Blood mRNA profiling to support prognosis of disease severity in respiratory syncytial virus infected infants
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Arno Andeweg
PROVIDER: E-MTAB-5195 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:To study the transcriptional profile of patients with acute RSV or Influenza infection,children of median age 2.4 months (range 1.5-8.6) hospitalized with acute RSV and influenza virus infection were offered study enrollment after microbiologic confirmation of the diagnosis. Blood samples were collected from them within 42-72 hours of hospitalization. We excluded children with suspected or proven polymicrobial infections, with underlying chronic medical conditions (i.e congenital heart disease, renal insufficiency), with immunodeficiency, or those who received systemic steroids or other immunomodulatory therapies. The RSV cohort consisted of 51 patients with median age of 2 months (range 1.5-3.9) and the influenza cohort had 28 patients with median age of 5.5 months (range 1.4-21). Control samples were obtained from healthy children undergoing elective surgical procedures or at outpatient clinic visits. To exclude viral co-infections we performed nasopharyngeal viral cultures of all subjects. We recruited 10 control patients for the RSV cohort with median age of 6.7 months (range 5-10), and 12 control patients for the influenza cohort with median age of18.5 months (range 10.5-26). We used microarrays to obtain the transcriptional profile of PBMCs from patients with acute RSV or Influenza infection and compared these signatures with the transcriptional profile of primary airway epithelial cells infected with RSV or Influenza.
2012-03-12 | E-GEOD-34205 | biostudies-arrayexpress
Project description:Cell transformation by the Src tyrosine kinase is characterized by extensive changes in gene expression. To describe these changes, investigators have relied extensively on the study of immortalized rodent cell lines or heterogeneous tumor samples that limit the identification of differentially expressed genes or may not represent the full spectrum of biological processes regulated during transformation. In this study, we took advantage of transformation-deficient and temperature sensitive mutants of the Rous sarcoma virus to characterize the patterns of gene expression in two types of primary cells, namely chicken embryo fibroblasts (CEF) and chicken neuro-retinal (CNR) cells. Keywords: viral transformation of primary cells, transformation, transformation deficient mutant, temperature sensitive mutant, v-Src Chicken embryo fibroblasts (CEF) were infected with the wild-type strain Schmidt-Ruppin A RSV or non-transforming strain NY315 RSV or the non-transforming control virus RCASBP(A) to assess genes involved in v-Src-dependent transformation of CEF. Chicken embryo fibroblasts (CEF) were infected with the temperature sensitve strain NY72-4 RSV and cultured either at non-permissive temperature (41.5M-KM-^ZC) or permissive temperature (37M-KM-^ZC) to assess genes involved in v-Src-dependent transformation of CEF. Chicken neuroretina cells (CNR) were infected with the temperature sensitve strain NY72-4 RSV and cultured either at non-permissive temperature (41.5M-KM-^ZC) or permissive temperature (37M-KM-^ZC) to assess genes involved in v-Src-dependent transformation of CNR and compared to CEF.
2010-02-21 | E-GEOD-14489 | biostudies-arrayexpress
Project description:While the majority of infants infected with respiratory syncytial virus (RSV) exhibit mild or no symptoms, approximately 3 million children under the age of five are hospitalized every year due to complications from RSV. This research sought to explore the biological processes and related biomarkers responsible for the varied manifestations of RSV disease in young infants. The goal is to pave the way for a more precise categorization of RSV-infected infants based on their medical requirements. Whole blood samples are collected from infant case-control cohort study, the RESCEU case-control cohort is a multinational, multicenter, observational study (clinical trial registration number: NCT03756766). Infants < 12 months old with RSV disease were recruited from the University Medical Center Utrecht (UMCU) in The Netherlands, Hospital Clínico Universitario de Santiago (SERGAS) in Spain, Imperial College (IMPERIAL) National Health Service Trust (NHS) and Oxford University Hospital NHS Trust (OXFORD) in the United Kingdom during the RSV seasons 2017-2018, 2018-2019, and 2019-2020. Healthy controls without underlying comorbidities were recruited outside of the RSV season. Eligibility criteria included hospitalization for less than 48 hours at enrolment or within 96 hours of disease onset, no previous receipt of medications to treat RSV infection, no prior exposure to an investigational RSV vaccine or medication, no previous receipt of immunoglobulins or monoclonal antibodies, and had not used montelukast or oral steroids within seven days before enrolment. Infants with co-morbidities were not evaluated in the manuscript. RSV was detected using RSV point-of-care test (POCT) by either a rapid antigen detection test (Alere I) (Alere Inc, Waltham, Massachusetts) or rapid RSV polymerase chain reaction (PCR) test at the hospital setting, or a RSV PCR test at the laboratory. Convalescence samples were collected 7 ±1 weeks after a positive RSV diagnostic test result. We used microarray to assist us to identify biomarkers for severe RSV disease.
2024-01-03 | GSE246622 | GEO
Project description:Background: There is limited data on how different RSV genotypes and associated viral loads influence disease phenotypes. We characterized the genetic variability of RSV strains during five non-consecutive respiratory seasons, and evaluated the role of RSV subtypes, genotypes and viral loads on clinical disease severity. Methods: Healthy infants hospitalized with RSV bronchiolitis were prospectively enrolled and nasopharyngeal samples obtained within 24h of hospitalization for RSV load quantitation by PCR, typing and genotyping. Parameters of disease severity were assessed, and multivariate models constructed to identify virologic and clinical factors predictive of clinical outcomes. Results: From March 2004 to April 2011, we enrolled 253 patients (56.5 % males; median age 2.1 (1.1-4.0) months). RSV A infections predominated over RSV B (69% vs. 31%; p<0.001) and showed greater genotype variability. The most common genotypes were RSV A/GA2, A/GA5 and RSV B/BA. Infants infected with RSV GA5 had higher viral loads compared with GA2 or BA infection (p<0.01), independent of duration of symptoms. After adjusting for other covariates, RSV A/GA5 infections were associated with longer hospital stay. Conclusions: RSV A infections were more frequent than RSV B infections and displayed greater genetic variability. Infections with GA5 were independently associated with clinical disease severity.
2018-03-21 | GSE103842 | GEO
Project description:To investigate how human airway epithelial cells respond to Influenza or RSV infection, we harvested airway epithelial cells from the mainstream bronchi of human donors and cultured them as previously described (Pickles et al,1998) in a polarized system that resembles the in vivo mucociliary pseudostratified epithelium. Quadruplicate hAEC cultures were infected with 2X105 PFUs Influenza A (Udorn) or with 1x106 PFUs RSV for 2h or mock inoculated and harvested 24h after Influenza infection and 48h after RSV infection. Quadruplicate polarized airway epithelial cell cultures were infected with 2x10^5 PFUs of Influenza A (Udorn) for 2h or infected with 1x10^6 PFUs RSV and harvested 24 h post infection for Influenza or 48h post infection for RSV.Duplicate cultures were used as controls for each condition (Two cultures were mock treated mor 2h and harvested after 24h for the Influenza infection and 2 cultures were mock treated for 2h and harvested after 48 hours for the RSV infection.Total RNA was harvested and gene expression was studied using Genespring GX v7.3.1.
2012-03-12 | E-GEOD-32139 | biostudies-arrayexpress
Project description:Human respiratory syncytial virus (RSV) is the leading cause of severe acute lower respiratory tract infections in infants worldwide. Non-structural protein NS1 of RSV modulates the host innate immune response by acting as an antagonist of type I and type III interferon (IFN) production and signaling in multiple ways. It is likely that NS1 performs this function by interacting with different host proteins. In order to obtain a comprehensive overview of NS1 interaction partners, we performed three complementary protein-protein interaction screens i.e. BioID, MAPPIT and KISS. The BioID proximity screen was performed during an RSV infection in A549 cells. MED25, a subunit of the Mediator complex, was identified in all 3 performed screening methods as a potential NS1 interacting protein. We confirmed the interaction between MED25 and RSV NS1 by co-immunoprecipitation, not only upon overexpression of NS1, but also with endogenous NS1 during RSV infection. We also demonstrate that the replication of RSV is enhanced in MED25 knockout A549 cells, suggesting a potential antiviral role of MED25 during RSV infection. Mediator subunits function as transcriptional coactivators and are involved in transcriptional regulation of their target genes. Therefore, the interaction between RSV NS1 and cellular MED25 might be beneficial during an RSV infection as this can affect host transcription and the host immune response to infection.
2022-09-09 | PXD034627 | Pride
Project description:To investigate how human airway epithelial cells respond to Influenza or RSV infection, we harvested airway epithelial cells from the mainstream bronchi of human donors and cultured them as previously described (Pickles et al,1998) in a polarized system that resembles the in vivo mucociliary pseudostratified epithelium. Quadruplicate hAEC cultures were infected with 2X105 PFUs Influenza A (Udorn) or with 1x106 PFUs RSV for 2h or mock inoculated and harvested 24h after Influenza infection and 48h after RSV infection. Quadruplicate polarized airway epithelial cell cultures were mock treated or infected with 2x10^5 PFUs of Influenza A (Udorn) for 2h or infected with 1x10^6 PFUs RSV and harvested 24 h post infection for Influenza or 48h post infection for RSV. Total RNA was harvested and gene expression was studied using Genespring GX v7.3.1.
2012-03-12 | E-GEOD-32138 | biostudies-arrayexpress
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