Gene Signature of Children with Severe Respiratory Syncytial Virus Infection

Overview

Journal Pediatr Res

Specialties Biology
Pediatrics

Date 2021 Jan 29

PMID 33510411

Citations 9

Authors

Clyde Dapat

Satoru Kumaki

Hiroki Sakurai

Hidekazu Nishimura

Hannah Karen Mina Labayo

Michiko Okamoto

Mayuko Saito

Hitoshi Oshitani

Affiliations

Soon will be listed here.

Abstract

Background: The limited treatment options for children with severe respiratory syncytial virus (RSV) infection highlights the need for a comprehensive understanding of the host cellular response during infection. We aimed to identify host genes that are associated with severe RSV disease and to identify drugs that can be repurposed for the treatment of severe RSV infection.

Methods: We examined clinical data and blood samples from 37 hospitalized children (29 mild and 8 severe) with RSV infection. We tested RNA from blood samples using next-generation sequencing to profile global mRNA expression and identify cellular processes.

Results: Retractions, decreased breath sounds, and tachypnea were associated with disease severity. We observed upregulation of genes related to neutrophil, inflammatory response, blood coagulation, and downregulation of genes related to T cell response in children with severe RSV. Using network-based approach, 43 drugs were identified that are predicted to interact with the gene products of these differentially expressed genes.

Conclusions: These results suggest that the changes in the expression pattern in the innate and adaptive immune responses may be associated with RSV clinical severity. Compounds that target these cellular processes can be repositioned as candidate drugs in the treatment of severe RSV.

Impact: Neutrophil, inflammation, and blood coagulation genes are upregulated in children with severe RSV infection. Expression of T cell response genes are suppressed in cases of severe RSV. Genes identified in this study can contribute in understanding the pathogenesis of RSV disease severity. Drugs that target cellular processes associated with severe RSV can be repositioned as potential therapeutic options.

Citing Articles

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections.

Lydon E, Osborne C, Wagner B, Ambroggio L, Harris J, Reeder R mSystems. 2024; 10(1):e0133524.

PMID: 39611811 PMC: 11748518. DOI: 10.1128/msystems.01335-24.

Hyperexpression of and as Possible Platelet Risk Biomarkers in Patients With COVID-19.

DE Oliveira Sales L, DA Silva J, DE Pinho Pessoa F, Dias Nogueira B, DE Oliveira L, Khayat A In Vivo. 2024; 38(6):2853-2863.

PMID: 39477442 PMC: 11535951. DOI: 10.21873/invivo.13766.

IL-1α is required for T cell-driven weight loss after respiratory viral infection.

Wang Z, Cuthbertson L, Thomas C, Sallah H, Mosscrop L, Li H Mucosal Immunol. 2024; 17(2):272-287.

PMID: 38382577 PMC: 11009121. DOI: 10.1016/j.mucimm.2024.02.005.

Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing.

Fitzpatrick A, Mohammad A, Huang M, Stephenson S, Patrignani J, Kamaleswaran R J Allergy Clin Immunol. 2023; 152(6):1433-1443.

PMID: 37604313 PMC: 10841272. DOI: 10.1016/j.jaci.2023.08.010.

Early peripheral blood MCEMP1 and HLA-DRA expression predicts COVID-19 prognosis.

Chan K, Koh C, Ng D, Qin S, Ooi J, Ong E EBioMedicine. 2023; 89:104472.

PMID: 36801619 PMC: 9934388. DOI: 10.1016/j.ebiom.2023.104472.

References

Shi T, McAllister D, OBrien K, Simoes E, Madhi S, Gessner B . Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. 2017; 390(10098):946-958. PMC: 5592248. DOI: 10.1016/S0140-6736(17)30938-8. View

Nair H, Nokes D, Gessner B, Dherani M, Madhi S, Singleton R . Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010; 375(9725):1545-55. PMC: 2864404. DOI: 10.1016/S0140-6736(10)60206-1. View

Janssen R, Pennings J, Hodemaekers H, Buisman A, van Oosten M, de Rond L . Host transcription profiles upon primary respiratory syncytial virus infection. J Virol. 2007; 81(11):5958-67. PMC: 1900269. DOI: 10.1128/JVI.02220-06. View

Martinez I, Lombardia L, Garcia-Barreno B, Dominguez O, Melero J . Distinct gene subsets are induced at different time points after human respiratory syncytial virus infection of A549 cells. J Gen Virol. 2007; 88(Pt 2):570-581. DOI: 10.1099/vir.0.82187-0. View

Hastie M, Headlam M, Patel N, Bukreyev A, Buchholz U, Dave K . The human respiratory syncytial virus nonstructural protein 1 regulates type I and type II interferon pathways. Mol Cell Proteomics. 2012; 11(5):108-27. PMC: 3418853. DOI: 10.1074/mcp.M111.015909. View

Mejias A, Dimo B, Suarez N, Garcia C, Suarez-Arrabal M, Jartti T . Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection. PLoS Med. 2013; 10(11):e1001549. PMC: 3825655. DOI: 10.1371/journal.pmed.1001549. View

Brand H, Ahout I, De Ridder D, van Diepen A, Li Y, Zaalberg M . Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection. PLoS One. 2015; 10(7):e0131927. PMC: 4498630. DOI: 10.1371/journal.pone.0131927. View

Modjarrad K, Giersing B, Kaslow D, Smith P, Moorthy V . WHO consultation on Respiratory Syncytial Virus Vaccine Development Report from a World Health Organization Meeting held on 23-24 March 2015. Vaccine. 2015; 34(2):190-197. PMC: 6858870. DOI: 10.1016/j.vaccine.2015.05.093. View

10.

Okamoto M, Dapat C, Sandagon A, Batangan-Nacion L, Lirio I, Tamaki R . Molecular Characterization of Respiratory Syncytial Virus in Children With Repeated Infections With Subgroup B in the Philippines. J Infect Dis. 2018; 218(7):1045-1053. PMC: 6107742. DOI: 10.1093/infdis/jiy256. View

11.

Malasao R, Okamoto M, Chaimongkol N, Imamura T, Tohma K, Dapat I . Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013. PLoS One. 2015; 10(11):e0142192. PMC: 4635013. DOI: 10.1371/journal.pone.0142192. View

12.

Beccuti M, Cordero F, Arigoni M, Panero R, Amparore E, Donatelli S . SeqBox: RNAseq/ChIPseq reproducible analysis on a consumer game computer. Bioinformatics. 2017; 34(5):871-872. PMC: 6030956. DOI: 10.1093/bioinformatics/btx674. View

13.

Jiang H, Lei R, Ding S, Zhu S . Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired-end reads. BMC Bioinformatics. 2014; 15:182. PMC: 4074385. DOI: 10.1186/1471-2105-15-182. View

14.

Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S . STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2012; 29(1):15-21. PMC: 3530905. DOI: 10.1093/bioinformatics/bts635. View

15.

Marini F, Binder H . pcaExplorer: an R/Bioconductor package for interacting with RNA-seq principal components. BMC Bioinformatics. 2019; 20(1):331. PMC: 6567655. DOI: 10.1186/s12859-019-2879-1. View

16.

Anders S, Huber W . Differential expression analysis for sequence count data. Genome Biol. 2010; 11(10):R106. PMC: 3218662. DOI: 10.1186/gb-2010-11-10-r106. View

17.

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

18.

Leek J, Johnson W, Parker H, Jaffe A, Storey J . The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012; 28(6):882-3. PMC: 3307112. DOI: 10.1093/bioinformatics/bts034. View

19.

Ignatiadis N, Klaus B, Zaugg J, Huber W . Data-driven hypothesis weighting increases detection power in genome-scale multiple testing. Nat Methods. 2016; 13(7):577-80. PMC: 4930141. DOI: 10.1038/nmeth.3885. View

20.

Ashburner M, Ball C, Blake J, Botstein D, Butler H, Cherry J . Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000; 25(1):25-9. PMC: 3037419. DOI: 10.1038/75556. View

21.

Kanehisa M, Goto S . KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999; 28(1):27-30. PMC: 102409. DOI: 10.1093/nar/28.1.27. View