Portal de Periódicos da CAPES

Whole Exome Sequencing reveals new candidate genes in host genomic susceptibility to Respiratory Syncytial Virus Disease

2017; Nature Portfolio; Volume: 7; Issue: 1 Linguagem: Inglês

10.1038/s41598-017-15752-4

2045-2322

Antonio Salas, Jacobo Pardo‐Seco, Miriam Cebey‐López, Alberto Gómez‐Carballa, Pablo Obando-Pacheco, Irene Rivero‐Calle, María José Currás-Tuala, Jorge Amigo, José Gómez Rial, Federico Martinón‐Torres, Antonio José Justicia-Grande, Beatriz Morillo-Gutiérrez, Lorenzo Redondo-Collazo, Carmen Rodrı́guez-Tenreiro, Ruth Barral‐Arca, Sara Pischedda, José Peña-Guitián, Carmen Curros Novo, Miriam Puente-Puig, Rosaura Leis, Federico Martinón‐Torres, José María Martinón‐Sánchez, Máximo Fraga, José Ramón Antúnez López, Enrique Bernaola-Iturbe, Laura Moreno‐Galarraga, Jorge Álvarez, Teresa González-López, Delfina Suarez-Vázquez, Ángela Vázquez Vázquez, Susana Rey-García, Francisco Giménez‐Sánchez, Miguel Forte, Cristina Calvo, María Luz García‐García, Ignacio Oulego-Erróz, David Vivas, Santiago Lapeña, Paula Alonso‐Quintela, Jorge Martínez-Sáenz de Jubera, Estibaliz Garrido-García, Cristina Calvo Monge, Eider Oñate-Vergara, Jesús de la Cruz Moreno, María del Carmen Martínez‐Padilla, Manuel Baca-Cots, David Moreno‐Pérez, Susana Beatriz-Reyes, María Cruz León-León,

RNA and protein synthesis mechanisms

Abstract Respiratory syncytial virus (RSV) is an important cause of serious lower respiratory tract disease in infants. Several studies have shown evidence pointing to the genome of the host as an important factor determining susceptibility to respiratory disease caused by RSV. We sequenced the complete exomes of 54 patients infected by RSV that needed hospitalization due to development of severe bronchiolitis. The Iberian sample (IBS) from The 1000 Genomes Project (1000G) was used as control group; all the association results were pseudo-replicated using other 1000G-European controls and Spanish controls. The study points to SNP rs199665292 in the olfactory receptor (OR) gene OR13C5 as the best candidate variant ( P -value = 1.16 × 10 −12 ; OR = 5.56). Genetic variants at HLA genes ( HLA-DQA1 , HLA-DPB1 ), and in the mucin 4 gene ( MUC4 ) also emerge as susceptibility candidates. By collapsing rare variants in genes and weighing by pathogenicity, we obtained confirmatory signals of association in the OR gene OR8U1 / OR8U8 , the taste receptor TAS2R19 , and another mucin gene ( MUC6 ). Overall, we identified new predisposition variants and genes related to RSV infection. Of special interest is the association of RSV to olfactory and taste receptors; this finding is in line with recent evidence pointing to their role in viral infectious diseases.