Abstract
Human respiratory syncytial virus (HRSV) is the main cause of bronchiolitis during the first year of life, when infections by other viruses, such as rhinovirus, also occur and are clinically indistinguishable from those caused by HRSV. In hospitalized infants with bronchiolitis, the analysis of gene expression profiles from peripheral blood mononuclear cells (PBMC) may be useful for the rapid identification of etiological factors, as well as for developing diagnostic tests, and elucidating pathogenic mechanisms triggered by different viral agents. In this study we conducted a comparative global gene expression analysis of PBMC obtained from two groups of infants with acute viral bronchiolitis who were infected by HRSV (HRSV group) or by HRV (HRV group). We employed a weighted gene co-expression network analysis (WGCNA) which allows the identification of transcriptional modules and their correlations with HRSV or HRV groups. This approach permitted the identification of distinct transcription modules for the HRSV and HRV groups. According to these data, the immune response to HRSV infection—comparatively to HRV infection—was more associated to the activation of the interferon gamma signaling pathways and less related to neutrophil activation mechanisms. Moreover, we also identified host-response molecular markers that could be used for etiopathogenic diagnosis. These results may contribute to the development of new tests for respiratory virus identification. The finding that distinct transcriptional profiles are associated to specific host responses to HRSV or to HRV may also contribute to the elucidation of the pathogenic mechanisms triggered by different respiratory viruses, paving the way for new therapeutic strategies.
Highlights
Viral bronchiolitis is frequent and has an important impact on the children’s health care due to the high rates of hospitalization and mortality, especially of young infants [1, 2]
The current guidelines do not indicate routine tests to identify the etiologic agent in infants with bronchiolitis, the etiological diagnosis may contribute to the prevention of nosocomial acquisition, since the transmission mechanisms diverge among respiratory viruses
In the Human respiratory syncytial virus (HRSV) group most of the differentially expressed (DE) genes (204 genes) were hyper-expressed and only 79 genes were hypo-expressed when compared with the human rhinovirus (HRV) group
Summary
Viral bronchiolitis is frequent and has an important impact on the children’s health care due to the high rates of hospitalization and mortality, especially of young infants [1, 2]. Human respiratory syncytial virus (HRSV) is the predominant etiological agent, but infections by other respiratory viruses, such as human rhinovirus (HRV), metapneumovirus, parainfluenza, influenza, adenovirus, and coronavirus, occur. These infections with different respiratory virus present similar clinical characteristics, so etiological diagnosis can be carried out in clinical practice only by virus identification, either by molecular tests, immunofluorescence or culture methods [1,2,3,4,5]. The current guidelines do not indicate routine tests to identify the etiologic agent in infants with bronchiolitis, the etiological diagnosis may contribute to the prevention of nosocomial acquisition, since the transmission mechanisms diverge among respiratory viruses. Etiological diagnosis may contribute for developing specific therapeutic approaches for each agent
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