{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:12:35Z","timestamp":1792707155493,"version":"4.5.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Human respiratory syncytial virus (RSV) is one of the main viral agents associated with the development of acute respiratory infections (ARIs), particularly during infancy and early childhood. RSV vaccine have recently been approved, however, are currently limited to older adults and pregnant women, with no approval for young children. In the absence of broadly effective and accessible preventive or therapeutic options for this vulnerable population, understanding the biology of RSV represents a critical alternative strategy. While several viral proteins have been reported to regulate the expression of interferon-stimulated genes (ISGs) to evade the host antiviral immune response, recent studies have shown that some viruses can also recruit host cellular proteins to facilitate their replication or modulate antiviral pathways. In this context, the nucleolus, and its resident proteins, such as fibrillarin (FBL), have been suggested to play a role in the regulation of inflammatory responses and in the activation of genes involved in early antiviral defense mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To analyze FBL expression under viral infection conditions, immunofluorescence assays (IFA) and Western blot (WB) analyses were performed. The effects of FBL depletion were evaluated using WB, IFA, RT-qPCR, and lytic plaque assays. Three experimental conditions were established: uninfected A549 cells (mock), RSV-infected cells, and RSV-infected cells with FBL knockdown. To determine the relationship between FBL and interferon-stimulated gene (ISG) expression, RT-qPCR assays were performed to quantify the expression levels of selected ISGs, including OAS1, OAS2, IFIT3, PKR, and RIG-I. Additionally, FBL-knockdown cells were transfected with a GFP-FBL construct to restore FBL expression, and the recovery of RSV infection was evaluated by IFA, RT-qPCR, and plaque-forming unit (PFU) assays. Moreover, the downregulation of ISG expression in cells with restored GFP-FBL was assessed by RT-qPCR. Finally, p53 knockdown assays were performed to evaluate changes in FBL expression and the reduction of RSV infection, as determined by WB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RSV infection was found to induce FBL expression at early stages of infection in A549 cells. Additionally, our data suggest that FBL suppresses the expression of interferon-stimulated genes (ISGs). Conversely, silencing of FBL significantly reduced RSV infection. Importantly, this reduction in viral replication was associated with increased ISG expression in FBL-deficient A549 cells upon RSV infection. Furthermore, exogenous expression of FBL in FBL-knockdown cells restored RSV infection and led to a concomitant reduction in ISG expression following the recovery of FBL protein levels. Finally, p53-knockdown cells reduced viral protein M2\u20131 levels without affecting FBL expression, pointing to the involvement of other regulatory mechanism controlling FBL during RSV infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data show that RSV infection promotes the expression of the FBL protein, creating an environment devoid of early antiviral response mediators such as ISGS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1706028","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:44:18Z","timestamp":1776231858000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Human respiratory syncytial virus regulates the expression of interferon-stimulated genes through modulation of fibrillarin"],"prefix":"10.3389","volume":"16","author":[{"given":"Jos\u00e9 Manuel","family":"Ulloa-Aguilar","sequence":"first","affiliation":[{"name":"Laboratorio de Virolog\u00eda Perinatal y Dise\u00f1o Molecular de Antigenos y Biomarcadores, Departamento de Inmunobioquimica, Instituto Nacional de Perinatolog\u00eda","place":["Mexico City, Mexico"]},{"name":"Posgrado en Biolog\u00eda Experimental, Divsi\u00f3n de Ciencias biologicas y de la Salud (DCBS), Universidad Aut\u00f3noma Metropolitana- Iztapalapa","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Javier","family":"Cruz-Holguin","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Perinatal y Dise\u00f1o Molecular de Antigenos y Biomarcadores, Departamento de Inmunobioquimica, Instituto Nacional de Perinatolog\u00eda","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazm\u00edn Roc\u00edo","family":"Ben\u00edtez-Zeferino","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Perinatal y Dise\u00f1o Molecular de Antigenos y Biomarcadores, Departamento de Inmunobioquimica, Instituto Nacional de Perinatolog\u00eda","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar Rodrigo","family":"Guzm\u00e1n-Bautista","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sobre la Salud P\u00fablica, Universidad de la Sierra Sur, Miahuatlan de Porfirio D\u00edaz","place":["Oaxaca, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Garc\u00eda-Cordero","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina Molecular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional (CINVESTAV-IPN)","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Adri\u00e1n","family":"De Jes\u00fas-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n Biom\u00e9dica de Zacatecas, Instituto Mexicano del Seguro Social","place":["Zacatecas, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio Angel","family":"V\u00e1zquez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Immunology, H. 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