodsA total of 41 nasopharyngeal and oro-pharyengeal swabs were obtained from the Pediatric Allergy Clinic of two educational hospitals, and sent to a Molecular Laboratory for evaluation of 21 bacterial and viral respiratory pathogens using qPCR-TaqMan method.ResultsThe main bacterial infections were S.aur 18/41 (43.9%), S.pneu 16/41 (39%), C.pneu 12 /41 (29.3%), and HIB 17/41 (41.5%) while the most viral infections were and HRSV 3/41 (7.3%) and FluB, HRV, HMPVA.B, HPIV-2,3,4, HcoV-63 and HcoV-229 in 2 cases (4,9%), in asthmatic children. Although, bacterial infections were more common in both gender, the frequency of those agents were statistically difference between girls and boys population (P=0.02). There were positive correlations between S. pneu infection with asthma attack and bronchitis (P= 0.02 and P= 0.001, respectively). Furthermore, a positive correlation was found between AV and RSVA.B infections with allergic rhinitis (P= 0.02 and P= 0.001, respectively).ConclusionIn conclusion, it is more likely that in this region with a population of 6.2 million and more than 25 million tourists, the bacterial respiratory infections, particularly, HIB, S.aur and S. pneu were more common, however, and consistence with other studies HRSV and Flu.B have been dominant viral infections in asthmatic attacks.

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Effects of Atmospheric Pollutants on Children Asthma Outbreaks

The Open Allergy Journal ◽

10.2174/1874838400902010009 ◽

2009 ◽

Vol 2 (1) ◽

pp. 9-15 ◽

Cited By ~ 4

Author(s):

Ben Zion Garty ◽

Evsey Kosman ◽

Eliezer Ganor ◽

Niv Alon ◽

Neta Kibilis ◽

...

Keyword(s):

Negative Correlation ◽

Air Pollutants ◽

Viral Infections ◽

Airborne Pollen ◽

Medical Center ◽

Weather Conditions ◽

Atmospheric Pollutants ◽

Asthmatic Children ◽

School Year ◽

Weather Parameters

The effects of air pollutants, weather conditions, airborne pollen and spores on the incidence of emergency room (ER) visits of children for acute asthma attacks were investigated. One-year retrospective study was done. Data on daily concentrations of air pollutants, airborne allergens and weather conditions were collected and compared with the ER visits of 2431 asthmatic children (age 1-18 years) in the Schneider Medical Center, near Tel Aviv. ER visits of asthmatic children showed a negative correlation with the measured O3 concentrations and with extreme ambient temperatures. A positive correlation was found with high barometric pressure with NO2 and SO2 concentrations. An exceptionally high incidence of ER visits of asthmatic children was observed during September, coinciding with the beginning of the school year. When September was excluded from the annual calculations the correlation between ER visits and environmental factors increased. 49% of the variance of ER visits were explained by O3 alone, 46% by NO2 alone, 54% by O3+NO2, and 31% by weather parameters. 58% of the variation was explained by the combination of air pollutants and weather parameters. Airborne particulates did not show any meaningful correlation with ER visits. The major factors associated with severe asthma attacks were high NO2 and SO2. The negative correlation with O3 implies that at certain concentrations, O3 may have a beneficial effect. The particularly high number of ER visits at the beginning of the school year was presumably associated with an increase in viral infections combined with emotional stresses.

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Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains

Vaccines ◽

10.3390/vaccines7010019 ◽

2019 ◽

Vol 7 (1) ◽

pp. 19

Author(s):

Tomer Israely ◽

Nir Paran ◽

Noam Erez ◽

Lilach Cherry ◽

Hadas Tamir ◽

...

Keyword(s):

Vaccinia Virus ◽

Viral Infections ◽

Adaptive Immune Response ◽

Viral Clearance ◽

Smallpox Vaccination ◽

Cns Infection ◽

Rna Seq ◽

Tissue Integrity ◽

Brain Infection ◽

The Central Nervous System

Viral infections of the central nervous system (CNS) lead to a broad range of pathologies. CNS infections with Orthopox viruses have been mainly documented as an adverse reaction to smallpox vaccination with vaccinia virus. To date, there is insufficient data regarding the mechanisms underlying pathological viral replication or viral clearance. Therefore, informed risk assessment of vaccine adverse reactions or outcome prediction is limited. This work applied a model of viral infection of the CNS, comparing neurovirulent with attenuated strains. We followed various parameters along the disease and correlated viral load, morbidity, and mortality with tissue integrity, innate and adaptive immune response and functionality of the blood–brain barrier. Combining these data with whole brain RNA-seq analysis performed at different time points indicated that neurovirulence is associated with host immune silencing followed by induction of tissue damage-specific pathways. In contrast, brain infection with attenuated strains resulted in rapid and robust induction of innate and adaptive protective immunity, followed by viral clearance and recovery. This study significantly improves our understanding of the mechanisms and processes determining the consequence of viral CNS infection and highlights potential biomarkers associated with such outcomes.

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