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Background <p>Respiratory syncytial virus (RSV) poses significant morbidity and mortality risks in childhood, particularly for previously healthy infants admitted to hospitals lacking predisposing risk factors for severe disease. This study aimed to investigate the role of the host epigenome in RSV infection severity using non-invasive buccal swabs from sixteen hospitalized infants admitted to the hospital for RSV infection. Eight patients had severe symptoms, and eight had mild to moderate symptoms. For DNA methylation analyses, the Illumina EPIC BeadChip was used with DNA isolated from saliva samples. To evaluate the basal DNA methylation level of the identified biomarkers a cohort of healthy control children was used. Furthermore, DNA methylation levels of candidate genes were confirmed by pyrosequencing in both the discovery and validation cohorts of patients with mild to moderate symptoms.</p> Results <p>A panel of differentially methylated positions (DMPs) distinguishing severe from mild to moderate symptoms in infants was identified. DMPs were determined using a threshold of an adjusted <i>P</i>-value (false discovery rate, FDR) &lt; 0.01 and an absolute difference in DNA methylation (delta beta) &gt; 0.10. Differentially methylated regions (DMRs) were identified in the <i>ZBTB38</i> (implicated in asthma and pulmonary disease) and the <i>TRIM6-TRM34</i> gene region (associated with viral infections). The differential DNA methylation of these genes was validated in an independent replication cohort. A weighted correlation network analysis emphasized the pivotal role of a module with <i>RAB11FIP5</i> as the hub gene, known for its critical function in regulating viral infections.</p> Conclusions <p>Oral mucosa methylation may play a role in determining the severity of RSV disease in infants.</p>

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DNA methylation signatures of severe RSV infection in infants: evidence from non-invasive saliva samples

  • 期刊论文

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  • 发表日期：

    2025年4月28日

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  • Sara Pischedda,
  • Alberto Gómez-Carballa,
  • Jacobo Pardo-Seco,
  • Sandra Viz-Lasheras,
  • Alba Camino-Mera,
  • Xabier Bello,
  • María José Curras-Tuala,
  • Irene Rivero-Calle,
  • Ana I. Dacosta-Urbieta,
  • Federico Martinón-Torres,
  • Antonio Salas,
  • Miriam Cebey López,
  • Ana Vega Gliemmo,
  • José Peña Guitián,
  • Carmen Curros Novo,
  • Rosaura Leis Trabazo,
  • Nazareth Martinón Torres,
  • José María Martinón Sánchez,
  • Belén Mosquera Pérez,
  • Lorenzo Redondo Collazo,
  • Carmen Rodríguez-Tenreiro,
  • Miriam Taboada Puga,
  • Ana Cotovad Bellas,
  • Ana María Pastoriza Morelle,
  • Silvia Cerqueiro Rey,
  • Sara Rey Vázquez,
  • Ana María Senín Ferreiro,
  • Sonia Serén Fernández,
  • Maria Soledad Vilas Iglesias,
  • Mirian Ben García,
  • Patricia Regueiro Casuso,
  • Lara Martinez Martinez,
  • Máximo Francisco Fraga Rodríguez,
  • Orlando Fernández Lago,
  • José Ramón Antúnez,
  • Carmen Martínez Padilla,
  • Jesús de la CruzMoreno,
  • Eugenia Villanueva Martínez,
  • Ana González Espín,
  • María de las Mercedes Martínez Rebollo,
  • María Rocío Martín Moya,
  • M. Victoria Ramos Casado,
  • Pablo Rojo,
  • Palacios Cuesta Alba,
  • Francisco Javier Pilar Orive,
  • Carla Pintos Tubert,
  • Diego García Urabayen,
  • Esteban Gomez Sanchez,
  • Juan Valencia Ramos,
  • Jesús López-Herce,
  • Débora Sanz Alvarez,
  • Cristina Calvo,
  • Sonia Alcolea,
  • Rocio Sánchez,
  • Jorge Atucha,
  • Jara Hurtado,
  • Ana López Fernández,
  • Clara Gil González,
  • Teresa González López,
  • Delfina Suarez Vázquez,
  • Ángela Vázquez Vázquez,
  • Susana Rey García,
  • Nathalie Carreira Sande,
  • Nuria Romero Pérez,
  • Diego Bautista Lozano,
  • Alcaraz Romero Andres Jose,
  • Sara Guillen Martin,
  • Ana Pérez Aragón,
  • Catalina Ortiz Paredes,
  • María Teresa Rives Ferreiro,
  • Jose Luis Moreno Salgado,
  • Olalla Moyano Leiva,
  • Carla Taboada Rubinos,
  • Ana Capilla Miranda,
  • Jorge Contreras,
  • Andrés Concha Torre,
  • Elena del Castillo Navío,
  • Ana Grande Tejada,
  • Alfredo Tagarro García,
  • María Luisa Herreros,
  • Rut del Valle,
  • Laura Moreno Galarraga,
  • Enrique Bernaola Iturbe,
  • Jorge Álvarez,
  • Mercedes Herranz,
  • Francisco Gil,
  • Eva Gembero,
  • Jorge Rodríguez,
  • María Luz García García,
  • Cristina Calvo Rey,
  • Iciar Olabarrieta Arnal,
  • Adelaida Fernández Rincón,
  • Susana Beatriz Reyes,
  • María Cruz León León,
  • Santiago Alfayate,
  • Beatriz Mercader,
  • Francisco Giménez Sánchez,
  • Elvira González Salas,
  • Sira Fernández De Miguel,
  • Alfredo Tagarro García,
  • María Concepción Zazo Sanchidrián,
  • Esteban García-Fontecha,
  • Marta González Lorenzo,
  • Mariano Esteban,
  • María Carmen Vicent Castello,
  • Lorena Moreno Requena,
  • César Gavilán Martín,
  • Monterrat López Franco,
  • Mª Nieves Glez Bravo,
  • María Jesús Cabero,
  • Marta Pareja,
  • Adriana Navas Carretero,
  • Elvira Cobo Vazquez,
  • Patricia Flores Perez,
  • María Yolanda Ruiz del Prado,
  • José Antonio Couceiro Gianzo,
  • Nazareth Fuentes Perez,
  • Roi Piñeiro,
  • Belen Joyanes Abancens,
  • Carlos Rodrigo Gonzalo de Liria,
  • Maria Méndez,
  • Francisco Giménez Sánchez,
  • Miguel Sánchez Forte,
  • María José Cilleruelo Ortega,
  • Luz Golmayo,
  • Francisca Portero Azorín

摘要

Background

Respiratory syncytial virus (RSV) poses significant morbidity and mortality risks in childhood, particularly for previously healthy infants admitted to hospitals lacking predisposing risk factors for severe disease. This study aimed to investigate the role of the host epigenome in RSV infection severity using non-invasive buccal swabs from sixteen hospitalized infants admitted to the hospital for RSV infection. Eight patients had severe symptoms, and eight had mild to moderate symptoms. For DNA methylation analyses, the Illumina EPIC BeadChip was used with DNA isolated from saliva samples. To evaluate the basal DNA methylation level of the identified biomarkers a cohort of healthy control children was used. Furthermore, DNA methylation levels of candidate genes were confirmed by pyrosequencing in both the discovery and validation cohorts of patients with mild to moderate symptoms.

Results

A panel of differentially methylated positions (DMPs) distinguishing severe from mild to moderate symptoms in infants was identified. DMPs were determined using a threshold of an adjusted P-value (false discovery rate, FDR) < 0.01 and an absolute difference in DNA methylation (delta beta) > 0.10. Differentially methylated regions (DMRs) were identified in the ZBTB38 (implicated in asthma and pulmonary disease) and the TRIM6-TRM34 gene region (associated with viral infections). The differential DNA methylation of these genes was validated in an independent replication cohort. A weighted correlation network analysis emphasized the pivotal role of a module with RAB11FIP5 as the hub gene, known for its critical function in regulating viral infections.

Conclusions

Oral mucosa methylation may play a role in determining the severity of RSV disease in infants.