{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:38:46Z","timestamp":1782535126092,"version":"3.54.5"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pediatr"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections in children, especially bronchiolitis. Our study aimed to identify the key genes and upstream transcription factors in RSV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To screen for RSV pathogenic genes, an integrated analysis was performed using the RSV microarray dataset in GEO. Functional annotation and potential pathways for differentially expressed genes (DEGs) were further explored by GO and KEGG enrichment analysis. We constructed the RSV-specific transcriptional regulatory network to identify key transcription factors for DEGs in RSV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From three GEO datasets, we identified 1059 DEGs (493 up-regulated and 566 down-regulated genes, FDR\u2009&lt;\u20090.05 and |Combined.ES|\u2009&gt;\u20090.8) between RSV patients and normal controls. GO and KEGG analysis revealed that \u2018response to virus\u2019 (FDR\u2009=\u20097.13E-15), \u2018mitochondrion\u2019 (FDR\u2009=\u20091.39E-14) and \u2018Asthma\u2019 (FDR\u2009=\u20091.28E-06) were significantly enriched pathways for DEGs. The expression of IFI27, IFI44, IFITM3, FCER1A, and ISG15 were shown to be involved in the pathogenesis of RSV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We concluded that IFI27, IFI44, IFITM3, FCER1A, and ISG15 may play a role in RSV. Our finding may contribute to the development of new potential biomarkers, reveal the underlying pathogenesis and also identify novel therapeutic targets for RSV.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12887-020-02480-4","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T19:04:52Z","timestamp":1610132692000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Identification of pathogenic genes and transcription factors in respiratory syncytial virus"],"prefix":"10.1186","volume":"21","author":[{"given":"Lei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong An","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenfeng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"issue":"24","key":"2480_CR1","doi-asserted-by":"publisher","first-page":"13810","DOI":"10.1128\/JVI.02571-12","volume":"86","author":"WJ Lee","year":"2012","unstructured":"Lee WJ, Kim YJ, Kim DW, Lee HS, Lee HY, Kim K. Complete genome sequence of human respiratory syncytial virus genotype a with a 72-nucleotide duplication in the attachment protein G gene. J Virol. 2012;86(24):13810\u20131.","journal-title":"J Virol"},{"key":"2480_CR2","unstructured":"Zhang Y, Zhuochao L. Analysis of clinical characteristics and therapy in respiratory syncytial virus acute lower respiratory infection. J Pediatr Pharmacy. 2015;21(12):15-9."},{"key":"2480_CR3","unstructured":"Arguedasflatts YN, Capistr\u00e1n MA, Christen JA, Noyola DE. An analysis of the interaction between influenza and respiratory syncytial virus based on acute respiratory infection records. arXiv e-prints. 2013:arXiv:1312.0594."},{"issue":"1","key":"2480_CR4","doi-asserted-by":"publisher","first-page":"81","DOI":"10.4149\/av_2011_01_81","volume":"55","author":"E Faghihloo","year":"2011","unstructured":"Faghihloo E, Rezaie F, Salimi V, Naseri M, Mamishi S, Mahmoodi M, et al. Molecular epidemiology of human respiratory syncytial virus in Iran. Acta Virol. 2011;55(1):81\u20133.","journal-title":"Acta Virol"},{"issue":"2","key":"2480_CR5","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1164\/rccm.200406-730OC","volume":"171","author":"N Sigurs","year":"2005","unstructured":"Sigurs N, Gustafsson PM, Bjarnason R, Lundberg F, Schmidt S, Sigurbergsson F, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med. 2005;171(2):137\u201341.","journal-title":"Am J Respir Crit Care Med"},{"issue":"11","key":"2480_CR6","doi-asserted-by":"publisher","first-page":"5654","DOI":"10.1128\/JVI.76.11.5654-5666.2002","volume":"76","author":"L Zhang","year":"2002","unstructured":"Zhang L, Peeples ME, Boucher RC, Collins PL, Pickles RJ. Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology. J Virol. 2002;76(11):5654\u201366.","journal-title":"J Virol"},{"issue":"9","key":"2480_CR7","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1164\/rccm.201602-0220OC","volume":"194","author":"WA de Steenhuijsen Piters","year":"2016","unstructured":"de Steenhuijsen Piters WA, Heinonen S, Hasrat R, Bunsow E, Smith B, Suarez-Arrabal MC, et al. Nasopharyngeal microbiota, host Transcriptome, and disease severity in children with respiratory syncytial virus infection. Am J Respir Crit Care Med. 2016;194(9):1104\u201315.","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"2480_CR8","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1067\/mpd.2000.110531","volume":"137","author":"TG Boyce","year":"2000","unstructured":"Boyce TG, Mellen BG, Mitchel EF Jr, Wright PF, Griffin MR. Rates of hospitalization for respiratory syncytial virus infection among children in medicaid. J Pediatr. 2000;137(6):865\u201370.","journal-title":"J Pediatr"},{"issue":"6","key":"2480_CR9","doi-asserted-by":"publisher","first-page":"e1453","DOI":"10.1542\/peds.2010-0507","volume":"126","author":"CG Garcia","year":"2010","unstructured":"Garcia CG, Bhore R, Soriano-Fallas A, Trost M, Chason R, Ramilo O, et al. Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis. Pediatrics. 2010;126(6):e1453\u201360.","journal-title":"Pediatrics."},{"issue":"9","key":"2480_CR10","doi-asserted-by":"publisher","first-page":"2405","DOI":"10.1007\/s00705-018-3881-z","volume":"163","author":"N Madi","year":"2018","unstructured":"Madi N, Chehadeh W, Asadzadeh M, Al-Turab M, Al-Adwani A. Analysis of genetic variability of respiratory syncytial virus groups a and B in Kuwait. Arch Virol. 2018;163(9):2405\u201313.","journal-title":"Arch Virol"},{"issue":"1","key":"2480_CR11","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1089\/jir.2010.0105","volume":"31","author":"V Cheriyath","year":"2011","unstructured":"Cheriyath V, Leaman DW, Borden EC. Emerging roles of FAM14 family members (G1P3\/ISG 6-16 and ISG12\/IFI27) in innate immunity and cancer. J Interferon Cytokine Res. 2011;31(1):173\u201381.","journal-title":"J Interferon Cytokine Res"},{"issue":"22","key":"2480_CR12","doi-asserted-by":"publisher","first-page":"5947","DOI":"10.1046\/j.0014-2956.2001.02545.x","volume":"268","author":"PM Martensen","year":"2001","unstructured":"Martensen PM, Sogaard TM, Gjermandsen IM, Buttenschon HN, Rossing AB, Bonnevie-Nielsen V, et al. The interferon alpha induced protein ISG12 is localized to the nuclear membrane. Eur J Biochem. 2001;268(22):5947\u201354.","journal-title":"Eur J Biochem"},{"issue":"1","key":"2480_CR13","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1471-2164-5-8","volume":"5","author":"N Parker","year":"2004","unstructured":"Parker N, Porter AC. Identification of a novel gene family that includes the interferon-inducible human genes 6-16 and ISG12. BMC Genomics. 2004;5(1):8.","journal-title":"BMC Genomics"},{"issue":"4","key":"2480_CR14","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1007\/s10495-008-0190-0","volume":"13","author":"S Rosebeck","year":"2008","unstructured":"Rosebeck S, Leaman DW. Mitochondrial localization and pro-apoptotic effects of the interferon-inducible protein ISG12a. Apoptosis. 2008;13(4):562\u201372.","journal-title":"Apoptosis"},{"issue":"3","key":"2480_CR15","doi-asserted-by":"publisher","first-page":"216","DOI":"10.3109\/09513590.2011.588746","volume":"28","author":"A Mihalich","year":"2012","unstructured":"Mihalich A, Vigano P, Gentilini D, Borghi MO, Vignali M, Busacca M, et al. Interferon-inducible genes, TNF-related apoptosis-inducing ligand (TRAIL) and interferon inducible protein 27 (IFI27) are negatively regulated in leiomyomas: implications for a role of the interferon pathway in leiomyoma development. Gynecol Endocrinol. 2012;28(3):216\u20139.","journal-title":"Gynecol Endocrinol"},{"issue":"2","key":"2480_CR16","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/cpr.12168","volume":"48","author":"WL Hsieh","year":"2015","unstructured":"Hsieh WL, Huang YH, Wang TM, Ming YC, Tsai CN, Pang JH. IFI27, a novel epidermal growth factor-stabilized protein, is functionally involved in proliferation and cell cycling of human epidermal keratinocytes. Cell Prolif. 2015;48(2):187\u201397.","journal-title":"Cell Prolif"},{"issue":"1","key":"2480_CR17","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.jss.2014.06.055","volume":"193","author":"S Li","year":"2015","unstructured":"Li S, Xie Y, Zhang W, Gao J, Wang M, Zheng G, et al. Interferon alpha-inducible protein 27 promotes epithelial-mesenchymal transition and induces ovarian tumorigenicity and stemness. J Surg Res. 2015;193(1):255\u201364.","journal-title":"J Surg Res"},{"issue":"22","key":"2480_CR18","doi-asserted-by":"publisher","first-page":"11688","DOI":"10.1128\/JVI.76.22.11688-11703.2002","volume":"76","author":"L Labrada","year":"2002","unstructured":"Labrada L, Liang XH, Zheng W, Johnston C, Levine B. Age-dependent resistance to lethal alphavirus encephalitis in mice: analysis of gene expression in the central nervous system and identification of a novel interferon-inducible protective gene, mouse ISG12. J Virol. 2002;76(22):11688\u2013703.","journal-title":"J Virol"},{"key":"2480_CR19","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/1471-2334-6-175","volume":"6","author":"HO Fjaerli","year":"2006","unstructured":"Fjaerli HO, Bukholm G, Krog A, Skjaeret C, Holden M, Nakstad B. Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis. BMC Infect Dis. 2006;6:175.","journal-title":"BMC Infect Dis"},{"issue":"8","key":"2480_CR20","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1089\/jir.2007.0021","volume":"27","author":"LC Hallen","year":"2007","unstructured":"Hallen LC, Burki Y, Ebeling M, Broger C, Siegrist F, Oroszlan-Szovik K, et al. Antiproliferative activity of the human IFN-alpha-inducible protein IFI44. J Interferon Cytokine Res. 2007;27(8):675\u201380.","journal-title":"J Interferon Cytokine Res"},{"issue":"4","key":"2480_CR21","doi-asserted-by":"publisher","first-page":"4650","DOI":"10.3892\/mmr.2017.7150","volume":"16","author":"JG Hu","year":"2017","unstructured":"Hu JG, Fu Y, Xu JJ, Ding XP, Xie HQ, Li-Ling J. Altered gene expression profile in a rat model of gentamicin-induced ototoxicity and nephrotoxicity, and the potential role of upregulated Ifi44 expression. Mol Med Rep. 2017;16(4):4650\u20138.","journal-title":"Mol Med Rep"},{"issue":"3","key":"2480_CR22","doi-asserted-by":"publisher","first-page":"e00051","DOI":"10.1128\/mSystems.00051-16","volume":"1","author":"JU McDonald","year":"2016","unstructured":"McDonald JU, Kaforou M, Clare S, Hale C, Ivanova M, Huntley D, et al. A simple screening approach to prioritize genes for functional analysis identifies a role for interferon regulatory factor 7 in the control of respiratory syncytial virus disease. mSystems. 2016;1(3):e00051.","journal-title":"mSystems"},{"issue":"45","key":"2480_CR23","doi-asserted-by":"publisher","first-page":"32184","DOI":"10.1074\/jbc.M113.514356","volume":"288","author":"CC Bailey","year":"2013","unstructured":"Bailey CC, Kondur HR, Huang IC, Farzan M. Interferon-induced transmembrane protein 3 is a type II transmembrane protein. J Biol Chem. 2013;288(45):32184\u201393.","journal-title":"J Biol Chem"},{"issue":"11","key":"2480_CR24","doi-asserted-by":"publisher","first-page":"e80723","DOI":"10.1371\/journal.pone.0080723","volume":"8","author":"AR Everitt","year":"2013","unstructured":"Everitt AR, Clare S, McDonald JU, Kane L, Harcourt K, Ahras M, et al. Defining the range of pathogens susceptible to Ifitm3 restriction using a knockout mouse model. PLoS One. 2013;8(11):e80723.","journal-title":"PLoS One"},{"issue":"11","key":"2480_CR25","doi-asserted-by":"crossref","first-page":"6166","DOI":"10.4049\/jimmunol.151.11.6166","volume":"151","author":"J Pang","year":"1993","unstructured":"Pang J, Taylor GR, Munroe DG, Ishaque A, Fung-Leung WP, Lau CY, et al. Characterization of the gene for the human high affinity IgE receptor (Fc epsilon RI) alpha-chain. J Immunol (Baltimore, Md : 1950). 1993;151(11):6166\u201374.","journal-title":"J Immunol (Baltimore, Md : 1950)"},{"issue":"1","key":"2480_CR26","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1177\/0300985814520639","volume":"52","author":"CJ Knudson","year":"2015","unstructured":"Knudson CJ, Varga SM. The relationship between respiratory syncytial virus and asthma. Vet Pathol. 2015;52(1):97\u2013106.","journal-title":"Vet Pathol"},{"issue":"9","key":"2480_CR27","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/ncb1038","volume":"5","author":"CA Sledz","year":"2003","unstructured":"Sledz CA, Holko M, de Veer MJ, Silverman RH, Williams BR. Activation of the interferon system by short-interfering RNAs. Nat Cell Biol. 2003;5(9):834\u20139.","journal-title":"Nat Cell Biol"},{"issue":"7","key":"2480_CR28","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nri2314","volume":"8","author":"AJ Sadler","year":"2008","unstructured":"Sadler AJ, Williams BR. Interferon-inducible antiviral effectors. Nat Rev Immunol. 2008;8(7):559\u201368.","journal-title":"Nat Rev Immunol"},{"issue":"25","key":"2480_CR29","doi-asserted-by":"publisher","first-page":"11657","DOI":"10.1073\/pnas.92.25.11657","volume":"92","author":"WC Au","year":"1995","unstructured":"Au WC, Moore PA, Lowther W, Juang YT, Pitha PM. Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes. Proc Natl Acad Sci U S A. 1995;92(25):11657\u201361.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"2480_CR30","doi-asserted-by":"publisher","first-page":"3428","DOI":"10.1128\/JVI.02695-15","volume":"90","author":"R Gonzalez-Sanz","year":"2016","unstructured":"Gonzalez-Sanz R, Mata M, Bermejo-Martin J, Alvarez A, Cortijo J, Melero JA, et al. ISG15 is Upregulated in respiratory syncytial virus infection and reduces virus growth through protein ISGylation. J Virol. 2016;90(7):3428\u201338.","journal-title":"J Virol"}],"container-title":["BMC Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-020-02480-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12887-020-02480-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-020-02480-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T07:10:40Z","timestamp":1697526640000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpediatr.biomedcentral.com\/articles\/10.1186\/s12887-020-02480-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2480"],"URL":"https:\/\/doi.org\/10.1186\/s12887-020-02480-4","relation":{},"ISSN":["1471-2431"],"issn-type":[{"value":"1471-2431","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,8]]},"assertion":[{"value":"6 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"We obtained the written informed consent from every parent or guardian for participants under 16\u2009years old and the approval from the ethics committee of the Affiliated Hospital of Qingdao University (QYFYW2LL25724).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"27"}}