Análisis de la expresión de la diana 3 alfa de la metiltransferasa de ADN durante la infección por el virus sincitial...

Respiratory syncytial virus (RSV) is a seasonal pathogen known to cause lower respiratory tract infections, including bronchiolitis and pneumonia, and it is associated with an increased risk of developing asthma and recurrent wheezing in pediatric populations. Epigenetic mechanisms, such as DNA methylation and histone modifications, have been implicated in regulating host immune responses during viral infections. In this study, we investigated DNMT3A expression, a de novo DNA methyltransferase, during RSV infection. We queried the Gene Expression Omnibus (GEO) database for RNA-sequencing datasets related to RSV infection. Among the five relevant datasets identified, one demonstrated significantly elevated DNMT3A expression in RSV-infected samples compared to controls. To validate and further examine this finding, we infected MRC-5 cells, a human lung fibroblast cell line, with RSV-A strain (RSV-A2) and accessed DNMT3A expression at different time points using real-time RT-qPCR. We observed an upregulation of DNMT3A expression at 8 h post-infection; this induction was decreased in the presence of rapamycin, an inhibitor of the mTOR pathway. Immunofluorescence analysis confirms DNMT3A presence in RSV-infected cells. In vivo analysis revealed a significant increase in Dnmt3a expression in murine lung tissue five days following RSV infection. In ex-vivo RSV-infected pediatric lung tissue sample the DNMT3A gene expression was not increase compared to uninfected tissue. Our findings suggest that RSV modulates DNMT3A expression through mTOR pathway, but this effect is transient and dependent on the sample and the kinetics of infection. Our data highlights a potential epigenetic mechanism involved in the gene expression regulation of the host during infection.